MaHsf24, a novel negative modulator, regulates cold tolerance in banana fruits by repressing the expression of HSPs and antioxidant enzyme genes.

Transcriptional regulation mechanisms underlying chilling injury (CI) development have been widely investigated in model plants and cold-sensitive fruits, such as banana (Musa acuminata). However, unlike the well-known NAC and WRKY transcription factors (TFs), the function and deciphering mechanism of heat shock factors (HSFs) involving in cold response are still fragmented. Here, we showed that hot water treatment (HWT) alleviated CI in harvested banana fruits accomplishing with reduced reactive oxygen species (ROS) accumulation and increased antioxidant enzyme activities. A cold-inducible but HWT-inhibited HSF, MaHsf24, was identified. Using DNA affinity purification sequencing (DAP-seq) combined with RNA-seq analyses, we found three heat shock protein (HSP) genes (MaHSP23.6, MaHSP70-1.1 and MaHSP70-1.2) and three antioxidant enzyme genes (MaAPX1, MaMDAR4 and MaGSTZ1) were the potential targets of MaHsf24. Subsequent electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation coupled with quantitative PCR (ChIP-qPCR) and dual-luciferase reporter (DLR) analyses demonstrated that MaHsf24 repressed the transcription of these six targets via directly binding to their promoters. Moreover, stably overexpressing MaHsf24 in tomatoes increased cold sensitivity by suppressing the expressions of HSPs and antioxidant enzyme genes, while HWT could recover cold tolerance, maintaining higher levels of HSPs and antioxidant enzyme genes, and activities of antioxidant enzymes. In contrast, transiently silencing MaHsf24 by virus-induced gene silencing (VIGS) in banana peels conferred cold resistance with the upregulation of MaHSPs and antioxidant enzyme genes. Collectively, our findings support the negative role of MaHsf24 in cold tolerance, and unravel a novel regulatory network controlling bananas CI occurrence, concerning MaHsf24-exerted inhibition of MaHSPs and antioxidant enzyme genes.

Learning pathways composed of core subjects with features of reducing cognitive load have better learning outcomes.

BACKGROUND: Changing the course duration or timing of subjects in learning pathways would influence medical students' learning outcomes. Curriculum designers need to consider the strategy of reducing cognitive load and evaluate it continuously. Our institution underwent gradual curricular changes characterized by reducing cognitive load since 2000. Therefore, we wanted to explore the impact of this strategy on our previous cohorts. METHODS: This cohort study explored learning pathways across academic years of more than a decade since 2000. Eight hundred eighty-two medical students between 2006 to 2012 were included eventually. Learning outcomes included an average and individual scores of subjects in different stages. Core subjects were identified as those where changes in duration or timing would influence learning outcomes and constitute different learning pathways. We examined whether the promising learning pathway defined as the pathway with the most features of reducing cognitive load has higher learning outcomes than other learning pathways in the exploring dataset. The relationship between features and learning outcomes was validated by learning pathways selected in the remaining dataset. RESULTS: We found nine core subjects, constituting four different learning pathways. Two features of extended course duration and increased proximity between core subjects of basic science and clinical medicine were identified in the promising learning pathway 2012, which also had the highest learning outcomes. Other pathways had some of the features, and pathway 2006 without such features had the lowest learning outcomes. The relationship between higher learning outcomes and cognitive load-reducing features was validated by comparing learning outcomes in two pathways with and without similar features of the promising learning pathway. CONCLUSION: An approach to finding a promising learning pathway facilitating students' learning outcomes was validated. Curricular designers may implement similar design to explore the promising learning pathway while considering potential confounding factors, including students, medical educators, and learning design of the course.

Multiple genetic polymorphisms are associated with the risk of metabolic syndrome, fatty liver, and airflow limitation: A Taiwan Biobank study.

