The occurrence of banana Fusarium wilt aggravates antibiotic resistance genes dissemination in soil.

The spread of antibiotic resistance genes (ARGs) and subsequent soil-borne disease outbreaks are major threats to soil health and sustainable crop production. However, the relationship between occurrences of soil-borne diseases and the transmission of soil ARGs remains unclear. Here, soil ARGs, mobile genetic elements and microbial communities from co-located disease suppressive and conducive banana orchards were deciphered using metagenomics and metatranscriptomics approaches. In total, 23 ARG types, with 399 subtypes, were detected using a metagenomics approach, whereas 23 ARG types, with 452 subtypes, were discovered using a metatranscriptomics method. Furthermore, the metagenomics analysis revealed that the ARG total abundance levels were greater in rhizospheres (0.45 ARGs/16S rRNA on average) compared with bulk (0.32 ARGs/16S rRNA on average) soils. Interestingly, metatranscriptomics revealed that the total ARG abundances were greater in disease-conducive (8.85 ARGs/16S rRNA on average) soils than disease suppressive (1.45 ARGs/16S rRNA on average) soils. Mobile genetic elements showed the same trends as ARGs. Network and binning analyses indicated that Mycobacterium, Streptomyces, and Blastomonas are the main potential hosts of ARGs. Furthermore, Bacillus was significantly and negatively correlated with Fusarium (P < 0.05, r = -0.84) and hosts of ARGs (i.e., Mycobacterium, Streptomyces, and Blastomonas). By comparing metagenomic and metatranscriptomic analyses，this study demonstrated that metatranscriptomics may be more sensitive in indicating ARGs activities in soil. Our findings enable the more accurate assessment of the transmission risk of ARGs. The data provide a new perspective for recognizing soil health, in which soil-borne disease outbreaks appear to be associated with ARG spread, whereas beneficial microbe enrichment may mitigate wilt disease and ARG transmission.

Delivery of SiRNA-PD-L1 by attenuated Salmonella in combination with oxaliplatin in a hepatocellular carcinoma mouse model.

Oxaliplatin is currently used for chemotherapy in patients with hepatocellular carcinoma, but its increasing tolerance to tumours over time limits its clinical application. Studies have shown that high PD-L1 expression promotes the polarization of M2 macrophages. The increased infiltration of M2 macrophages, including those in HCC, is positively correlated with poor prognosis in various solid tumours. We found that oxaliplatin promoted the expression of PD-L1 in liver cancer cells, which might be attributed partly to the tolerance of tumours to oxaliplatin. Therefore, in this study, we explored the antitumour effect of attenuated Salmonella carrying siRNA-PD-L1 combined with oxaliplatin via Western blotting, immunohistochemistry, immunofluorescence, and flow cytometry. The results revealed that attenuated Salmonella carrying siRNA-PD-L1 combined with oxaliplatin more significantly inhibited tumour growth in tumour-bearing mice, suppressed the expression of PD-L1 in tumour tissue, increased the apoptosis of tumour cells and the expression of the tumour-related protein cleaved-caspase3, and increased the infiltration of M1 macrophages and T lymphocytes in tumour tissues. Moreover, the combination therapy increased the activation of T cells and the number of T lymphocytes and NK cells in the spleens of the mice and improved the overall antitumour immune response in the mice. Our results confirmed that attenuated Salmonella harbouring siRNA-PD-L1 combined with oxaliplatin had a significant antitumour effect and did not increase the incidence of toxic side effects, providing a theoretical reference for addressing oxaliplatin tolerance in the treatment of hepatocellular carcinoma.

Association between metabolic score for insulin resistance and regression to normoglycemia from prediabetes in Chinese adults: A retrospective cohort study.

