Assessment of pathological grade and variants of bladder cancer with a continuous-time random-walk diffusion model.

Purpose: To evaluate the efficacy of high b-value diffusion-weighted imaging (DWI) with a continuous-time random-walk (CTRW) diffusion model in determining the pathological grade and variant histology (VH) of bladder cancer (BCa). Methods: A total of 81 patients (median age, 70 years; range, 35-92 years; 18 females; 66 high grades; 30 with VH) with pathologically confirmed bladder urothelial carcinoma were retrospectively enrolled and underwent bladder MRI on a 3.0T MRI scanner. Multi-b-value DWI was performed using 11 b-values. Three CTRW model parameters were obtained: an anomalous diffusion coefficient (D) and two parameters reflecting temporal (α) and spatial (ß) diffusion heterogeneity. The apparent diffusion coefficient (ADC) was calculated using b0 and b800. D, α, ß, and ADC were statistically compared between high- and low-grade BCa, and between pure urothelial cancer (pUC) and VH. Comparisons were made using the Mann-Whitney U test between different pathological states. Receiver operating characteristic curve analysis was used to assess performance in differentiating the pathological states of BCa. Results: ADC, D, and α were significantly lower in high-grade BCa compared to low-grade, and in VH compared to pUC (p < 0.001), while ß showed no significant differences (p > 0.05). The combination of D and α yielded the best performance for determining BCa grade and VH (area under the curves = 0.913, 0.811), significantly outperforming ADC (area under the curves = 0.823, 0.761). Conclusion: The CTRW model effectively discriminated pathological grades and variants in BCa, highlighting its potential as a noninvasive diagnostic tool.

Mechanistic insights on the preparation of 5-methyl-2-hexanone by hydrogenation of 5-methyl-3-hexen-2-one using Pd/Al2O3 catalysts.

5-methyl-2-hexanone is used as a versatile polymerization solvent for industrial preparation processes of bulk and fine chemicals. An efficient catalyst, Pd/γ-Al2O3, is reported for the preparation of 5-methyl-2-hexanone by selective hydrogenation of 5-methyl-3-hexen-2-one. The catalyst exhibits remarkable activity and selectivity even at atmospheric pressure and low temperature (1 atm, 80 °C). The influence weight of reaction conditions on the reaction process was obtained through the Artificial Neural Network model, which were reaction pressure, reaction temperature and liquid hourly space velocity in order. The reaction kinetics and mechanism of 5-methyl-2-hexanone preparation by hydrogenation over Pd/γ-Al2O3 catalyst were investigated. The hydrogenation reaction pathway of 5-methyl-3-hexen-2-one was obtained by using Density functional theory calculations, and the mechanism of selective hydrogenation of CC double bonds and CO double bonds was revealed. A kinetic model based on the LHHW model assumption was also proposed and compared with experimental results demonstrating good predictability.

Optimization of an adeno-associated viral vector for epidermal keratinocytes in vitro and in vivo.

BACKGROUND: Local gene therapies, including in vivo genome editing, are highly anticipated for the treatment of genetic diseases in skin, especially the epidermis. While the adeno-associated virus (AAV) is a potent vector for in vivo gene delivery, the lack of efficient gene delivery methods has limited its clinical applications. OBJECTIVE: To optimize the AAV gene delivery system with higher gene delivery efficiency and specificity for epidermis and keratinocytes (KCs), using AAV capsid and promoter engineering technologies. METHODS: AAV variants with mutations in residues reported to be critical to determine the tropism of AAV2 for KCs were generated by site-directed mutagenesis of AAVDJ. The infection efficiency and specificity for KCs of these variants were compared with those of previously reported AAVs considered to be suitable for gene delivery to KCs in vitro and in vivo. Additionally, we generated an epidermis-specific promoter using the most recent short-core promoter and compared its specificity with existing promoters. RESULTS: A novel AAVDJ variant capsid termed AAVDJK2 was superior to the existing AAVs in terms of gene transduction efficiency and specificity for epidermis and KCs in vitro and in vivo. A novel tissue-specific promoter, termed the K14 SCP3 promoter, was superior to the existing promoters in terms of gene transduction efficiency and specificity for KCs. CONCLUSION: The combination of the AAVDJK2 capsid and K14 SCP3 promoter improves gene delivery to epidermis in vivo and KCs in vitro. The novel AAV system may benefit experimental research and development of new epidermis-targeted gene therapies.