BACKGROUND: Links have been reported between the airflow limitation and both metabolic syndrome (MetS) and fatty liver (FL). Additionally, associations between genetic factors and risks of MetS, FL, and airflow limitation have been identified separately in different studies. Our study aims to simultaneously explore the association between specific single nucleotide polymorphisms (SNPs) of certain genes and the risk of the three associated diseases. METHODS: In this retrospective cross-sectional nationwide study, 150,709 participants from the Taiwan Biobank (TWB) were enrolled. We conducted a genotype-phenotype association analysis of nine SNPs on seven genes (ApoE-rs429358, MBOAT7-rs641738, LEPR-rs1805096, APOC3-rs2854116, APOC3-rs2854117, PPP1R3B-rs4240624, PPP1R3B-rs4841132, TM6SF2-rs58542926, and IFNL4-rs368234815) using data from the TWB1.0 and TWB2.0 genotype dataset. Participants underwent a series of assessments including questionnaires, blood examinations, abdominal ultrasounds, and spirometry examinations. RESULTS: MetS was associated with FL and airflow limitation. ApoE-rs429358, LEPR-rs1805096, APOC3-rs2854116, APOC3-rs2854117, PPP1R3B-rs4240624, PPP1R3B-rs4841132, and TM6SF2-rs58542926 were significantly associated with the risk of MetS. The cumulative impact of T alleles of ApoE-rs429358 and TM6SF2-rs58542926 on the risk of FL was observed (p-value for trend < 0.001). Individuals without MetS and airflow limitation carrying LEPR-rs1805096 G_G genotype exhibited a reduction in the forced expiratory volume in 1 s percentage prediction (Coefficient -35, 95 % confidence interval (CI) -69.7- -0.4), low forced vital capacity percentage prediction (Coefficient -41.6, 95 % CI -82.6- -0.6), and low vital capacity percentage prediction (Coefficient -42.2, 95 % CI -84.2- -0.1). CONCLUSIONS: MetS significantly correlated with FL and airflow limitation. Multiple SNPs were notably associated with MetS. Specifically, T alleles of ApoE-rs429358 and TM6SF2-rs58542926 cumulatively increased the risk of FL. LEPR-rs1805096 shows a trend-wise association with pulmonary function, which is significant in patients without MetS or airflow limitation.

The efficacy of platelet rich plasma in the treatment of erectile dysfunction: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Erectile dysfunction (ED) is a common issue among males, and the use of platelet-rich plasma (PRP) therapy for treating ED has gained increasing attention, but there is still no conclusive evidence regarding its efficacy. AIM: To evaluate the efficacy of PRP therapy for ED. METHODS: We systematically searched PubMed, Embase, Cochrane Library, and Web of Science databases up to November 2023 to identify randomized controlled trials (RCTs) on PRP therapy for ED. We used Review Manager version 5.4 for data analysis and management. RESULT: After applying inclusion and exclusion criteria for screening, a total of 4 studies involving 413 patients were finally included in our meta-analysis. According to our analysis, the PRP group showed significant advantages over the placebo group in terms of MCID at the first month (p = 0.03) and sixth months (p = 0.008), while there was no significant difference between the two groups at the third month (p = 0.19). Additionally, in terms of IIEF, PRP showed significantly better efficacy than placebo at the first, third, and sixth months (p < 0.00001). CONCLUSIONS: PRP shows more effectiveness in treating ED compared to placebo, offering hope as a potential alternative treatment for ED.

A Novel High-Precision Railway Obstacle Detection Algorithm Based on 3D LiDAR.

