Enhancing mango yield and soil health with organic and slow-release fertilizers: A multifaceted evaluation.

Excessive utilization of chemical fertilizers in mango orchards not only hampers the attainment of sustainable harvests but also poses significant ecological detriments. This investigation proposes a promising solution by advocating the judicious replacement of chemical fertilizers with organic fertilizer (OF) and slow-release fertilizer (SRF), with potential to bolster soil health and augment crop productivity. In light of the promise held by these alternatives, it is imperative to establish detailed fertilization protocols for enhanced sustainable practices in mango farming. This two-year field study employed a comprehensive suite of seven fertilization strategies, unveiling that a 25 % chemical fertilizers substitution with OF and SRF improved mango yields by 12.5 % and 11.3 %, respectively, over standard practices. Additionally, these approaches substantially augmented the nutritional quality of mangoes, evident from Vitamin C enhancements of 53.9 % to 56.9 %, and improvements in sugar-to-acid ratio (19.2 %-30.3 %) and solid-to-acid ratio (12.1 %-25.3 %). Notably, the application of OF and SRF led to increased leaf nitrogen and phosphorus concentrations, while simultaneously reducing soil phosphorus and potassium levels. Furthermore, these fertilizers fostered the growth of beneficial soil microorganisms, namely Actinobacteria and Proteobacteria, and strengthened the synergy within the soil bacterial community, hence optimizing bacterial competition and nutrient cycling. The study proposes that the adoption of OF or SRF can effectively regulate soil nutrient balance, promote resilient and functional soil bacterial ecosystems, and ultimately improve mango yield and fruit quality. It recommends a fertilization scheme incorporating 25 % organic or slow-release nitrogen to align with ecological sustainability goals, promoting a more vigorous and resilient soil and crop system.

Identification of habitat suitability for the dominant zoonotic tick species Haemaphysalis flava on Chongming Island, China.

Haemaphysalis ticks are pathogenic vectors that threaten human and animal health and were identified in Chongming, the third largest island in China. To understand the distribution of these ticks and determine their potential invasion risk, this study aimed to identify the habitat suitability of the dominant tick H. flava based on natural environmental factors. Geographic information system (GIS) images were combined with sample points from tick investigations to map the spatial distribution of H. flava. Data on 19 bioclimatic variables, environmental variables, and satellite-based landscapes of Chongming Island were retrieved to create a landcover map related to natural environmental determinants of H. flava. These data included 38 sites associated with the vectors to construct species distribution models with MaxEnt, a model based on the maximum entropy principle, and to predict habitat suitability for H. flava on Chongming Island in 2050 and 2070 under different climate scenarios. The model performed well in predicting the H. flava distribution, with a training area under the curve of 0.84 and a test area under the curve of 0.73. A habitat suitability map of the whole study area was created for H. flava. The resulting map and natural environment analysis highlighted the importance of the normalized difference vegetation index and precipitation in the driest month for the bioecology of H. flava, with 141.61 km2 (11.77%), 282.94 km2 (23.35%), and 405.30 km2 (33.69%) of highly, moderately, and poorly suitable habitats, respectively. The distribution decreased by 135.55 km2 and 138.82 km2 in 2050 and 2070, respectively, under the shared socioeconomic pathway (SSP) 1.2.6 climate change scenario. However, under SSP 5.8.5, the total area will decrease by 128.5 km2 in 2050 and increase by 151.64 km2 in 2070. From a One Health perspective, this study provides good knowledge that will guide tick control efforts to prevent the spread of Haemaphysalis ticks or transmission risk of Haemaphysalis-borne infections at the human-animal-environment interface on the island.

Targeting astrocytic TDAG8 with delayed CO2 postconditioning improves functional outcomes after controlled cortical impact injury in mice.

T-cell death-associated gene 8 (TDAG8), a G-protein-coupled receptor sensing physiological or weak acids, regulates inflammatory responses. However, its role in traumatic brain injury (TBI) remains unknown. Our recent study showed that delayed CO2 postconditioning (DCPC) has neuroreparative effects after TBI. We hypothesized that activating astrocytic TDAG8 is a key mechanism for DCPC. WT and TDAG8-/- mice received DCPC daily by transiently inhaling 10% CO2 after controlled cortical impact (CCI). HBAAV2/9-GFAP-m-TDAG8-3xflag-EGFP was used to overexpress TDAG8 in astrocytes. The beam walking test, mNSS, immunofluorescence and Golgi-Cox staining were used to evaluate motor function, glial activation and dendritic plasticity. DCPC significantly improved motor function; increased total dendritic length, neuronal complexity and spine density; inhibited overactivation of astrocytes and microglia; and promoted the expression of astrocytic brain-derived neurotrophic factor in WT but not TDAG8-/- mice. Overexpressing TDAG8 in astrocytes surrounding the lesion in TDAG8-/- mice restored the beneficial effects of DCPC. Although the effects of DCPC on Days 14-28 were much weaker than those of DCPC on Days 3-28 in WT mice, these effects were further enhanced by overexpressing astrocytic TDAG8. Astrocytic TDAG8 is a key target of DCPC for TBI rehabilitation. Its overexpression is a strategy that broadens the therapeutic window and enhances the effects of DCPC.