Impact of Aphasia on Brain Activation to Motor Commands in Patients with Acute Intracerebral Hemorrhage.

BACKGROUND: Brain activation to motor commands is seen in 15% of clinically unresponsive patients with acute brain injury. This state called cognitive motor dissociation (CMD) is detectable by electroencephalogram (EEG) or functional magnetic resonance imaging, predicts long-term recovery, and is recommended by recent guidelines to support prognostication. However, false negative CMD results are a particular concern, and occult aphasia in clinically unresponsive patients may be a major factor. This study aimed to quantify the impact of aphasia on CMD testing. METHODS: We prospectively studied 61 intensive care unit patients admitted with acute primary intracerebral hemorrhage (ICH) who had behavioral evidence of command following or were able to mimic motor commands. All patients underwent an EEG-based motor command paradigm used to detect CMD and comprehensive aphasia assessments. Logistic regression was used to identify predictors of brain activation, including aphasia types and associations with recovery of independence (Glasgow Outcome Scale-Extended score ≥ 4). RESULTS: Of 61 patients, 50 completed aphasia and the EEG-based motor command paradigm. A total of 72% (n = 36) were diagnosed with aphasia. Patients with impaired comprehension (i.e., receptive or global aphasia) were less likely to show brain activation than those with intact comprehension (odds ratio [OR] 0.23 [95% confidence interval 0.05-0.89], p = 0.04). Brain activation was independently associated with Glasgow Outcome Scale-Extended ≥ 4 by 12 months (OR 2.4 [95% confidence interval 1.2-5.0], p = 0.01) accounting for the Functional Outcome in Patients with Primary ICH score (OR1.3 [95% confidence interval 1.0-1.8], p = 0.01). CONCLUSIONS: Brain activation to motor commands is four times less likely for patients with primary ICH with impaired comprehension. False negative results due to occult receptive aphasia need to be considered when interpreting CMD testing. Early detection of brain activation may help predict long-term recovery in conscious patients with ICH.

A four-in-one first-in-human study to assess safety, tolerability, pharmacokinetics, pharmacodynamics, and concentration-QTc relationship of HRS-1780, a selective non-steroidal mineralocorticoid receptor antagonist, in healthy men.

BACKGROUND: This first-in-human study evaluated HRS-1780, an oral selective non-steroidal mineralocorticoid receptor antagonist, in healthy men. RESEARCH DESIGN AND METHODS: In single ascending dose (SAD) part, 10 participants for each dose cohort (5, 10, 20, 40, 60, and 80 mg) were randomized (8:2) to HRS-1780 or placebo. In multiple ascending dose part, 12 participants for each dose (10, 20, and 40 mg) were randomized (9:3) to HRS-1780 or placebo once daily for 7 days. The primary endpoint was safety and tolerability. RESULTS: HRS-1780 was well tolerated with all adverse events being mild. In the steady state, the median time to maximum concentration (Tmax) was 0.750 h and mean half-life was 1.76-1.96 h. High-fat/high-calorie meal prolonged Tmax but did not affect exposure. Multiple dosing of HRS-1780 at 40 mg showed a decreasing trend in systolic blood pressure compared with placebo. Changes in plasma aldosterone and norepinephrine with HRS-1780 were higher compared to placebo. Upper bounds of two-sided 90% confidence interval of placebo-adjusted change-from-baseline QTcF were below 10 msec at the maximum concentration in SAD. The trial had limited sample size and short study duration. CONCLUSIONS: HRS-1780 had favorable safety and pharmacokinetic profiles and did not cause clinically meaningful QTcF prolongation. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05638126).

Gasdermin-E-mediated pyroptosis drives immune checkpoint inhibitor-associated myocarditis via cGAS-STING activation.

