Pt─O Bond Accelerated Cu0/Cu+ Activity for Boosting Low-Energy Bipolar Hydrogen Production.

To address the imperative challenge of producing hydrogen in a low-energy consumption electrocatalytic system, this study emphasizes the utilization of thermodynamically favorable biomass oxidation for achieving energy-efficient hydrogen generation. This research integrates ultralow PtO2-loaded flower-like nanosheets (denoted as PtO2@Cu2O/Cu FNs) with Cu0/Cu+ pairs and Pt─O bonds, thereby yielding substantial enhancement in both hydrogen evolution reaction (HER, -0.042 VRHE at 10 mA cm-2) and furfural oxidation reaction (FFOR, 0.09 VRHE at 10 mA cm-2). As validated by DFT calculations, the dual built-in electric field (BIEF) is elucidated as the driving force behind the enhanced activities, in which Pt─O bonds expedite the HER, while Cu+/Cu0 promotes low-potential FFOR. By coupling the FFOR and HER together, the resulting bipolar-hydrogen production system requires a low power input (0.5072 kWh per m3) for producing H2. The system can generate bipolar hydrogen and high value-added furoic acid, significantly enhancing hydrogen production efficiency and concurrently mitigating energy consumption.

Reservoir-computing based associative memory and itinerancy for complex dynamical attractors.

Traditional neural network models of associative memories were used to store and retrieve static patterns. We develop reservoir-computing based memories for complex dynamical attractors, under two common recalling scenarios in neuropsychology: location-addressable with an index channel and content-addressable without such a channel. We demonstrate that, for location-addressable retrieval, a single reservoir computing machine can memorize a large number of periodic and chaotic attractors, each retrievable with a specific index value. We articulate control strategies to achieve successful switching among the attractors, unveil the mechanism behind failed switching, and uncover various scaling behaviors between the number of stored attractors and the reservoir network size. For content-addressable retrieval, we exploit multistability with cue signals, where the stored attractors coexist in the high-dimensional phase space of the reservoir network. As the length of the cue signal increases through a critical value, a high success rate can be achieved. The work provides foundational insights into developing long-term memories and itinerancy for complex dynamical patterns.

Regulation of biofilm gene expression by DNA replication in Bacillus subtilis.

Bacillus subtilis relies on biofilms for survival in harsh environments. Extracellular polymeric substance (EPS) is a crucial component of biofilms, yet the dynamics of EPS production in single cells remain elusive. To unveil the modulation of EPS synthesis, we built a minimal network model comprising the SinI-SinR-SlrR module, Spo0A, and EPS. Stochastic simulations revealed that antagonistic interplay between SinI and SinR enables EPS production in bursts. SlrR widens these bursts and increases their frequency by stabilizing SinR-SlrR complexes and depleting free SinR. DNA replication and chromosomal positioning of key genes dictate pulsatile changes in the slrR:sinR gene dosage ratio (gr) and Spo0A-P levels, each promoting EPS production in distinct phases of the cell cycle. As the cell cycle lengthens with nutrient stress, the duty cycle of gr pulsing decreases, whereas the amplitude of Spo0A-P pulses elevates. This coordinated response facilitates keeping a constant proportion of EPS-secreting cells within colonies across diverse nutrient conditions. Our results suggest that bacteria may 'encode' eps expression through strategic chromosomal organization. This work illuminates how stochastic protein interactions, gene copy number imbalance, and cell-cycle dynamics orchestrate EPS synthesis, offering a deeper understanding of biofilm formation.

A novel endocardial activation-derived predictor for focal paraseptal atrial tachycardias: evidence from a multicenter cohort study.

BACKGROUND: The electrocardiogram-based algorithm for predicting para-septal atrial tachycardia (PSAT) is limited by the significant overlaps in the P-wave morphology originating from various para-septal sites. OBJECTIVE: The aim of this study was to investigate the endocardial activation characteristics of PSAT and to seek an endocardial activation-derived predictor for the ablation site. METHODS: Forty-four patients (11 males, average 62.6±14.7 years) with PSAT ablation in four tertiary medical centers were assigned into three groups according to the ablation site: right atrial (RA) para-Hisian region (Group 1, n=10), the noncoronary cusp (NCC) (Group 2, n=13) and left atrial (LA) para-septal areas (Group 3, n=21). Multiple-chamber activation mapping was performed guided by a 3D navigation system. The discrepancies in the earliest activation time between two of three chambers (ΔRA-LA, ΔRA-NCC and ΔLA-NCC) were calculated in each group and used for pairwise comparisons. RESULTS: There was significant difference in ΔRA-LA, ΔRA-NCC, and ΔLA-NCC compared among three groups. ΔRA-LA was the only parameter which could consistently predict the ablation site of PSAT with good accuracy (AUC 1.000, sensitivity 100%/ specificity 100%, and cut-off value 7ms for predicting right para-Hisian or NCC ablation; AUC 0.974, sensitivity 92.3%/specificity 95.2%, and cut-off value -4 ms for predicting NCC or left para-septal ablation). Based on two cut-off values, A two-step algorithm was developed to predict the ablation site of PSAT with positive predictive value of 95.4% and negative predictive value of 97.0%. CONCLUSIONS: ΔRA-LA is a useful endocardial activation-derived parameter for predicting the successful ablation site of PSAT.