BACKGROUND: Metabolic score for insulin resistance (METS-IR) is a surrogate index to estimate insulin sensitivity. The aim of this study was to examine the association between METS-IR and regression to normoglycemia in Chinese adults with prediabetes. METHODS: A total of 15,415 Chinese adults with prediabetes defined by their fasting blood glucose were included in this retrospective study. The association between METS-IR and regression to normoglycemia from prediabetes was evaluated using the Cox proportional hazards regression model. A Cox proportional hazards regression with cubic spline function was performed to explore the nonlinear association between METS-IR and regression to normoglycemia. Kaplan-Meier curves was used to describe the probability of regression to normoglycemia from prediabetes. RESULTS: In multivariate Cox proportional hazards regression analyses, the increase in METS-IR was independently associated with a reduced probability of regression to normoglycemia from prediabetes (all p < 0.01 in models 1-3). A nonlinear association between METS-IR and the probability of regression to normoglycemia was observed, with an inflection point of 49.3. The hazard ratio on the left side of the inflection point was 0.965 (95% CI 0.953-0.976). Subgroup analyses demonstrated the robustness of our findings. CONCLUSION: This study demonstrated a negative and nonlinear association between METS-IR and regression to normoglycemia in Chinese adults with prediabetes. When METS-IR is below 49.3, reducing METS-IR could significantly increase the probability of regression to normoglycemia from prediabetes.

Ultrabroadband nonlinear enhancement of mid-infrared frequency upconversion in hyperbolic metamaterials.

Metamaterials have demonstrated significant potential for enhancing nonlinear processes at the nanoscale. The presence of narrowband hot-spots and highly inhomogeneous mode-field distributions often limit the enhancement of nonlinear interactions over larger spatial scales. This has posed a formidable challenge in achieving simultaneous enhancement across a broadband spectral range, significantly constraining the potential of photonic nanostructures in enhancing nonlinear frequency conversion. Here, we propose a broadband resonant mode matching method through near-field examinations that supports the multipole modes and enables the development of an ultrabroadband-enhanced 3-5 µm mid-infrared frequency upconversion technique utilizing a hyperbolic triangular pyramidal metasurface. The gap-plasma mode of the hyperbolic metamaterial multilayer system excites narrowly high-order resonances at near-infrared pump light wavelengths, while the slow-light effect generated by the dipoles achieves ultrabroadband near-field enhancement at mid-infrared wavelengths. The symmetry breaking of the triangular structure localizes these resonant modes at the tips, enabling mode-matched modulation at different wavelengths, and thus boosting the nonlinear frequency conversion process. Our approach provides a promising platform for metasurface-based frequency conversion techniques.

Development of a 2A peptide-based multigene expression system and its application for enhanced production of ganoderic acids in Ganoderma lucidum.

Ganoderma has received much attention for its medicinal value, but the manipulation of multiple genes remains a challenge, hindering the genetic engineering of this species for the development of cell factories. Here, we first showed that the presence of an intron is necessary for the efficient expression of the endogenous cDNA of carboxin-resistant gene (cbx) in G. lucidum. Then, the self-cleaving function of 2 A peptide was investigated in G. lucidum by linking cbx cDNA to the codon-optimized hygromycin B-resistant gene (ophph) using the 2A-peptide sequence. The results showed that cbx cDNA and ophph can be successfully expressed in G. lucidum in a bicistronic manner from a single transcript. Moreover, the expression of both genes was not affected by the order within the 2 A cassette. In addition, simultaneous expression of cbx cDNA, ophph, and codon-optimized yellow fluorescent protein gene (opyfp) was conducted for the first time in G. lucidum using the 2 A peptide-based approach. The developed method was successfully applied to express both cDNA of the 3-hydroxy-3-methylglutaryl coenzyme A reductase (hmgr) and squalene epoxidase gene (se) for enhanced production of ganoderic acids (GAs) in G. lucidum. The engineered strain produced the maximum content of GA-Mk, GA-T, GA-S, and GA-Me were 26.56±3.53,39.58±3.75, 16.54±2.16, and 19.1±1.87 µg/100 mg dry weight, respectively. These values were 3.85-, 4.74-, 3.65-, and 3.23-fold higher than those produced by the control strain. The developed method will be useful for the manipulation of complex metabolic or regulatory pathways involving multiple genes in Ganoderma.