Immune checkpoint inhibitor (ICI)-induced myocarditis involves intensive immune/inflammation activation; however, its molecular basis is unclear. Here, we show that gasdermin-E (GSDME), a gasdermin family member, drives ICI-induced myocarditis. Pyroptosis mediated by GSDME, but not the canonical GSDMD, is activated in myocardial tissue of mice and cancer patients with ICI-induced myocarditis. Deficiency of GSDME in male mice alleviates ICI-induced cardiac infiltration of T cells, macrophages, and monocytes, as well as mitochondrial damage and inflammation. Restoration of GSDME expression specifically in cardiomyocytes, rather than myeloid cells, in GSDME-deficient mice reproduces ICI-induced myocarditis. Mechanistically, quantitative proteomics reveal that GSDME-dependent pyroptosis promotes cell death and mitochondrial DNA release, which in turn activates cGAS-STING signaling, triggering a robust interferon response and myocardial immune/inflammation activation. Pharmacological blockade of GSDME attenuates ICI-induced myocarditis and improves long-term survival in mice. Our findings may advance the understanding of ICI-induced myocarditis and suggest that targeting the GSDME-cGAS-STING-interferon axis may help prevent and manage ICI-associated myocarditis.

Drug Interactions between Traditional Chinese Medicines and Cardiovascular Drugs.

Cardiovascular disease (CVD) is one of the leading causes of death worldwide, and its internal medicine treatments are mostly single/few-target chemical drugs. Long-term use of cardiovascular drugs for complex chronic diseases may lead to serious adverse drug reactions. Traditional Chinese medicine (TCM) has been used to treat heart diseases for thousands of years, helping to ease symptoms and prolong patients' lifespan in ancient China. TCM has the pharmacological characteristics of being multi-component, multi-target and multi-pathway, and the combined application of TCM and western medicine can be an alternative treatment for chronic and intractable diseases with high safety levels. This article reviewed the interactions and synergistic effect of TCM and cardiovascular drugs. In the treatment of arrhythmia, TCM combined with western medicine can more effectively regulate patients' cardiac electrophysiological characteristics, reduce the onsets of premature beat and heart rate variability, lower the levels of QT interval dispersion and serum inflammatory factors, alleviate clinical symptoms and TCM syndromes, and improve cardiac function with good safety levels. In the treatment of hypertension, integrative medicine can more steadily reduce blood pressure and levels of serum inflammatory factors and improve hemodynamic indexes and exercise tolerance, and it has high safety levels, especially for pregnant women. As for coronary heart disease, the combination of TCM and antiplatelet drugs may promote the absorption of each other. However, the interaction risk of pharmacokinetic mechanism between them is low at the dose of efficacy. Integrative medicine can reduce the level of N-terminal pro-brain natriuretic peptide, delay cardiac remodeling and improve heart function and quality of life for patients with heart failure with high safety levels.

[Predictive effect of the dual-parametric MRI modified maximum diameter of the lesions with PI-RADS 4 and 5 on the clinically significant prostate cancer].

OBJECTIVE: To assess the rationality of the maximum lesion diameter of 15 mm in prostate imaging reporting and data system (PI-RADS) as a criterion for upgrading a lesion from category 4 to 5 and improve it to enhance the prediction of clinically significant prostate cancer (csPCa). METHODS: In this study, the patients who underwent prostate magnetic resonance imaging (MRI) and prostate biopsy at Peking University First Hospital from 2019 to 2022 as a development cohort, and the patients in 2023 as a validation cohort were reviewed. The localization and maximum diameter of the lesion were fully evaluated. The area under the curve (AUC) and the cut-off value of the maximum diameter of the lesion to predict the detection of csPCa were calculated from the receiver operating characteristics (ROC) curve. Confounding factors were reduced by propensity score matching (PSM). Diagnostic efficacy was compared in the validation cohort. RESULTS: Of the 589 patients in the development cohort, 358 (60.8%) lesions were located in the peripheral zone and 231 (39.2%) were located in the transition zone, and 496 (84.2%) patients detected csPCa. The median diameter of the lesions in the peripheral zone was smaller than that in the transition zone (14 mm vs. 19 mm, P < 0.001). In the ROC analysis of the maximal diameter on the csPCa prediction, there was no statistically significant difference between the peri-pheral zone (AUC=0.709) and the transition zone (AUC=0.673, P=0.585), and the cut-off values were calculated to be 11.5 mm for the peripheral zone and 16.5 mm for the migrating zone. By calcula-ting the Youden index for the cut-off values in the validation cohort, we found that the categorisation by lesion location led to better predictive results. Finally, the net reclassification index (NRI) was 0.170. CONCLUSION: 15 mm as a criterion for upgrading the PI-RADS score from 4 to 5 is reasonable but too general. The cut-off value for peripheral zone lesions is smaller than that in transitional zone. In the future consideration could be given to setting separate cut-off values for lesions in different locations.