This article presents a high-precision obstacle detection algorithm using 3D mechanical LiDAR to meet railway safety requirements. To address the potential errors in the point cloud, we propose a calibration method based on projection and a novel rail extraction algorithm that effectively handles terrain variations and preserves the point cloud characteristics of the track area. We address the limitations of the traditional process involving fixed Euclidean thresholds by proposing a modulation function based on directional density variations to adjust the threshold dynamically. Finally, using PCA and local-ICP, we conduct feature analysis and classification of the clustered data to obtain the obstacle clusters. We conducted continuous experiments on the testing site, and the results showed that our system and algorithm achieved an STDR (stable detection rate) of over 95% for obstacles with a size of 15 cm × 15 cm × 15 cm in the range of ±25 m; at the same time, for obstacles of 10 cm × 10 cm × 10 cm, an STDR of over 80% was achieved within a range of ±20 m. This research provides a possible solution and approach for railway security via obstacle detection.

Sex differences in direction giving: Are boys better than girls?

Previous research has extensively documented sex differences favoring boys in various domains of spatial cognition. However, relatively little research has examined sex differences in children's direction giving. The current study aimed to bridge this gap. A total of 143 children aged 3 to 10 years were asked to describe and recall routes from survey perspectives (via maps) and route perspectives (via videos). Significant sex effects (favoring boys) in direction-giving accuracy were found in describing route trials. However, boys and girls did not differ in the frequency of utterances encoding landmarks and direction of turns, suggesting that the quality rather than the quantity of words played a more important role in explaining sex differences. In addition, there was no sex difference in the route recall task. Although accuracy was overall higher in the map condition than in the video condition, it did not moderate sex differences. Overall, our study showed a robust sex difference in direction giving, which has important theoretical implications for understanding the development of human sex differences and critical clinical implications for designing training programs to improve children's spatial cognition.

Optimal body mass index for protecting middle-aged and elderly patients with fatty liver from future fractures.

OBJECTIVE: Previous studies have suggested that body mass index (BMI) should be considered when assessing the relationship between fatty liver (FL) and osteoporosis. The aim of this study was to investigate future fracture events in people with FL, focusing on the effect of BMI in both sexes. METHODS: This retrospective cohort study from 2011 to 2019 enrolled 941 people, including 441 women and 500 men, aged 50 years or older who underwent liver imaging (ultrasound, computed tomography, or magnetic resonance image) and dual-energy X-ray absorptiometry (DXA, for bone mineral density measurements). The study examined predictors of osteoporosis in both sexes, and the effect of different ranges of BMI (18.5-24, 24-27, and ≥27 kg/m2 in women; 18.5-24, 24-27, 27-30 and ≥30 kg/m2 in men) on the risk of future fractures in FL patients. RESULTS: The average follow-up period was 5.3 years for women and 4.2 years for men. Multivariate analysis identified age and BMI as independent risk factors for osteoporosis in both sexes. Each unit increase in BMI decreased the risk of osteoporosis by ≥10%. In both women and men with FL, a BMI of 24-27 kg/m2 offered protection against future fractures, compared to those without FL and with a BMI of 18.5-24 kg/m2. CONCLUSION: The protective effect of a higher BMI against future fractures in middle-aged and elderly women and men with FL is not uniform and decreases beyond certain BMI ranges.

Immediate- or Delayed-Intensive Statin in Acute Cerebral Ischemia: The INSPIRES Randomized Clinical Trial.