Angiogenesis unveiled: Insights into its role and mechanisms in cartilage injury.

Osteoarthritis (OA) commonly results in compromised mobility and disability, thereby imposing a significant burden on healthcare systems. Cartilage injury is a prevalent pathological manifestation in OA and constitutes a central focus for the development of treatment strategies. Despite the considerable number of studies aimed at delaying this degenerative process, their outcomes remain unvalidated in preclinical settings. Recently, therapeutic strategies focused on angiogenesis have attracted the growing interest from researchers. Thus, we conducted a comprehensive literature review to elucidate the current progress in research and pinpoint research gaps in this domain. Additionally, it provides theoretical guidance for future research endeavors and the development of treatment strategies.

Integrated process of Tetrasphaera-dominated in-situ waste activated sludge fermentation, biological phosphorus removal and endogenous denitrification in single reactor for treatment of wastewater with limited carbon sources.

An integrated process of sludge in-situ fermentation, biological phosphorus removal and endogenous denitrification (ISFPR-ED) was developed to treat low ratio of chemical oxygen demand to nitrogen (COD/N) wastewater and waste activated sludge (WAS) in a single reactor. Nutrient removal and WAS reduction were achieved due to Tetrasphaera-dominated sludge fermentation provided organic carbon in extending the anaerobic duration. The WAS reduction efficiency, effluent orthophosphate (PO43--P) and total inorganic nitrogen reached 28.1 %, less than 0.4 and 7.2 mg/L, respectively. While organic carbon was reduced by 67 %. Tetrasphaera, conventional polyphosphate accumulating organisms (PAOs) stored glycogen, amino acids, and PHA for nutrient removal. Excess energy from fermentation enhanced anaerobic PO43--P uptake by Tetrasphaera. Tetrasphaera was the dominant PO43--P removal and fermentation bacteria, working synergistically with conventional PAOs and fermenting microorganisms. This integrated process improves nutrient removal efficiency and reduces operating costs for carbon addition and WAS disposal in wastewater treatment.

Response Enhancement in High-Temperature H2S-Treated Metal Oxide Gas Sensors.

Metal oxide gas sensors (MOGS), crucial components in monitoring air quality and detecting hazardous gases, are well known for their poisoning effects when exposed to certain gas molecules, such as hydrogen sulfide. Surprisingly, our research reveals that high-temperature H2S treatment leads to an enhancement effect rather than response decay. This study investigates the time-decaying response enhancement, being attributed to the formation of metal sulfide and metal sulfate on the metal oxide's surface, enhancing the electronic sensitization. Such an enhancement effect is demonstrated for various gases, including CO, CH3CH2OH, CH4, HCHO, and NH3. Additionally, the impacts of H2S treatment on the response and recovery time are also observed. Surface compositional analysis are conducted with X-ray photoelectron spectroscopy. A proposed mechanism for the enhancement effect is elaborated, highlighting the role of electronic sensitization and the sulfide-sulfate component. This research offers valuable insights into the potential applications of metal oxide sensors in sulfide-presented harsh environments in gas sensing, encouraging future exploration of optimized sensor materials, operation temperature, and the development of hydrogen sulfide poisoning-resistant and higher sensitivity MOGS.

Quantitative trait locus analysis of gray leaf spot resistance in the maize IBM Syn10 DH population.