Dual-responsive electrochemical immunosensor for CYFRA21-1 detection based on Au/Co Co-loaded 3D ordered macroporous carbon interconnected framework.

Cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) is a protein fragment released into the bloodstream during the death of lung epithelial cells, serving as a predictive biomarker in diagnosing non-small cell lung cancer (NSCLC) and need to be accurately detected. Herein, a dual-responsive label-free electrochemical immunosensor was developed based on a three-dimensional ordered interconnecting macroporous carbon skeleton material modified with gold-cobalt nanoparticles (Au/Co NPs-3D MCF) to detect cytokeratin-19 fragment (CYFRA21-1). The three-dimensional ordered interconnect macroporous structure, by providing a high specific surface area and an electrochemically active area, not only enhances the electron transport channel and reduces mass transfer resistance, but also offers a confined region that elevates the collision frequency with the active site. In addition to exhibiting excellent biocompatibility for antibody binding, gold-cobalt nanoparticles contribute significantly to the overall robustness of the immunosensor. By capitalizing on the 3D network structure and collective effect of Au and Co NPs, the Au/Co NPs-3D MCF immunosensors exhibit exceptional response signals in both chronocurrent testing and square-wave voltammetry, allowing for a wide linear response range of 0.0001-100 ng/mL and a low detection limit. Moreover, the constructed immunosensor is capable of detecting CYFRA21-1 in human serum and has the potential for further extension to detect multiple biomarkers. This work opens up new avenues for the construction of other highly selective 3D network immunosensors.

[Protective effects and mechanisms of berberine hydrochloride on intestinal mucosal barrier injury in rats with sepsis].

OBJECTIVE: To investigate the protective effect of berberine hydrochloride on intestinal mucosal barrier damage in sepsis rats and its mechanism. METHODS: Forty-eight male SD rats were divided into a control group (Sham group, 6 cases), a sepsis model group (LPS group, 14 cases), a berberine hydrochloride intervention group (Ber group, 14 cases), and a Notch signaling pathway inhibition group (DAPT group, 14 cases) according to random number table method. The DAPT group was intraperitoneally injected with 5 mg/kg Notch signaling pathway inhibition DAPT 2 hours before modeling. The sepsis model was established by intraperitoneal injection of 10 mg/kg lipopolysaccharide (LPS); Sham group was injected with an equal amount of saline (2 mL). The Ber group and DAPT group were treated with gavage of 50 mg/kg berberine hydrochloride 2 hours after modeling; Sham group and LPS group were treated with gavage of an equal amount of saline (2 mL). The temperature, weight, behavior and survival rate of rats were observed at 0, 6, 12 and 24 hours of modeling. After 24 hours of modeling, abdominal aortic blood was collected under anesthesia, and intestinal tissues were obtained after euthanasia. The pathological changes of ileum were observed under light microscope. The ultrastructure of ileum was observed under transmission electron microscope. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of serum diamine oxidase (DAO), intestinal fatty acid binding protein (iFABP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Real time-polymerase chain reaction (RT-PCR) and Western blotting were used to detect the mRNA and protein expressions of tight junction proteins (Occludin and Claudin1), Notch1 and their downstream target signals in the ileum tissue. RESULTS: After 24 hours of modeling, compared with the Sham group, the LPS group, Ber group, and DAPT group showed a decrease in weight and an increase in temperature. Among them, the LPS group showed the most significant changes, followed by the DAPT group, and the Ber group showed the least significant changes. The survival rates of the LPS group, Ber group, and DAPT group were all lower than those of the Sham group [42.9% (6/14), 57.1% (8/14), 57.1% (8/14) vs. 100% (6/6)], and six rats were taken from each group for subsequent testing. Macroscopic observation of the intestine showed that the LPS group had the most severe edema in the ileum tissue and abdominal bleeding, with significant improvement in the Ber group and followed by the DAPT group. Under the light microscope, the LPS group showed disordered arrangement of glandular tissue in the ileum mucosa, significantly reduced goblet cells, and extensive infiltration of inflammatory cells, which were significantly improved in the Ber group but less improved in the DAPT group. Under electron microscopy, the LPS group showed extensive shedding of ileal microvilli and severe damage to the tight junction complex structure of intestinal epithelial cells, which was significantly improved in the Ber group but less improved in the DAPT group. The levels of serum DAO, iFABP, TNF-α, IL-6 in the LPS group were significantly higher than those in the Sham group, while the above indicators in the Ber group were significantly lower than those in the LPS group [DAO (µg/L): 4.94±0.44 vs. 6.53±0.49, iFABP (ng/L): 709.67±176.97 vs. 1 417.71±431.44, TNF-α (ng/L): 74.70±8.15 vs. 110.36±3.51, IL-6 (ng/L): 77.34±9.80 vs. 101.65±6.92, all P < 0.01], while the above indicators in the DAPT group were significantly higher than those in the Ber group. The results of RT-PCR and Western blotting showed that the mRNA and protein expressions of Occludin, Claudin1, Notch1, and Hes1 in the ileum tissue of LPS group rats were decreased compared to the Sham group, which were significantly increased in the Ber group compared with the LPS group [mRNA expression: Occludin mRNA (2-ΔΔCt): 1.61±0.74 vs. 0.30±0.12, Claudin1 mRNA (2-ΔΔCt): 1.97±0.37 vs. 0.58±0.14, Notch1 mRNA (2-ΔΔCt): 1.29±0.29 vs. 0.36±0.10, Hes1 mRNA (2-ΔΔCt): 1.22±0.39 vs. 0.27±0.04; protein expression: Occludin/GAPDH: 1.17±0.14 vs. 0.74±0.04, Claudin1/GAPDH: 1.14±0.06 vs. 0.58±0.10, Notch1/GAPDH: 0.87±0.11 vs. 0.56±0.09, Hes1/GAPDH: 1.02±0.13 vs. 0.62±0.01; all P < 0.05], while those in the DAPT group were significantly lower than those in the Ber group. CONCLUSIONS: Early use of berberine hydrochloride can significantly improve intestinal mucosal barrier damage in sepsis rats, and its mechanism may be related to inhibiting inflammatory response and regulating the expression of intestinal mechanical barrier tight junction protein through Notch1 signal.