Importance: Comparisons are limited for immediate-intensive and delayed-intensive statin for secondary stroke prevention and neuroprotection in patients with acute mild ischemic stroke or transient ischemic attack (TIA) from atherosclerosis. Objective: To estimate whether immediate-intensive statin therapy is safe and can lower the risk of recurrent stroke compared with delayed-intensive statin in patients with acute mild ischemic stroke or high-risk TIA from atherosclerosis. Design, Setting, and Participants: The Intensive Statin and Antiplatelet Therapy for High-Risk Intracranial or Extracranial Atherosclerosis (INSPIRES) trial, a double-blind, placebo-controlled, 2 × 2 factorial, randomized clinical trial enrolled patients from September 2018 to October 2022. The trial was conducted at 222 hospitals in China. Patients aged 35 to 80 years with mild ischemic stroke or high-risk TIA of presumed atherosclerosis within 72 hours of symptom onset were assessed. Interventions: Patients were randomly assigned to receive immediate-intensive atorvastatin (80 mg daily on days 1-21; 40 mg daily on days 22-90) or 3-day delayed treatment (placebo for days 1-3, followed by placebo and atorvastatin, 40 mg daily on days 4-21, and then atorvastatin, 40 mg daily on days 22-90). Main Outcomes and Measures: The primary efficacy outcome was new stroke within 90 days, and a secondary efficacy outcome was poor functional outcome. Moderate to severe bleeding was the primary safety outcome. Results: A total of 11 431 patients were assessed for eligibility, and 6100 patients (median [IQR] age, 65 [57-71] years; 3915 men [64.2%]) were enrolled, with 3050 assigned to each treatment group. Within 90 days, new stroke occurred in 245 patients (8.1%) in the immediate-intensive statin group and 256 patients (8.4%) in the delayed group (hazard ratio, 0.95; 95% CI, 0.80-1.13). Poor functional outcome occurred in 299 patients (9.8%) and 348 patients (11.4%) in the immediate-intensive and delayed-intensive statin groups, respectively (odds ratio, 0.83; 95% CI, 0.71-0.98). Moderate to severe bleeding occurred in 23 of 3050 patients (0.8%) and 17 of 3050 patients (0.6%), in the immediate-intensive and delayed-intensive statin groups, respectively. Conclusions and Relevance: Immediate-intensive statin initiated within 72 hours did not reduce the risk of stroke within 90 days and may be associated with improved functional outcomes without significant difference in moderate to severe bleeding, compared with 3-day delayed-intensive statin in Chinese patients with acute mild ischemic stroke or TIA from atherosclerosis. Trial Registration: ClinicalTrials.gov Identifier: NCT03635749.

Picometer-Scale Atomic Shifts Governing Subdisordered Structures in Diamond.

Diamond is considered the most promising next-generation semiconductor material due to its excellent physical characteristics. It has been more than three decades since the discovery of a special structure named n-diamond. However, despite extensive efforts, its crystallographic structure and properties are still unclear. Here, we show that subdisordered structures in diamond provide an explanation for the structural feature of n-diamond. Monocrystalline diamond with subdisordered structures is synthesized via the chemical vapor deposition method. Atomic-resolution scanning transmission electron microscopy characterizations combined with the picometer-precision peak finder technology and diffraction simulations reveal that picometer-scale shifts of atoms within cells of diamond govern the subdisordered structures. First-principles calculations indicate that the bandgap of diamond decreases rapidly with increasing shifting distance, in accordance with experimental results. These findings clarify the crystallographic structure and electronic properties of n-diamond and provide new insights into the bandgap adjustment in diamond.

Inhibitory activities of five fungicides on Alternaria suffruticosae and their field control efficacy against tree peony black spot.