KEY MESSAGE: The exploration and dissection of a set of QTLs and candidate genes for gray leaf spot disease resistance using two fully assembled parental genomes may help expedite maize resistance breeding. The fungal disease of maize known as gray leaf spot (GLS), caused by Cercospora zeae-maydis and Cercospora zeina, is a significant concern in China, Southern Africa, and the USA. Resistance to GLS is governed by multiple genes with an additive effect and is influenced by both genotype and environment. The most effective way to reduce the cost of production is to develop resistant hybrids. In this study, we utilized the IBM Syn 10 Doubled Haploid (IBM Syn10 DH) population to identify quantitative trait loci (QTLs) associated with resistance to gray leaf spot (GLS) in multiple locations. Analysis of seven distinct environments revealed a total of 58 QTLs, 49 of which formed 12 discrete clusters distributed across chromosomes 1, 2, 3, 4, 8 and 10. By comparing these findings with published research, we identified colocalized QTLs or GWAS loci within eleven clustering intervals. By integrating transcriptome data with genomic structural variations between parental individuals, we identified a total of 110 genes that exhibit both robust disparities in gene expression and structural alterations. Further analysis revealed 19 potential candidate genes encoding conserved resistance gene domains, including putative leucine-rich repeat receptors, NLP transcription factors, fucosyltransferases, and putative xyloglucan galactosyltransferases. Our results provide a valuable resource and linked loci for GLS marker resistance selection breeding in maize.

Bi-parental graph strategy to represent and analyze hybrid plant genomes.

Hybrid plants are found extensively in the wild, and they often demonstrate superior performance of complex traits over their parents and other selfing plants. This phenomenon, known as heterosis, has been extensively applied in plant breeding for decades. However, the process of decoding hybrid plant genomes has seriously lagged due to the challenges associated with genome assembly and the lack of appropriate methodologies for their subsequent representation and analysis. Here, we present the assembly and analysis of two hybrids, an intraspecific hybrid between two maize (Zea may ssp. mays) inbred lines and an interspecific hybrid between maize and its wild relative teosinte (Zea may ssp. parviglumis), utilizing a combination of PacBio High Fidelity (HiFi) sequencing and chromatin conformation capture sequencing data. The haplotypic assemblies are well-phased at chromosomal scale, successfully resolving the complex loci with extensive parental structural variations (SVs). By integrating into a bi-parental genome graph, the haplotypic assemblies can facilitate downstream short-reads-based SV calling and allele-specific gene expression analysis, demonstrating outstanding advantages over a single linear genome. Our work offers a comprehensive workflow that aims to facilitate the decoding of numerous hybrid plant genomes, particularly those with unknown or inaccessible parentage, thereby enhancing our understanding of genome evolution and heterosis.

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.

Thioredoxin-1 Protects Neurons Through Inhibiting NLRP1-Mediated Neuronal Pyroptosis in Models of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease all over the world. In the last decade, accumulating proofs have evidenced that neuroinflammation is intimately implicated in the pathogenesis of AD and activation of NOD-like receptor family pyrin domain-containing 1 (NLRP1) inflammasome can induce neuronal pyroptosis and in turn lead to neuronal loss in AD. Thioredoxin-1 (Trx-1), a multifunctional molecule with anti-inflammation in human tissues, displays crucial neuroprotective roles in AD. Our previous research preliminarily found that Trx-1 inhibition enhanced the expression of NLRP1, caspase-1, and gasdermin D (GSDMD) in Aß25-35-treated PC12 cells. However, it is largely unknown if Trx-1 can inhibit NLRP1-mediated neuronal pyroptosis in AD neurons. In this study, it was verified that the protein levels of NLRP1, caspase-1, and GSDMD were significantly increased in Aß25-35-treated mouse HT22 and primary hippocampal neurons. Suppression of Trx-1 with PX-12, a selective inhibitor of Trx-1, or Trx-1 knockdown further activated NLRP1-mediated neuronal pyroptosis. On the contrary, lentivirus infection-mediated Trx-1 overexpression in differentiated PC12 cells dramatically reversed expression of NLRP1, caspase-1, and GSDMD. Furthermore, Trx-1 overexpression mediated by adeno-associated virus in the hippocampal tissues of APP/PS1 mice likewise attenuated the activation of NLRP1-mediated neuronal pyroptosis, as well as reduced the hippocampal deposition of Aß and ameliorated the cognitive function of APP/PS1 mice. In conclusion, this article predicates a novel molecular mechanism by which Trx-1 exploits neuroprotection through attenuating NLRP1-mediated neuronal pyroptosis in AD models, suggesting that Trx-1 may be a promising therapeutic target for AD.