Comparison of pregnancy outcomes between 4th day morula and 5th day blastocyst after embryo transfer: a retrospective cohort study.

BACKGROUND: This study was designed to evaluate pregnancy outcomes between morulae transferred on day 4 (D4) and blastocysts transferred on day 5 (D5). METHODS: From September 2017 to September 2020, 1963 fresh transfer cycles underwent early follicular phase extra-long protocol for assisted conception in our fertility center were divided into D4 (324 cases) and D5 (1639 cases) groups, and the general situation and other differences of patients in both groups were compared. To compare the differences in pregnancy outcomes, the D4 and D5 groups were further divided into groups A and B based on single and double embryo transfers. Furthermore, the cohort was divided into two groups: those with live births (1116 cases) and those without (847 cases), enabling a deeper evaluation of the effects of D4 or D5 transplantation on assisted reproductive outcomes. RESULTS: In single embryo transfer, there was no significant difference between groups D4A and D5A (P > 0.05). In double embryo transfer, group D4B had a lower newborn birthweight and a larger proportion of low birthweight infants (P < 0.05). The preterm delivery rate, twin delivery rate, cesarean delivery rate, and percentage of low birthweight infants were lower in the D5A group than in the D5B group (P < 0.05). Analysis of factors influencing live birth outcomes further confirmed the absence of a significant difference between D4 and D5 transplantation in achieving live birth (P > 0.05). CONCLUSION: When factors such as working life and hospital holidays are being considered, D4 morula transfer may be a good alternative to D5 blastocyst transfer. Given the in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) success rate and risk of twin pregnancy, D4 morula transfer requires an adapted decision between single and double embryo transfer, although a single blastocyst transfer is recommended for the D5 transfer in order to decrease the twin pregnancy rate. In addition, age, endometrial thickness and other factors need to be taken into account to personalize the IVF program and optimize pregnancy outcomes.

Vanadium-Silsesquioxane Nanocages as Heterogeneous Catalysts for Synthesis of Quinazolinones.