Tree peony black spot (TPBS), mainly caused by Alternaria suffruticosae, is a common leaf disease on the ornamental peony, which posed a great threat on the flower buds in the current year and the flowering quality in the next year. However, there was only one fungicide registered for the control of the disease, difenoconazole. In order to avoid the severe problem of pathogen resistance caused by long-term use of difenoconazole, it is necessary to screen more chemical fungicides for the prevention and control of TPBS. In the paper, the biological activities of flutolanil, phenamacril, pyraclostrobin, and boscalid on mycelial growth, conidial germination, germ tube elongation and sporulation quantity of A. suffruticosae were determined, and field control efficacy were conducted to evaluate the preventive and therapeutic activities. Difenoconazole, was used as a control simultaneously. The results showed that pyraclostrobin had the strongest inhibitory effects on the conidial germination, mycelium growth, germ tube elongation and sporulation quantity, with the average EC50 of 0.0517, 0.5343, 0.0008 and 0.8068 µg/mL respectively. The inhibitory activity of flutolanil on the four developmental stages of A. suffruticosae was weaker than the other three fungicides. Compared with flutolanil, boscalid, the other succinate dehydrogenase inhibitors, had more srtong inhibitory effects on the mycelial growth and sporulation quantity, with the average EC50 of 3.8603 and 1.4760 µg/mL respectively. Phenamacril had a moderate inhibitory level, which had more inhibitory activity on conidial germination and germ tube elongation, with the average EC50 of 31.5349 and 5.2597 µg/mL. All of the four fungicides had no significant effects on the shape of spores and germ tubes. The control fungicide difenoconazole had the strongest inhibitory activity on mycelial growth, and the average EC50 was only 0.3297 µg/ml. However, its inhibitory activity on the other three growth stages was not high. In the field trials, pyraclostrobin had high control efficacy on TPBS even at low concentrations, reaching a minimum of 62.6293%, which was higher than that of difenoconazole. The other three fungicides had higher control efficacy at high concentrations, but decreased significantly at low concentrations. Considering the dosage and control efficacy, pyraclostrobin was the first choice for the control of TPBS. Pyraclostrobin is the preferred alternative fungicide of difenoconazole for the prevention and control of TPBS in production.

Positive fluid balance and poor outcomes after initial intensive care unit admission in sepsis resuscitation: a retrospective study.

Introduction: Fluid resuscitation of patients with sepsis is crucial. This study explored the role of fluid balance in the early resuscitation of sepsis patients in the intensive care unit (ICU). Material and methods: A retrospective study of patients with sepsis using the Peking Union Medical College Hospital Intensive Care Medical Information System and Database from January 2014 to June 2020 was performed. Based on the survival status on day 28, the training cohort was divided into an alive group (n = 1,803) and a deceased group (n = 429). Univariate and multivariate analyses were used to identify risk factors, and the integrated learning XGBoost algorithm was used to construct a model for predicting outcomes. ROC and Kaplan-Meier survival curves were used to evaluate the effectiveness of the model. A verification cohort (n = 433) was used to verify the model. Results: Univariate analysis showed that fluid balance is an important covariate. Based on the scatterplot distribution, a significant difference in mortality was determined between groups stratified with a balance of 1000 ml. There were associations in the multivariate analysis between poor outcomes and sex, PO2/FiO2, serum creatinine, FiO2, platelets, respiratory rate, SPO2, temperature, and total fluid volume (1000 ml). Among these variables, total fluid balance (1000 ml) had an OR of 1.98 (CI: 1.41-2.77, p < 0.001). Therefore, the model was built with these nine factors using XGBoost. Cross validation was used to verify generalizability. This model performed better than the SOFA and APACHE II models. The result was well verified in the verification cohort. A causal forest model suggested that patients with hypoxemia may suffer from positive fluid balance. Conclusions: Sepsis fluid resuscitation in the ICU should be a targeted and goal-oriented treatment. A new prognostic prediction model was constructed and indicated that a 6-hour positive fluid balance after ICU initial admission is a risk factor for poor outcomes in sepsis patients. A 6-hour fluid balance above 1000 ml should be performed with caution.

Effectiveness and safety of Sanhan Huashi granules versus nirmatrelvir-ritonavir in adult patients with COVID-19: A randomized, open-label, multicenter trial.