A Prognostic Model Incorporating Relevant Peripheral Blood Inflammation Indicator to Predict Postherpetic Neuralgia in Patients with Acute Herpes Zoster.

Objective: To determine the risk of postherpetic neuralgia (PHN) in patients with acute herpes zoster (HZ), this study developed and validated a novel clinical prediction model by incorporating a relevant peripheral blood inflammation indicator. Methods: Between January 2019 and June 2023, 209 patients with acute HZ were categorized into the PHN group (n = 62) and the non-PHN group (n = 147). Univariate and multivariate logistic regression analyses were conducted to identify risk factors serving as independent predictors of PHN development. Subsequently, a nomogram prediction model was established, and the discriminative ability and calibration were evaluated using the receiver operating characteristic curve, calibration plots, and decision curve analysis (DCA). The nomogram model was internally verified through the bootstrap test method. Results: According to univariate logistic regression analyses, five variables, namely age, hypertension, acute phase Numeric Rating Scale (NRS-11) score, platelet-to-lymphocyte ratio (PLR), and systemic immune inflammation index, were significantly associated with PHN development. Multifactorial analysis further unveiled that age (odds ratio (OR) [95% confidence interval (CI)]: 2.309 [1.163-4.660]), acute phase NRS-11 score (OR [95% CI]: 2.837 [1.294-6.275]), and PLR (OR [95% CI]: 1.015 [1.010-1.022]) were independent risk factors for PHN. These three predictors were integrated to establish the prediction model and construct the nomogram. The area under the receiver operating characteristic curve (AUC) for predicting the PHN risk was 0.787, and the AUC of internal validation determined using the bootstrap method was 0.776. The DCA and calibration curve also indicated that the predictive performance of the nomogram model was commendable. Conclusion: In this study, a risk prediction model was developed and validated to accurately forecast the probability of PHN after HZ, thereby demonstrating favorable discrimination, calibration, and clinical applicability.

The bacterial and fungal profiles of patients hospitalized with non-COVID-19 lower respiratory tract infections in Wuhan, China, 2019-2021.

AIMS: A severe lockdown occurred in Wuhan during the COVID-19 pandemic, followed by a remission phase in the pandemic's aftermath. This study analyzed the bacterial and fungal profiles of respiratory pathogens in patients hospitalized with non-COVID-19 lower respiratory tract infections (LRTIs) during this period to determine the pathogen profile distributions in different age groups and hospital departments in Wuhan. METHODS AND RESULTS: We collected reports of pathogen testing in the medical records of patients hospitalized with non-COVID-19 LRTI between 2019 and 2021. These cases were tested for bacterial and fungal pathogens using 16S and internal transcribed spacer sequencing methods on bronchoalveolar lavage fluid samples. The study included 1368 cases. The bacteria most commonly identified were Streptococcus pneumoniae (12.50%) and Mycoplasma pneumoniae (8.33%). The most commonly identified fungi were Aspergillus fumigatus (2.49%) and Pneumocystis jirovecii (1.75%). Compared to 2019, the S. pneumoniae detection rates increased significantly in 2021, and those of M. pneumoniae decreased. Streptococcus pneumoniae was detected mainly in children. The detection rates of almost all fungi were greater in the respiratory Intensive Care Unit compared to respiratory medicine. Streptococcus pneumoniae and M. pneumoniae were detected more frequently in the pediatric department. CONCLUSIONS: Before and after the COVID-19 outbreak, a change in the common pathogen spectrum was detected in patients with non-COVID-19 in Wuhan, with the greatest change occurring among children. The major pathogens varied by the patient's age and the hospital department.

Targeting Neuronal GPR65 With Delayed BTB09089 Treatment Improves Neurorehabilitation Following Ischemic Stroke.

BACKGROUND: GPR65 (G protein-coupled receptor 65) can sense extracellular acidic environment to regulate pathophysiological processes. Pretreatment with the GPR65 agonist BTB09089 has been proven to produce neuroprotection in acute ischemic stroke. However, whether delayed BTB09089 treatment and neuronal GPR65 activation promote neurorestoration remains unknown. METHODS: Ischemic stroke was induced in wild-type (WT) or GPR65 knockout (GPR65-/-) mice by photothrombotic ischemia. Male mice were injected intraperitoneally with BTB09089 every other day at days 3, 7, or 14 poststroke. AAV-Syn-GPR65 (adenoassociated virus-synapsin-GPR65) was utilized to overexpress GPR65 in the peri-infarct cortical neurons of GPR65-/- and WT mice. Motor function was monitored by grid-walk and cylinder tests. The neurorestorative effects of BTB09089 were observed by immunohistochemistry, Golgi-Cox staining, and Western blotting. RESULTS: BTB09089 significantly promoted motor outcomes in WT but not in GPR65-/- mice, even when BTB09089 was delayed for 3 to 7 days. BTB09089 inhibited the activation of microglia and glial scar progression in WT but not in GPR65-/- mice. Meanwhile, BTB09089 reduced the decrease in neuronal density in WT mice, but this benefit was abolished in GPR65-/- mice and reemerged by overexpressing GPR65 in peri-infarct cortical neurons. Furthermore, BTB09089 increased the GAP43 (growth-associated protein-43) and synaptophysin puncta density, dendritic spine density, dendritic branch length, and dendritic complexity by overexpressing GPR65 in the peri-infarct cortical neurons of GPR65-/- mice, which was accompanied by increased levels of p-CREB (phosphorylated cAMP-responsive element-binding protein). In addition, the therapeutic window of BTB09089 was extended to day 14 by overexpressing GPR65 in the peri-infarct cortical neurons of WT mice. CONCLUSIONS: Our findings indicated that delayed BTB09089 treatment improved neurological functional recovery and brain tissue repair poststroke through activating neuronal GRP65. GPR65 overexpression may be a potential strategy to expand the therapeutic time window of GPR65 agonists for neurorehabilitation after ischemic stroke.