The functionalization of polyoxovanadate clusters is promising but of great challenge due to the versatile coordination geometry and oxidation state of vanadium. Here, two unprecedented silsesquioxane ligand-protected "fully reduced" polyoxovanadate clusters were fabricated via a facial solvothermal methodology. The initial mixture of the two polyoxovanadate clusters with different colors and morphologies (green plate V14 and blue block V6) was successfully separated as pure phases by meticulously controlling the assembly conditions. Therein, the V14 cluster is the highest-nuclearity V-silsesquioxane cluster to date. Moreover, the transformation from a dimeric silsesquioxane ligand-protected V14 cluster to a cyclic hexameric silsesquioxane ligand-protected V6 cluster was also achieved, and the possible mechanism termed "ligand-condensation-involved dissociation reassembly" was proposed to explain this intricate conversion process. In addition, the robust V6 cluster was served as a heterogeneous catalyst for the synthesis of important heterocyclic compounds, quinazolinones, starting from 2-aminobenzamide and aldehydes. The V6 cluster exhibits high activity and selectivity to access pure quinazolinones under mild conditions, where the high selectivity was attributed to the confinement effect of the macrocyclic silsesquioxane ligand constraining the molecular freedom of the reaction species. The stability and recyclability as well as the tolerance of a wide scope of aldehyde substrates endow the V6 cluster with a superior performance and appreciable potential in catalytic applications.

Simultaneous enhanced antibiotic pollutants removal and sustained permeability of the membrane involving CoFe2O4/MoS2 catalyst initiated with simple H2O2 backwashing.

Membranes for wastewater treatment should ideally exhibit sustainable high permeate production, enhanced pollutant removal, and intrinsic physical rejection. In this study, CoFe2O4/MoS2 serves as a non-homogeneous phase catalyst; it is combined with polyether sulfone membranes via liquid-induced phase separation to simultaneously sustain membrane permeability and enhance antibiotic pollutant degradation. The prepared catalytic membranes have higher pure water flux (329.34 L m-2 h-1) than pristine polyethersulfone membranes (219.03 L m-2 h-1), as well as higher mean pore size, porosity, and hydrophilicity. Under a moderate transmembrane pressure (0.05 MPa), tetracycline (TC) in synthetic and real wastewater was degraded by the optimal catalytic membrane by 72.7 % and 91.2 %, respectively. Owing to the generation of the reactive oxygen species (ROS) during the Fenton-like reaction process, the catalytic membrane could exclude the natural organics during the H2O2 backwash step and selectively promote fouling degradation in the membrane channel. The irreversible fouling ratio of the catalyzed membrane was significantly reduced, and the flux recovery rate increased by up to 91.6 %. A potential catalytic mechanism and TC degradation pathways were proposed. This study offers valuable insights for designing catalytic membranes with enhanced filtration performance.

Peripartum outcomes and immune responses after SARS-CoV-2 infection in the third trimester of pregnancy.

BACKGROUND: SARS-CoV-2 infection in pregnant women during the third trimester resulted in overall adverse pregnancy outcomes compared to non-infected controls and a unique humoral and cellular response at delivery. In this study we aimed to assess the impact of SARS-CoV-2 infection on maternal/neonatal peripartum outcomes andimmunological profiles. METHOD: In this study, we recruited 304 SARS-CoV-2 infected pregnant women and 910 SARS-CoV-2 non-infected pregnant women who were admitted for delivery. Peripartum and neonates' outcomes response to SARS-CoV-2 infection were analyzed. Furthermore, we characterized the antibody and cytokines profile in SARS-CoV-2 infected maternal blood (MB) and cord blood (CB). We also assessed routine laboratory tests and liver function tests in MB before labor. Unpaired T test, Mann-Whitney test and Spearman test were used to analyze the data. RESULTS: SARS-CoV-2 infected pregnant women were significantly associated with increased risk of adverse pregnancy outcomes, including preterm labor (13.8% vs. 9.5%, p = 0.033) and meconium-stained amniotic fluid (8.9% vs. 5.5%, p = 0.039). The risk of low birth weight (< 2500 g) (10.5% vs. 6.5%, p = 0.021) and Apgar score < 8 at 1-minute (9.2% vs. 5.8%, p = 0.049) significantly increased in newborns from COVID-19 positive mothers than their counterparts. Our results showed that antibodies were increased in adverse-outcome SARS-CoV-2 infected mothers and their neonates, and abnormal proportion of immune cells were detected in SARS-CoV-2 infected mothers. While the immune response showed no difference between adverse-outcome infected pregnant women and normal-outcome infected pregnant women. Thus, SARS-CoV-2 infection during the third trimester of pregnancy induced a unique humoral and cellular response at delivery. CONCLUSION: SARS-CoV-2 infection closer to delivery could incline to adverse pregnancy outcomes. Therefore, the utmost care is required for SARS-CoV-2 infected pregnant women and their newborns. TRIAL REGISTRATION: The study protocol was approved by the Institutional Review Board of the First Hospital of Jilin University with the approval code number 23K170-001, and informed consent was obtained from all enrolled patients prior to sample collection.