Sanhan Huashi granules (SHG) demonstrated therapeutic effects against coronavirus disease 2019 (COVID-19) in observational studies. In order to compare the effectiveness and safety of SHG and nirmatrelvir-ritonavir in treating adults with mild-to-moderate COVID-19, we conducted a randomized, active-controlled, open-label, multi-center trial conducted between February and July in 2023. The patients were randomized in a 1:1 ratio to the SHG group and the nirmatrelvir-ritonavir group. A total of 400 participants were randomized, among which 200 participants ultimately received SHG and 198 received nirmatrelvir-ritonavir. The primary outcome was time to sustained clinical recovery through day 28. SHG significantly shortened the median time to sustained clinical recovery compared to nirmatrelvir-ritonavir (6.0 (95% CI, 5.0 to 6.0) vs. 8.0 (95% CI, 6.0 to 9.0) d; P = 0.001), particularly for individual symptoms including fever, sore throat, cough and fatigue. No participants in either group died and incidence of severe COVID-19 showed no difference between two groups. Participants who received nirmatrelvir-ritonavir demonstrated a higher rate of virus clearance on day 5 compared to those received SHG (46.4% (95% CI, 39.1 to 53.7) vs. 65.6% (95% CI, 58.3 to 72.4); P < 0.001). Most adverse events were mild in both groups. In summary, SHG was superior to nirmatrelvir-ritonavir in shortening the time to sustained clinical recovery in participants with mild-to-moderate COVID-19, despite a lower virus clearance rate observed after 5 d of treatment (Chinese Clinical Trial Registry Identifier: ChiCTR2300067872).

Efficacy of collagenase Clostridium histolyticum combination therapies for Peyronie's disease: a systematic review and meta-analysis.

INTRODUCTION: Peyronie's disease (PD) is a common penile disorder characterized by the formation of fibrous noncompliant hard nodules in the tunica albuginea of the penis. Collagenase Clostridium histolyticum (CCH) is an injectable drug that treats PD by enzymatically degrading plaque interstitial collagen. CCH has been used in patients with varying curvature, as well as in the acute and stable phases of the disease, through a variety of treatment regimens and combinations. We carried out a systematic review and meta-analysis to assess the efficacy of CCH combination therapies for PD. METHODS: We selected 4 observational comparative studies and 3 randomized controlled trials including 532 participants from the PubMed, Embase, and Cochrane databases (until December 2023) to evaluate the efficacy of CCH combination therapies for PD. The primary outcome was clinical efficacy as evaluated by improvement in penile curvature and penile length, as well as by scores on the Peyronie's Disease Questionnaire (PDQ) for symptom bother, penile pain, and psychological symptoms. Continuous data were represented by mean difference (MD) and 95% CI. All data were analyzed by Review Manager version 5.3. RESULTS: For penile length (MD, 0.81 cm; 95% CI, 0.17-1.45; P = .01), PDQ symptom bother (MD, -1.02; 95% CI, -1.83 to -0.21; P = .01), and PDQ penile pain (MD, -0.93; 95% CI, -1.50 to -0.36; P = .001), CCH combination therapy showed significantly greater improvements vs CCH monotherapy. However, in the other indicators, penile curvature and PDQ psychological symptoms, there was no significant difference between the therapies. CONCLUSION: This meta-analysis supports that CCH combination therapies can partially increase penile length and ameliorate symptom bother and penile pain to some extent. However, CCH combination therapies still need to be evaluated through more high-quality research.

Buildup and synchronization regimes of a vector pure-quartic soliton molecule in a fiber laser cavity.

Pure-quartic solitons (PQSs) have recently received increasing attention due to their energy-width scaling over the traditional soliton, which has expanded our understanding of soliton dynamics with high-order dispersion in nonlinear systems. Here, we numerically reveal the asynchronization and synchronization processes of the sub-pulse within the vector PQS molecule in a mode-locked fiber laser by solving the coupled Ginzburg-Landau equations. During the establishment of a vector PQS molecule, the repulsion, attraction, and finally stabilization processes have been observed. Specifically, sub-pulse disappearance, regeneration, and finally synchronization with the other pulses are also investigated. Our analysis of the pulse energy, time interval, and relative phase evolution dynamics with the round trip indicates that the asynchronization and synchronization within the vector PQS molecule associate tightly with the gain competition and the cross-phase modulation. Our findings provide insights into the internal mutual dynamics within the vector soliton molecule and offer guidance for the applications of PQS.