A TrmBL2-like transcription factor mediates the growth phase-dependent expression of halolysin SptA in a concentration-dependent manner in Natrinema gari J7-2.

To cope with a high-salinity environment, haloarchaea generally employ the twin-arginine translocation (Tat) pathway to transport secretory proteins across the cytoplasm membrane in a folded state, including Tat-dependent extracellular subtilases (halolysins) capable of autocatalytic activation. Some halolysins, such as SptA of Natrinema gari J7-2, are produced at late-log phase to prevent premature enzyme activation and proteolytic damage of cellular proteins in haloarchaea; however, the regulation mechanism for growth phase-dependent expression of halolysins remains largely unknown. In this study, a DNA-protein pull-down assay was performed to identify the proteins binding to the 5'-flanking sequence of sptA encoding halolysin SptA in strain J7-2, revealing a TrmBL2-like transcription factor (NgTrmBL2). The ΔtrmBL2 mutant of strain J7-2 showed a sharp decrease in the production of SptA, suggesting that NgTrmBL2 positively regulates sptA expression. The purified recombinant NgTrmBL2 mainly existed as a dimer although monomeric and higher-order oligomeric forms were detected by native-PAGE analysis. The results of electrophoretic mobility shift assays (EMSAs) showed that NgTrmBL2 binds to the 5'-flanking sequence of sptA in a non-specific and concentration-dependent manner and exhibits an increased DNA-binding affinity with the increase in KCl concentration. Moreover, we found that a distal cis-regulatory element embedded in the neighboring upstream gene negatively regulates trmBL2 expression and thus participates in the growth phase-dependent biosynthesis of halolysin SptA. IMPORTANCE: Extracellular proteases play important roles in nutrient metabolism, processing of functional proteins, and antagonism of haloarchaea, but no transcription factor involved in regulating the expression of haloaechaeal extracellular protease has been reported yet. Here we report that a TrmBL2-like transcription factor (NgTrmBL2) mediates the growth phase-dependent expression of an extracellular protease, halolysin SptA, of haloarchaeon Natrinema gari J7-2. In contrast to its hyperthermophilic archaeal homologs, which are generally considered to be global transcription repressors, NgTrmBL2 functions as a positive regulator for sptA expression. This study provides new clues about the transcriptional regulation mechanism of extracellular protease in haloarchaea and the functional diversity of archaeal TrmBL2.

Neighborhood Disadvantage and Prostate Tumor RNA Expression of Stress-Related Genes.

Importance: African American men experience greater prostate cancer incidence and mortality than White men. Growing literature supports associations of neighborhood disadvantage, which disproportionately affects African American men, with aggressive prostate cancer; chronic stress and downstream biological impacts (eg, increased inflammation) may contribute to these associations. Objective: To examine whether several neighborhood disadvantage metrics are associated with prostate tumor RNA expression of stress-related genes. Design, Setting, and Participants: This cross-sectional study leveraged prostate tumor transcriptomic data for African American and White men with prostate cancer who received radical prostatectomy at the University of Maryland Medical Center between August 1992 and January 2021. Data were analyzed from May 2023 to April 2024. Exposures: Using addresses at diagnosis, 2 neighborhood deprivation metrics (Area Deprivation Index [ADI] and validated bayesian Neighborhood Deprivation Index) as well as the Racial Isolation Index (RI) and historical redlining were applied to participants' addresses. Self-reported race was determined using electronic medical records. Main Outcomes and Measures: A total of 105 stress-related genes were evaluated with each neighborhood metric using linear regression, adjusting for race, age, and year of surgery. Genes in the Conserved Transcriptional Response to Adversity (CTRA) and stress-related signaling genes were included. Results: A total of 218 men (168 [77%] African American, 50 [23%] White) with a median (IQR) age of 58 (53-63) years were included. African American participants experienced greater neighborhood disadvantage than White participants (median [IQR] ADI, 115 [100-130] vs 92 [83-104]; median [IQR] RI, 0.68 [0.34-0.87] vs 0.11 [0.06-0.14]). ADI was positively associated with expression for 11 genes; HTR6 (serotonin pathway) remained significant after multiple-comparison adjustment (ß = 0.003; SE, 0.001; P < .001; Benjamini-Hochberg q value = .01). Several genes, including HTR6, were associated with multiple metrics. We observed higher expression of 5 proinflammatory genes in the CTRA with greater neighborhood disadvantage (eg, CXCL8 and ADI, ß = 0.008; SE, 0.003; P = .01; q value = .21). Conclusions and Relevance: In this cross-sectional study, the expression of several stress-related genes in prostate tumors was higher among men residing in disadvantaged neighborhoods. This study is one of the first to suggest associations of neighborhood disadvantage with prostate tumor RNA expression. Additional research is needed in larger studies to replicate findings and further investigate interrelationships of neighborhood factors, tumor biology, and aggressive prostate cancer to inform interventions to reduce disparities.