Anemia From Inflammation After Intracerebral Hemorrhage and Relationships With Outcome.

BACKGROUND: Baseline anemia is associated with poor intracerebral hemorrhage (ICH) outcomes. However, underlying drivers for anemia and whether anemia development after ICH impacts clinical outcomes are unknown. We hypothesized that inflammation drives anemia development after ICH and assessed their relationship to outcomes. METHODS AND RESULTS: Patients with serial hemoglobin and iron biomarker concentrations from the HIDEF (High-Dose Deferoxamine in Intracerebral Hemorrhage) trial were analyzed. Adjusted linear mixed models assessed laboratory changes over time. Of 42 patients, significant decrements in hemoglobin occurred with anemia increasing from 19% to 45% by day 5. Anemia of inflammation iron biomarker criteria was met in 88%. A separate cohort of 521 patients with ICH with more granular serial hemoglobin and long-term neurological outcome data was also investigated. Separate regression models assessed whether (1) systemic inflammatory response syndrome (SIRS) scores related to hemoglobin changes over time and (2) hemoglobin changes related to poor 90-day outcome. In this cohort, anemia prevalence increased from 30% to 71% within 2 days of admission yet persisted beyond this time. Elevated systemic inflammatory response syndrome was associated with greater hemoglobin decrements over time (adjusted parameter estimate: -0.27 [95% CI, -0.37 to -0.17]) and greater hemoglobin decrements were associated with poor outcomes (adjusted odds ratio per 1 g/dL increase, 0.76 [95% CI, 0.62-0.93]) independent to inflammation and ICH severity. CONCLUSIONS: We identified novel findings that acute anemia development after ICH is common, rapid, and related to inflammation. Because anemia development is associated with poor outcomes, further work is required to clarify if anemia, or its underlying drivers, are modifiable treatment targets that can improve ICH outcomes. REGISTRATION: https://www.clinicaltrials.gov Unique identifier: NCT01662895.

Identification and characterization of olfactory gene families in Macrobrachium rosenbergii based on full-length transcripts and genome sequences.

The olfactory gene families include odorant binding proteins (OBPs), chemosensory proteins (CSPs), olfactory receptors (ORs), ionotropic receptors (IRs) and gustatory receptors (GRs). To investigate the molecular function of olfactory perception in Macrobrachium rosenbergii, we integrated the full-length transcripts and whole-genome sequences to identify the olfactory gene families. In this study, a total of 38,955 full-length transcripts with an N50 length of 3383 bp were obtained through PacBio SMRT sequencing. Through the annotation of full-length transcripts and whole-genome sequences, several olfactory gene families were identified, including 18 MrORs, 16 MrIRs, 151 MrIGluRs (ionotropic glutamate receptors), 2 MrVIGluRs (variant ionotropic glutamate receptors) and 3 MrCRs (chemosensory receptors). Notably, the CRs were first identified in prawns and shrimps. Additionally, the olfactory gene families in M. nipponense were identified, comprising 4 MnORs, 21 MnIRs, 79 MnIGluRs, 5 MnVIGluRs, 1 MnGR and 1 MnOBP, using the available whole-genome sequences. Meanwhile, the external morphology of the chemical sensory organs of M. rosenbergii was explored, and the presence of plumose setae (PS), hard thorn setae (HTS), bamboo shoot setae (BSS), soft thorn setae (STS) and aesthetascs (AE) on the antennules, HTS and BSS on the second antennae, and PS on the pereiopods were observed by scanning electron microscope. This study provides valuable insights for future functional studies into the olfactory perception of crustaceans and establishes a theoretical basis for molecular design breeding in M. rosenbergii.

Growing in phosphorus-impoverished habitats in south-western Australia: How general are phosphorus-acquisition and -allocation strategies among Proteaceae, Fabaceae and Myrtaceae species?