Determination of cotinine and 3-hydroxynicotinine in human serum by liquid chromatography-tandem mass spectrometry and its application.

In this study, we developed a method for determining cotinine and 3-hydroxycotinine in human serum and established a methodology for an in-depth study of tobacco exposure and health. After the proteins in the human serum samples were precipitated with acetonitrile, they were separated on a ZORBAX SB-Phenyl column with a mobile phase of methanol encompassing 0.3% formic acid-water encompassing 0.15% formic acid. The measurement was performed on an API5500 triple quadrupole mass spectrometer in the multiple reaction monitoring mode. Cotinine, 3-hydroxycotinine, and cotinine-d3 isotope internal standards were held for 2.56 minutes, 1.58 minutes, and 2.56 minutes, respectively. In serum, the linear range was 0.05 to 500 ng·mL-1 for cotinine and 0.50 to 1250 ng·mL-1 for 3-hydroxycotinine. The lower limit of quantification (LLOQ) was 0.05 ng·mL-1 and 0.5 ng·mL-1 for cotinine and 3-hydroxycotinine, respectively. The intra-day and inter-day relative standard deviations were <11%, and the relative errors were within ±â€…7%. Moreover, the mean extraction recoveries of cotinine and 3-hydroxycotinine were 98.54% and 100.24%, respectively. This method is suitable for the rapid determination of cotinine and 3-hydroxycotinine in human serum because of its rapidity, sensitivity, strong specificity, and high reproducibility. The detection of cotinine levels in human serum allows for the identification of the cutoff value, providing a basis for differentiation between smoking and nonsmoking populations.

Antibiotic prophylaxis for surgical wound infections in clean and clean-contaminated surgery: an updated systematic review and meta-analysis.

BACKGROUND: The efficacy and necessity of prophylactic antibiotics in clean and clean-contaminated surgery remains controversial. METHODS: The studies were screened and extracted using databases including PubMed, Embase, Cochrane Library, Web of Science, and Clinical Trials.gov according to predefined eligibility criteria. Randomized controlled trials (RCTs) comparing the effect of preoperative and postoperative prophylactic antibiotic use on the incidence of surgical site infections (SSIs) in patients undergoing any clean or clean-contaminated surgery. RESULTS: A total of 16 189 participants in 48 RCTs were included in the primary meta-analysis following the eligibility criteria. The pooled odds ratio (OR) for SSI with antibiotic prophylaxis versus placebo was 0.60 (95% CI: 0.53-0.68). The pooled OR among gastrointestinal, oncology, orthopedics, neurosurgery, oral, and urology surgery was 3.06 (95% CI: 1.05-8.91), 1.16 (95% CI: 0.89-1.50), 2.04 (95% CI: 1.09-3.81), 3.05 (95% CI: 1.25-7.47), 3.55 (95% CI: 1.78-7.06), and 2.26 (95% CI: 1.12-4.55), respectively. Furthermore, the summary mean difference (MD) for patients' length of hospitalization was -0.91 (95% CI: -1.61, -0.16). The results of sensitivity analyses for all combined effect sizes showed good stability. CONCLUSION: Antibiotics are both effective, safe, and necessary in preventing surgical wound infections in clean and clean-contaminated procedures, attributed to their reduction in the incidence of surgical site infections as well as the length of patient hospitalization.

Minimal Kinetic Model of Direct Air Capture of CO2 by Supported Amine Sorbents in Dry and Humid Conditions.