Effect of konjac glucomannan-based preservation pads on quality changes in refrigerated large yellow croaker (Pseudosciaena crocea).

The purpose of this study was to evaluate the preservation effects of konjac glucomannan (KGM)/oregano essential oil (OEO) Pickering emulsion-based pads (K/OPE pads) on large yellow croaker (Pseudosciaena crocea) fillets stored at 4 °C. The K/OPE pads were fabricated using a freeze-drying technique. The homogeneous distribution of the OEO Pickering emulsions in the KGM matrix was observed using scanning electron microscopy. Fourier transform infrared spectroscopy confirmed that the OEO emulsions were encapsulated in the KGM and there was hydrogen bonding interaction between them. Compared with the KGM pads, the K/OPE pad groups demonstrated enhanced antioxidant and antimicrobial properties. When the content of OPE was increased from 20 % to 40 %, the antioxidant performance of the K/OPE pads increased from 48.09 % ± 0.03 % to 86.65 % ± 0.02 % and the inhibition range of Escherichia coli and Staphylococcus aureus increased to 13.84 ± 0.81 and 16.87 ± 1.53 mm, respectively. At the same time, K/OPE pads were more effective in inhibiting the formation of total volatile alkaline nitrogen and the production of thiobarbituric acid-reactive substances, thereby helping in reducing water loss and maintaining the muscle tissue structure of fish fillets for a longer storage time. Consequently, these K/OPE40 pads extended the shelf life of the fish fillets by an additional 4 days and delayed spoilage during refrigerated storage. The findings suggest that the K/OPE pads can effectively safeguard the quality of refrigerated large yellow croaker fillets, presenting their potential as an active packaging material in the fish preservation industry.

Photocatalytic Reduction of Perrhenate and Pertechnetate in a Strongly Acidic Aqueous Solution.

Pertechnetate (99TcO4-), a physiologically toxic radioactive anion, is of great concern due to its high mobility in environmental contamination remediation. Although the soluble oxyanion can be photoreduced to sparingly soluble TcO2·nH2O, its effective removal from a strongly acidic aqueous solution remains a challenge. Here, we found that low-crystalline nitrogen-doped titanium oxide (N-TiO2, 0.6 g L-1) could effectively uptake perrhenate (ReO4-, 10 mg L-1, a nonradioactive surrogate for TcO4-) with 50.8% during 360 min under simulated sunlight irradiation at pH 1.0, but P25 and anatase could not. The nitrogen active center formed by trace nitrogen doping in N-TiO2 can promote the separation and transfer of photogenerated carriers. The positive valence band value of N-TiO2 is slightly higher than those of P25 and anatase, which means that the photogenerated holes have a stronger oxidizability. These holes are involved in the formation of strong reducing •CO2- radicals from formic acid oxidation. The active radicals convert ReO4- to Re(VI), which is subsequently disproportionated to Re(IV) and Re(VII). Effective photocatalytic reduction/removal of Re(VII)/Tc(VII) is performed on the material, which may be considered a potential and convenient strategy for technetium decontamination and extraction in a strongly acidic aqueous solution.

Significant Differences in Intestinal Bacterial Communities of Sympatric Bean Goose, Hooded Crane, and Domestic Goose.

The host's physiological well-being is intricately associated with the gut microbiota. However, previous studies regarding the intestinal microbiota have focused on domesticated or captive birds. This study used high-throughput sequencing technology to identify the gut bacterial communities of sympatric bean geese, hooded cranes, and domestic geese. The results indicated that the gut bacterial diversity in domestic geese and hooded cranes showed considerably higher diversity than bean geese. The gut bacterial community compositions varied significantly among the three hosts (p < 0.05). Compared to the hooded crane, the bean goose and domestic goose were more similar in their genotype and evolutionary history, with less difference in the bacterial community composition and assembly processes between the two species. Thus, the results might support the crucial role of host genotypes on their gut microbiota. The gut bacteria of wild hooded cranes and bean geese had a greater capacity for energy metabolism compared to domestic geese, suggesting that wild birds may rely more on their gut microbiota to survive in cold conditions. Moreover, the intestines of the three hosts were identified as harboring potential pathogens. The relative abundance of pathogens was higher in the hooded crane compared to the other two species. The hooded crane gut bacterial community assemblage revealed the least deterministic process with the lowest filtering/selection on the gut microbiota, which might have been a reason for the highest number of pathogens result. Compared to the hooded crane, the sympatric bean goose showed the least diversity and relative abundance of pathogens. The intestinal bacterial co-occurrence network showed the highest stability in the bean goose, potentially enhancing host resistance to adverse environments and reducing the susceptibility to pathogen invasion. In this study, the pathogens were also discovered to overlap among the three hosts, reminding us to monitor the potential for pathogen transmission between poultry and wild birds. Overall, the current findings have the potential to enhance the understanding of gut bacterial and pathogenic community structures in poultry and wild birds.