Numerous phosphorus (P)-acquisition and -utilisation strategies have evolved in plants growing in severely P-impoverished environments. Although these strategies have been well characterised for certain taxa, like Proteaceae, P-poor habitats are characterised by a high biodiversity, and we know little about how species in other families cope with P scarcity. We compared the P-acquisition and leaf P-allocation strategies of Fabaceae and Myrtaceae with those of Proteaceae growing in the same severely P-impoverished habitat. Myrtaceae and Fabaceae exhibited multiple P-acquisition strategies: P-mining by carboxylates or phosphatases, P uptake facilitated by carboxylate-releasing neighbours, and dependence on the elevated soil P availability after fire. Surprisingly, not all species showed high photosynthetic P-use efficiency (PPUE). Highly P-efficient species showed positive correlations between PPUE and the proportion of metabolite P (enzyme substrates), and negative correlations between PPUE and phospholipids (cellular membranes) and nucleic acid P (mostly ribosomal RNA), while we found no correlations in less P-efficient species. Overall, we found that Myrtaceae and Fabaceae used a wider range of strategies than Proteaceae to cope with P scarcity, at both the rhizosphere and leaf level. This knowledge is pivotal to better understand the mechanisms underlying plant survival in severely nutrient-impoverished biodiverse ecosystems.

Au NPs modified Ni-B nanosheets/graphene oxide three-dimensional network as label-free electrochemical immunosensor for the detection of diethylstilbestrol.

Three-dimensional (3D) network provide a promising platform for construction of high sensitive electrochemical immunosensor due to the benefits of high specific surface area and electron mobility. Herein, a sensitive label-free electrochemical immunosensor based on Au nanoparticles modified Ni-B nanosheets/graphene matrix was constructed to detect diethylstilbestrol (DES). The 3D network not only could increase the electron transport rate and surface area, but also could provide confinement area, which is conducive to increases the collision frequency with the active site. Moreover, Au NPs also have good biocompatibility, which is beneficial for ligating antibodies. Benefiting from the 3D network structure and Au collective effect, the electrochemical immunosensor possess sterling detection ability with wide linear response range (0.00038-150 ng/mL) and low detection limit (31.62 fg/mL). Moreover, the constructed immunosensor can also be extend to detect DES in Tap-water and river water. This work may provide a novel material model for the construction of high sensitive immunosensor.

Effects of ketogenic diet on cognitive function of patients with Alzheimer's disease: a systematic review and meta-analysis.

BACKGROUND: Ketogenic diets (KD) have shown remarkable effects in many disease areas. It has been demonstrated in numerous animal experiments that KD is effective in the treatment of Alzheimer's disease (AD). But the clinical effect of treating AD is uncertain. OBJECTIVE: To systematically review the impact of KD on cognitive function in AD. METHODS: We conducted a search of three international databases-PubMed, Cochrane Library, and Embase-to retrieve RCTs on the KD intervention for AD from the inception of the databases through October 2023. Two reviewers searched and screened the literature, extracted and checked relevant data independently, and assessed the risk of bias of the included studies. The meta-analysis was carried out utilizing RevMan 5.3 software. RESULTS: A total of 10 RCTS involving 691 patients with AD were included. There were 357 participants in the intervention group and 334 participants in the control group. The duration of the KD intervention ranged from a minimum of 3 months to a maximum of 15 months. Meta-analysis results showed that KD could effectively improve the mental state of the elderly (NM scale) [MD = 7.56, 95%CI (3.02, 12.10), P = 0.001], MMSE [MD = 1.25, 95%CI (0.46, 2.04), P = 0.002], and ADAS-Cog [MD = -3.43, 95%CI (-5.98, -0.88), P = 0.008]. The elevation of ketone body (ß-hydroxybutyric) [MD = 118.84, 95%CI (15.20, 222.48), P = 0.02] may also lead to the elevation of triglyceride [MD = 0.19, 95%CI (0.03, 0.35), P = 0.02] and low density lipoprotein [MD = 0.31, 95%CI (0.04, 0.58), P = 0.02]. CONCLUSION: Research conducted has indicated that the KD can enhance the mental state and cognitive function of those with AD, albeit potentially leading to an elevation in blood lipid levels. In summary, the good intervention effect and safety of KD are worthy of promotion and application in clinical treatment of AD.