Minimizing Voltage Losses via Synergistically Reducing Hetero-Interface Energy Offset for High Efficiency Perovskite Solar Cells.

The open circuit voltage (VOC) losses at multiple interfaces within perovskite solar cells (PSCs) limit the improvements in power conversion efficiency (PCE). Herein, a tailored strategy is proposed to reduce the energy offset at both hetero-interfaces within PSCs to decrease the VOC losses. For the interface of perovskite and electron transport layer where exists a mass of defects, it uses the pyromellitic acid to serve as a molecular bridge, which reduces non-radiative recombination and energy level offset. For the interface of perovskite and hole transport layer, which includes a passivator of PEAI, the detrimental effect (negative shift of work function) of PEAI passivation and optimizing the interface energy level alignment are neutralized by incorporating (2-(4-(bis(4-methoxyphenyl)amino)phenyl)-1-cyanovinyl)phosphonic acid. Owing to synergistically reduced hetero-interface energy offset, the PSCs achieve a PCE of 25.13%, and the VOC is increased from 1.134 to 1.174 V. In addition, the resulting PSCs possess enhanced stability, the unencapsulated PSCs can maintain ≈96% and ≈97% of their initial PCE after 2000 h of aging under ambient conditions and 210 h under operation conditions.

Prognostic value of neutrophil-to-lymphocyte ratio dynamics in patients with septic acute kidney injury: a cohort study.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) has been suggested to be a prognostic marker for various diseases, but whether NLR dynamics (ΔNLR) is related to mortality and disease severity in patients with septic acute kidney injury (AKI) has not been determined. METHODS: Between August 2013 and August 2021, septic AKI patients at our center were retrospectively enrolled. ΔNLR was defined as the difference between the NLR at septic AKI diagnosis and at hospital admission. The relationship between the ΔNLR and mortality was evaluated by Kaplan-Meier curves, Cox proportional hazards, and cubic spline analyses. The prediction values were compared by area under the receiver-operating characteristic curve (AUROC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) analyses. RESULTS: Of the 413 participants, the mean age was 63 ± 17 years, and 134 were female (32.4%). According to the median value, patients in the high-ΔNLR group had significantly greater 90-d mortality (74.4% vs. 46.6%, p < 0.001). After adjustment for potential confounders, high ΔNLR remained an independent predictor of 90-d mortality (HR = 2.80; 95% CI = 1.74-4.49, p < 0.001). Furthermore, ΔNLR had the highest AUROC for 90-d mortality (0.685) among the various biomarkers and exhibited an improved NRI (0.314) and IDI (0.027) when incorporated with PCT and CRP. For secondary outcomes, patients with high ΔNLR had increased risk of 30-d mortality (p = 0.004), need for renal replacement therapy (p = 0.011), and developing stage-3 AKI (p = 0.040) according to the adjusted models. CONCLUSIONS: High ΔNLR is independently associated with increased risk of patient mortality and adverse outcomes. ΔNLR might be utilized to facilitate risk stratification and optimize septic AKI management.

Panax notoginseng saponins prevent dementia and oxidative stress in brains of SAMP8 mice by enhancing mitophagy.