The etiological diagnostic value of metagenomic next-generation sequencing in suspected community-acquired pneumonia.

BACKGROUND: The emergence of metagenomic next-generation sequencing (mNGS) may provide a promising tool for early and comprehensive identification of the causative pathogen in community-acquired pneumonia (CAP). In this study, we aim to further evaluate the etiological diagnostic value of mNGS in suspected CAP. METHODS: A total of 555 bronchoalveolar lavage fluid (BALF) samples were collected for pathogen detection by mNGS from 541 patients with suspected CAP. The clinical value was assessed based on infection diagnosis and treatment guidance. The diagnostic performance for pathogen identification by mNGS and sputum culture and for tuberculosis (TB) by mNGS and X-pert MTB/RIF were compared. To evaluate the potential for treatment guidance, we analyzed the treatment regimen of patients with suspected CAP, including imaging changes of lung after empirical antibacterial therapy, intensified regimen, antifungal treatment, and a 1-year follow up for patients with unconfirmed diagnosis and non-improvement imaging after anti-infective treatment and patients with high suspicion of TB or NTM infection who were transferred to the Wuhan Pulmonary Hospital for further diagnosis and even anti-mycobacterium therapy. RESULTS: Of the 516 BALF samples that were analyzed by both mNGS and sputum culture, the positivity rate of mNGS was significantly higher than that of sputum culture (79.1% vs. 11.4%, P = 0.001). A total of 48 samples from patients with confirmed TB were analyzed by both mNGS and X-pert MTB/RIF, and the sensitivity of mNGS for the diagnosis of active TB was significantly lower than that of X-pert MTB/RIF (64.6% vs. 85.4%, P = 0.031). Of the 106 pathogen-negative cases, 48 were ultimately considered non-infectious diseases, with a negative predictive value of 45.3%. Of the 381 pathogen-positive cases, 311 were eventually diagnosed as CAP, with a positive predictive value of 81.6%. A total of 487 patients were included in the evaluation of the therapeutic effect, and 67.1% improved with initial empirical antibiotic treatment. Of the 163 patients in which bacteria were detected, 77.9% improved with antibacterial therapy; of the 85 patients in which fungi were detected, 12.9% achieved remission after antifungal therapy. CONCLUSIONS: Overall, mNGS had unique advantages in the detection of suspected CAP pathogens. However, mNGS was not superior to X-pert MTB/RIF for the diagnosis of TB. In addition, mNGS was not necessary as a routine test for all patients admitted with suspected CAP. Furthermore, when fungi are detected by mNGS, antifungal therapy should be cautious.

Global One Health index for zoonoses: A performance assessment in 160 countries and territories.

The One Health (OH) approach is used to control/prevent zoonotic events. However, there is a lack of tools for systematically assessing OH practices. Here, we applied the Global OH Index (GOHI) to evaluate the global OH performance for zoonoses (GOHI-Zoonoses). The fuzzy analytic hierarchy process algorithm and fuzzy comparison matrix were used to calculate the weights and scores of five key indicators, 16 subindicators, and 31 datasets for 160 countries and territories worldwide. The distribution of GOHI-Zoonoses scores varies significantly across countries and regions, reflecting the strengths and weaknesses in controlling or responding to zoonotic threats. Correlation analyses revealed that the GOHI-Zoonoses score was associated with economic, sociodemographic, environmental, climatic, and zoological factors. Additionally, the Human Development Index had a positive effect on the score. This study provides an evidence-based reference and guidance for global, regional, and country-level efforts to optimize the health of people, animals, and the environment.