Dilute concentration (∼400 ppm) and humidity are two important factors in the direct air capture (DAC) of CO2 by supported sorbents. In this work, a minimal DAC CO2 adsorption-kinetics model was formulated for supported amine sorbents under dry and humid conditions. Our model fits well with a recent DAC experiment with supported amine sorbent in both dry and humid conditions. Temperature and flow rate effects on breakthrough curves were quantitatively captured, and increasing temperature led to faster CO2 adsorption kinetics. Moisture was shown to broaden the breakthrough curve with slower CO2 adsorption kinetics but significantly improve the uptake capacity. The present minimal model provides a versatile platform for kinetic modeling of the DAC of CO2 on supported amine and other chemisorption systems.

Development of a novel humanized anti-TSLP monoclonal antibody HZ-1127 with anti-allergic diseases and cancer potential.

Thymic stromal lymphopoietin (TSLP) is a member of the IL-2 cytokine family and has been widely recognized as a master regulator of type 2 inflammatory responses at barrier surfaces. Recent studies found dysregulation of the TSLP-TSLP receptor (TSLPR) pathway is associated with the pathogenesis of not only allergic diseases but also a wide variety of cancers including both solid tumors and hematological tumors. Thus, the blockade of TSLP represents an attractive therapeutic strategy for allergic diseases and cancer. In this study, we report the development of a novel humanized anti-TSLP monoclonal antibody (mAb) HZ-1127. Binding affinity, specificity, and ability of HZ-1127 in inhibiting TSLP were tested. HZ-1127 selectively binds to the TSLP cytokine with high affinity and specificity. Furthermore, HZ-1127 dramatically inhibits TSLP-dependent STAT5 activation and is more potent than Tezepelumab, which is an FDA-approved humanized mAb against TSLP for severe asthma treatment in inhibiting TSLP-induced CCL17 and CCL22 chemokines secretion in human peripheral blood mononuclear cells. Our pre-clinical study demonstrates that HZ-1127 may serve as a potential therapeutic agent for allergic diseases and cancer.

Highly stable localized surface plasmon resonance of Cu nanoparticles obtained via oxygen plasma irradiation.

Copper nanoparticles (CuNPs) possess strong localized surface plasmon resonance (LSPR) in visible light. However, CuNPs are not chemically stable in air, which has seriously hindered the applications based on the LSPR of CuNPs. We developed an artificial method to passivate CuNPs as Al naturally does in air, preventing the oxidation of CuNPs through swift oxidation of the surface atoms via oxygen plasma irradiation. A hemispheric core-shell structure of CuNPs uniformly covered by a dense CuO shell (CuNPs@d-CuO) was constructed. The 4 nm d-CuO shell can prevent CuNPs from further oxidation. As a result, the LSPR of the CuNPs is stable in air over 180 days.

Posterior perforator tibial artery flaps for soft tissue defects of limbs: a retrospective cohort study.

PURPOSE: To investigate the clinical effect of posterior perforator tibial artery flaps on repairing soft tissue defects of limbs. METHODS: From June 2012 to June 2021, 14 cases of soft tissue defects of limbs were repaired with pedicled or free flaps of posterior perforator tibial artery. Among them, there were 9 cases of pedicled flaps and 5 cases of free flaps. The donor sites were closed directly or covered with skin grafting. The defects area varied from 3 × 5 cm to 7 × 16 cm. All cases were followed up for 1 year to 2 years. RESULTS: All flaps survived completely except 3 cases with distal end necrosis and the 3 cases healed after dressing change. There were not any other complications at both donor and recipient sites. Appearance of the recipient sites was close to the surrounding skin. All patients were satisfied with the results. CONCLUSION: Posterior perforator tibial artery flaps have the advantages of relatively simple technique, few damage, few complications and satisfying appearance. It is a good choice for soft tissue defects of limbs.