BACKGROUND: Mitochondrial dysfunction is one of the distinctive features of neurons in patients with Alzheimer's disease (AD). Intraneuronal autophagosomes selectively phagocytose and degrade the damaged mitochondria, mitigating neuronal damage in AD. Panax notoginseng saponins (PNS) can effectively reduce oxidative stress and mitochondrial damage in the brain of animals with AD, but their exact mechanism of action is unknown. METHODS: Senescence-accelerated mouse prone 8 (SAMP8) mice with age-related AD were treated with PNS for 8 weeks. The effects of PNS on learning and memory abilities, cerebral oxidative stress status, and hippocampus ultrastructure of mice were observed. Moreover, changes of the PTEN-induced putative kinase 1 (PINK1)-Parkin, which regulates ubiquitin-dependent mitophagy, and the recruit of downstream autophagy receptors were investigated. RESULTS: PNS attenuated cognitive dysfunction in SAMP8 mice in the Morris water maze test. PNS also enhanced glutathione peroxidase and superoxide dismutase activities, and increased glutathione levels by 25.92% and 45.55% while inhibiting 8-hydroxydeoxyguanosine by 27.74% and the malondialdehyde production by 34.02% in the brains of SAMP8 mice. Our observation revealed the promotion of mitophagy, which was accompanied by an increase in microtubule-associated protein 1 light chain 3 (LC3) mRNA and 70.00% increase of LC3-II/I protein ratio in the brain tissues of PNS-treated mice. PNS treatment increased Parkin mRNA and protein expression by 62.80% and 43.80%, while increasing the mRNA transcription and protein expression of mitophagic receptors such as optineurin, and nuclear dot protein 52. CONCLUSION: PNS enhanced the PINK1/Parkin pathway and facilitated mitophagy in the hippocampus, thereby preventing cerebral oxidative stress in SAMP8 mice. This may be a mechanism contributing to the cognition-improvement effect of PNS.

Recent development and fighting strategies for lincosamide antibiotic resistance.

SUMMARYLincosamides constitute an important class of antibiotics used against a wide range of pathogens, including methicillin-resistant Staphylococcus aureus. However, due to the misuse of lincosamide and co-selection pressure, the resistance to lincosamide has become a serious concern. It is urgently needed to carefully understand the phenomenon and mechanism of lincosamide resistance to effectively prevent and control lincosamide resistance. To date, six mobile lincosamide resistance classes, including lnu, cfr, erm, vga, lsa, and sal, have been identified. These lincosamide resistance genes are frequently found on mobile genetic elements (MGEs), such as plasmids, transposons, integrative and conjugative elements, genomic islands, and prophages. Additionally, MGEs harbor the genes that confer resistance not only to antimicrobial agents of other classes but also to metals and biocides. The ultimate purpose of discovering and summarizing bacterial resistance is to prevent, control, and combat resistance effectively. This review highlights four promising strategies, including chemical modification of antibiotics, the development of antimicrobial peptides, the initiation of bacterial self-destruct program, and antimicrobial stewardship, to fight against resistance and safeguard global health.

Using machine learning to identify key subject categories predicting the pre-clerkship and clerkship performance: 8-year cohort study.

BACKGROUND: Medical students need to build a solid foundation of knowledge to become physicians. Clerkship is often considered the first transition point, and clerkship performance is essential for their development. We hope to identify subjects that could predict the clerkship performance, thus helping medical students learn more efficiently to achieve high clerkship performance. METHODS: This cohort study collected background and academic data from medical students who graduated between 2011 and 2019. Prediction models were developed by machine learning techniques to identify the affecting features in predicting the pre-clerkship performance and clerkship performance. Following serial processes of data collection, data preprocessing before machine learning, and techniques and performance of machine learning, different machine learning models were trained and validated using the 10-fold cross-validation method. RESULTS: Thirteen subjects from the pre-med stage and 10 subjects from the basic medical science stage with an area under the ROC curve (AUC) >0.7 for either pre-clerkship performance or clerkship performance were found. In each subject category, medical humanities and sociology in social science, chemistry, and physician scientist-related training in basic science, and pharmacology, immunology-microbiology, and histology in basic medical science have predictive abilities for clerkship performance above the top tertile. Using a machine learning technique based on random forest, the prediction model predicted clerkship performance with 95% accuracy and 88% AUC. CONCLUSION: Clerkship performance was predicted by selected subjects or combination of different subject categories in the pre-med and basic medical science stages. The demonstrated predictive ability of subjects or categories in the medical program may facilitate students' understanding of how these subjects or categories of the medical program relate to their performance in the clerkship to enhance their preparedness for the clerkship.