FibroScan-aspartate transaminase: A superior non-invasive model for diagnosing high-risk metabolic dysfunction-associated steatohepatitis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) with hepatic histological NAFLD activity score ≥ 4 and fibrosis stage F ≥ 2 is regarded as "at risk" non-alcoholic steatohepatitis (NASH). Based on an international consensus, NAFLD and NASH were renamed as metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), respectively; hence, we introduced the term "high-risk MASH". Diagnostic values of seven non-invasive models, including FibroScan-aspartate transaminase (FAST), fibrosis-4 (FIB-4), aspartate transaminase to platelet ratio index (APRI), etc. for high-risk MASH have rarely been studied and compared in MASLD. AIM: To assess the clinical value of seven non-invasive models as alternatives to liver biopsy for diagnosing high-risk MASH. METHODS: A retrospective analysis was conducted on 309 patients diagnosed with NAFLD via liver biopsy at Beijing Ditan Hospital, between January 2012 and December 2020. After screening for MASLD and the exclusion criteria, 279 patients were included and categorized into high-risk and non-high-risk MASH groups. Utilizing threshold values of each model, sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV), were calculated. Receiver operating characteristic curves were constructed to evaluate their diagnostic efficacy based on the area under the curve (AUROC). RESULTS: MASLD diagnostic criteria were met by 99.4% patients with NAFLD. The MASLD population was analyzed in two cohorts: Overall population (279 patients) and the subgroup (117 patients) who underwent liver transient elastography (FibroScan). In the overall population, FIB-4 showed better diagnostic efficacy and higher PPV, with sensitivity, specificity, PPV, NPV, and AUROC of 26.9%, 95.2%, 73.5%, 72.2%, and 0.75. APRI, Forns index, and aspartate transaminase to alanine transaminase ratio (ARR) showed moderate diagnostic efficacy, whereas S index and gamma-glutamyl transpeptidase to platelet ratio (GPR) were relatively weaker. In the subgroup, FAST had the highest diagnostic efficacy, its sensitivity, specificity, PPV, NPV, and AUROC were 44.2%, 92.3%, 82.1%, 67.4%, and 0.82. The FIB-4 AUROC was 0.76. S index and GPR exhibited almost no diagnostic value for high-risk MASH. CONCLUSION: FAST and FIB-4 could replace liver biopsy as more effectively diagnostic methods for high-risk MASH compared to APRI, Forns index, ARR, S index, and GPR; FAST is superior to FIB-4.

Complete biosynthesis of QS-21 in engineered yeast.

QS-21 is a potent vaccine adjuvant and remains the only saponin-based adjuvant that has been clinically approved for use in humans1,2. However, owing to the complex structure of QS-21, its availability is limited. Today, the supply depends on laborious extraction from the Chilean soapbark tree or on low-yielding total chemical synthesis3,4. Here we demonstrate the complete biosynthesis of QS-21 and its precursors, as well as structural derivatives, in engineered yeast strains. The successful biosynthesis in yeast requires fine-tuning of the host's native pathway fluxes, as well as the functional and balanced expression of 38 heterologous enzymes. The required biosynthetic pathway spans seven enzyme families-a terpene synthase, P450s, nucleotide sugar synthases, glycosyltransferases, a coenzyme A ligase, acyl transferases and polyketide synthases-from six organisms, and mimics in yeast the subcellular compartmentalization of plants from the endoplasmic reticulum membrane to the cytosol. Finally, by taking advantage of the promiscuity of certain pathway enzymes, we produced structural analogues of QS-21 using this biosynthetic platform. This microbial production scheme will allow for the future establishment of a structure-activity relationship, and will thus enable the rational design of potent vaccine adjuvants.

A nomogram based on contrast-enhanced ultrasound for evaluating the glomerulosclerosis rate in transplanted kidneys.

Background: A high rate of glomerulosclerosis serves as an important signal of poor response to treatment and a high risk of disease progression or adverse prognosis in transplanted kidneys. We hypothesized that contrast-enhanced ultrasound (CEUS) could serve as a novel imaging biomarker in the early prediction of glomerulosclerosis rate by evaluating renal allograft microcirculation. Methods: A retrospective analysis was performed on 143 transplanted kidney recipients with confirmed pathology, including 100 in the training group and 43 in the validation group. All patients underwent conventional ultrasound (CUS) and CEUS examinations. The patients were divided into two groups: those with >50% glomerulosclerosis and those with ≤50% glomerulosclerosis. The nomograms derived from independent predictors identified by multivariate logistic analysis were assessed using receiver operating characteristic (ROC) curve analysis, 1,000 bootstrap resamples, calibration curves, and decision curve analysis (DCA). Results: The patients with >50% glomerulosclerosis and those with ≤50% glomerulosclerosis showed statistically significant differences in CEUS parameters, including in peak intensity (PI) (25 vs. 30; P<0.001), absolute time to peak (ATTP) (10 vs. 9; P=0.004), and time to peak (TTP) (22 vs. 19.5; P=0.026). Multivariate analysis revealed that PI [odds ratio (OR) =0.852; 95% confidence interval (CI): 0.737-0.986], peak systolic velocity (PSV) of the interlobar artery (OR =0.850; 95% CI: 0.758-0.954), cortical echogenicity (OR =38.429; 95% CI: 3.695-399.641), and time since transplantation (OR =1.017; 95% CI: 1.006-1.028) were independent predictors of whether the glomerulosclerosis rate was >50% and were incorporated into the construction of a nomogram. The area under the curve (AUC) of the nomogram in the training and validation groups was 0.914 (95% CI: 0.840-0.960) and 0.909 (95% CI: 0.781-0.975), respectively, with a bootstrap resampling AUC of 0.877. The calibration curve and DCA confirmed the diagnostic performance of the nomogram model. Conclusions: The nomogram, which combined CUS, CEUS, and clinical indicators, exhibited notable predictive efficacy for the glomerulosclerosis rate in transplanted kidneys, thereby demonstrating the potential to improve clinical decision-making.

Using Mendelian randomization provides genetic insights into potential targets for sepsis treatment.

Sepsis is recognized as a major contributor to the global disease burden, but there is a lack of specific and effective therapeutic agents. Utilizing Mendelian randomization (MR) methods alongside evidence of causal genetics presents a chance to discover novel targets for therapeutic intervention. MR approach was employed to investigate potential drug targets for sepsis. Pooled statistics from IEU-B-4980 comprising 11,643 cases and 474,841 controls were initially utilized, and the findings were subsequently replicated in the IEU-B-69 (10,154 cases and 454,764 controls). Causal associations were then validated through colocalization. Furthermore, a range of sensitivity analyses, including MR-Egger intercept tests and Cochran's Q tests, were conducted to evaluate the outcomes of the MR analyses. Three drug targets (PSMA4, IFNAR2, and LY9) exhibited noteworthy MR outcomes in two separate datasets. Notably, PSMA4 demonstrated not only an elevated susceptibility to sepsis (OR 1.32, 95% CI 1.20-1.45, p = 1.66E-08) but also exhibited a robust colocalization with sepsis (PPH4 = 0.74). According to the present MR analysis, PSMA4 emerges as a highly encouraging pharmaceutical target for addressing sepsis. Suppression of PSMA4 could potentially decrease the likelihood of sepsis.

Long-Term Efficacy and Safety of High-Frequency Spinal Stimulation for Chronic Pain: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: The aim of our meta-analysis was to systematically assess the enduring effectiveness and safety of high-frequency spinal stimulation (HF-SCS) in the management of chronic pain. METHODS: We developed a comprehensive literature search strategy to identify clinical trials investigating the efficacy of high-frequency spinal stimulation for chronic pain. The search was conducted in multiple databases, including Web of Science, Cochrane, PubMed, and Embase, covering the period from 2004 to 2023. The inclusion and exclusion criteria established for this study were applied to screen the eligible literature by carefully reviewing abstracts and, when necessary, examining the full text of selected articles. To assess the quality of the included studies, we utilized the Risk of Bias assessment tool provided by the Cochrane Collaboration. The PRISMA method was followed for the selection of articles, and the quality of the articles was evaluated using the risk assessment table for bias provided by the Cochrane Collaboration. Meta-analysis of the selected studies was performed using Review Manager 5.4 and STATA 16.0. Effect sizes for continuous data were reported as mean differences (MD) or standardized mean differences (SMD), while categorical data were analyzed using relative risks (RR). RESULTS: According to our predefined literature screening criteria, a total of seven English-language randomized controlled trials (RCTs) were included in the meta-analysis. The findings from the meta-analysis demonstrated that HF-SCS exhibited superior efficacy in the long-term treatment of chronic pain when compared with the control group (RR=2.44, 95% CI: 1.20-4.96, P =0.01). Furthermore, HF-SCS demonstrated a statistically significant improvement in the Oswestry Disability Index score (mean difference MD=3.77, 95% CI: 1.17-6.38, P =0.005). However, for pain assessment (standardized mean difference SMD=-0.59, 95% CI: -1.28 to 0.10, P =0.09), Patient Global Impression of Improvement (PGI-I) score (MD=0.11, 95% CI: -0.66 to 0.88, P =0.78 for 6 months; MD=0.02, 95% CI: -0.42 to 0.43, P =0.97 for 12 mo), Clinical Global Impression of Improvement (CGI-I) score (MD=-0.58, 95% CI: -1.62 to 0.43, P =0.27 for 6 mo; MD=-0.23, 95% CI: -0.94 to 0.48, P =0.52 for 12 mo), and occurrence of adverse effects (odds ratio [OR]=0.77, 95% CI: 0.23-2.59, P =0.67), HF-SCS did not show statistically sufficient effects compared with the control group. CONCLUSIONS: The findings from our comprehensive review and meta-analysis offer encouraging data about the prolonged efficacy and safety of HF-SCS in chronic pain management on some but not all outcomes. Recognizing the constraints of the existing evidence is crucial. Additional clinical trials, meticulously planned and stringent, are essential to bolster the current body of evidence and reach more conclusive findings.

A one-two punch strategy for diabetic wound management based on an antibiotic-hybrid biomineralized iron sulfide nanoparticle.

Bacterial infection and immune imbalance are the primary culprits behind chronic wounds in individuals with diabetes, impeding the progression of damaged tissues towards normal healing. To achieve a harmonious balance between pro- and anti-inflammation within these infected areas, herein, we propose a one-two punch strategy for on-demand therapy of diabetes-infected wounds, utilizing an azithromycin (AZM)-hybrid nanocomposite termed GOx@FexSy/AZM. During the infective stage, the nanocomposite facilitates the production of ROS, coupled with the burst release of AZM and H2S gas, effectively dismantling biofilms and achieving rapid sterilization. Subsequently, the hyperinflammatory response induced by antibiosis is significantly mitigated through the synergistic action of tissue H2S and the prolonged half-life of AZM. These components inhibit the activity of pro-inflammatory transcription factors (AP-1 and NF-κB) within macrophages, thereby promoting the polarization of macrophages towards a reparative M2 phenotype and facilitating tissue remodeling. By catering to the diverse requirements of wound healing at different stages, this nanocomposite accelerates a sensible transition from inflammation to the reparative phase. In summary, this one-two punch strategy gives an instructive instance for procedural treatment of diabetes wound infection. STATEMENT OF SIGNIFICANCE: The treatment of diabetic wound infection presents two major challenges: the diminished antibacterial efficacy arising from biofilm formation and bacterial resistance, as well as the inadequate transition of the wound microenvironment from pro-inflammatory to anti-inflammatory states after bacterial clearance. In this work, a biomineralized iron sulfide nanocomposite was prepared to mediate cascade catalytic (ROS storm) / antibiotic (AZM) / gas (H2S) triple-synergetic antibacterial therapy during the initial stage of bacterial infection, achieving the goal of rapid bactericidal effect; Subsequently, the residual H2S and long half-life AZM would inhibit the key pro-inflammatory transcription factors and promote the macrophages polarization to reparative M2, which effectively mediated tissue repair after hyperinflammatory reactions, leading to orderly treatment of hyperglycemic infected wounds.

[A multicenter clinical study on the treatment of lateral epicondylitis of humerus by manipulation].

OBJECTIVE: To investigate clinical effect of tendons pulling,poking and kneading for the treatment of external humeral epicondylitis. METHODS: From January 2018 to December 2021,a multicenter randomized controlled study was performed to collect 192 patients with external humeral epicondylitis in Wangjing Hospital,Beijing Dianli Hospital,and Beijing Fengsheng Osteotraumatology Hospital,respectively,and they were divided into treatment group and control group by random number table method. There were 96 patients in treatment group,including 36 males and 60 females,aged from 28 to 60 years old with an average of (41.20±5.50) years old;the course of disease ranged from 1 to 14 days with an average of (5.24±1.35) days;they were treated once every other day for 2 weeks. There were 96 patients in control group ,including 33 males and 63 females,aged from 26 to 60 years old with an average of (43.35±7.75) years old;the course of disease ranged from 1 to 14 days with an average of (5.86±1.48) days;they were treated with topical voltaalin combined with elbow joint fixation for 2 weeks. Visual analogue scale (VAS) and Hospital for Surgery Scoring System (HSS) elbow pronation and supination angles,wrist metacarpal flexion and dorsal extension angles,elbow tenderness between two groups were compared before treatment and at 1,3,5,7,11 and 13 days after treatment;Hospital for Surgery Scoring System 2 (HSS2) was compared before treatment and the final treatment. RESULTS: All patients were followed up for 10 to 14 days with an average of (12±1.6) days. VAS between treatment group and control group before treatment were 6.83±1.36 and 6.79±1.58,respectively,and decreased to 1.49±1.09 and 2.11±1.81 after the final treatment. VAS of treatment group were significantly lower than those of control group at 1,3,5,7,9,11 and 13 days after treatment (P<0.05). HSS between two groups were 61.73±11.00 and 36.47±12.45 before treatment,respectively,and increased to 94.42±5.9 and 91.44±9.11 at the final treatment. HSS of treatment group were significantly higher than those of control group at 1,3,5,7,9,11 and 13 days after treatment (P<0.05). On the 5th day after treatment,the external and internal rotation angles of elbow in treatment group were (66.41±12.69) ° and (66.35±13.54) °,while those in control group were (62.08±16.03) ° and (61.77±16.35) °. On the 7th day after treatment,the external and internal rotation angles of elbow were (69.79±12.64) ° and (70.02±13.55) ° in treatment group,and (65.28±15.86) ° and (65.09±16.67) ° in control group. Elbow joint motion in treatment group was higher than that in control group (P<0.05). On the 5th day after treatment,angles of wrist dorsiflexion and palm flexion were (39.43±15.94) ° and (46.68±11.10) ° in treatment group,and (38.51±18.49) ° and (44.27±13.58) ° in control group. On the 7th day after treatment,angles of wrist dorsiflexion and palm flexion were (42.52±16.50) ° and (49.23±10.96) ° in treatment group,and (41.18±20.09) ° and (46.64±14.63) ° in control group. The motion of wrist joint in treatment group was higher than that in control group (P<0.05). On the 13th day after treatment,HSS2 in treatment group 93.61±6.32 were higher than those in control group 92.06±7.94(P<0.05). There was no significant difference in elbow tenderness between two groups at each time point (P>0.05). CONCLUSION: Voltaren external treatment combined with elbow fixation and tendons pulling,poking and kneading could effectively improve symptoms of external humeral epicondylitis. Compared with voltaren external treatment,tendons pulling,poking and kneading has advantages of longer analgesic time and better elbow function recovery.