Transmission of human-pet antibiotic resistance via aerosols in pet hospitals of Changchun.

In recent years, aerosols have been recognized as a prominent medium for the transmission of antibiotic-resistant bacteria and genes. Among these, particles with a particle size of 2 µm (PM2.5) can directly penetrate the alveoli. However, the presence of antibiotic-resistant genes in aerosols from pet hospitals and the potential risks posed by antibiotic-resistant bacteria in these aerosols to humans and animals need to be investigated. In this study, cefotaxime-resistant bacteria were collected from 5 representative pet hospitals in Changchun using a Six-Stage Andersen Cascade Impactor. The distribution of bacteria in each stage was analyzed, and bacteria from stage 5 and 6 were isolated and identified. Minimal inhibitory concentrations of isolates against 12 antimicrobials were determined using broth microdilution method. Quantitative Polymerase Chain Reaction was employed to detect resistance genes and mobile genetic elements that could facilitate resistance spread. The results indicated that ARBs were enriched in stage 5 (1.1-2.1 µm) and stage 3 (3.3-4.7 µm) of the sampler. A total of 159 isolates were collected from stage 5 and 6. Among these isolates, the genera Enterococcus spp. (51%), Staphylococcus spp. (19%), and Bacillus spp. (14%) were the most prevalent. The isolates exhibited the highest resistance to tetracycline and the lowest resistance to cefquinome. Furthermore, 56 (73%) isolates were multidrug-resistant. Quantitative PCR revealed the expression of 165 genes in these isolates, with mobile genetic elements showing the highest expression levels. In conclusion, PM2.5 from pet hospitals harbor a significant number of antibiotic-resistant bacteria and carry mobile genetic elements, posing a potential risk for alveolar infections and the dissemination of antibiotic resistance genes.

Neoadjuvant camrelizumab plus apatinib for locally advanced microsatellite instability-high or mismatch repair-deficient colorectal cancer (NEOCAP): a single-arm, open-label, phase 2 study.

BACKGROUND: PD-1 blockade is highly efficacious for mismatch repair-deficient colorectal cancer in both metastatic and neoadjuvant settings. We aimed to explore the activity and safety of neoadjuvant therapy with PD-1 blockade plus an angiogenesis inhibitor and the feasibility of organ preservation in patients with locally advanced mismatch repair-deficient colorectal cancer. METHODS: We initiated a single-arm, open-label, phase 2 trial (NEOCAP) at Sun Yat-sen University Cancer Center and the Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China. Patients aged 18-75 years with untreated mismatch repair-deficient or microsatellite instability-high or POLE/POLD1-mutated locally advanced colorectal cancer (cT3 or N+ for rectal cancer, and T3 with invasion ≥5mm or T4, with or without N+ for colon cancer) and an Eastern Cooperative Oncology Group performance score of 0-1 were enrolled and given 200 mg camrelizumab intravenously on day 1 and 250 mg apatinib orally from day 1-14, every 3 weeks for 3 months followed by surgery or 6 months if patients did not have surgery. Patients who had a clinical complete response did not undergo surgery and proceeded with a watch-and-wait approach. The primary endpoint was the proportion of patients with a pathological or clinical complete response. Eligible enrolled patients who received at least one cycle of neoadjuvant treatment and had at least one tumour response assessment following the baseline assessment were included in the activity analysis, and patients who received at least one dose of study drug were included in the safety analysis. The study is registered with ClinicalTrials.gov (NCT04715633) and is ongoing. FINDINGS: Between Sept 29, 2020, and Dec 15, 2022, 53 patients were enrolled; one patient was excluded from the activity analysis because they were found to be mismatch repair-proficient and microsatellite-stable. 23 (44%) patients were female and 29 (56%) were male. The median follow-up was 16·4 (IQR 10·5-23·5) months. 28 (54%; 95% CI 35-68) patients had a clinical complete response and 24 of these patients were managed with a watch-and-wait approach, including 20 patients with colon cancer and multiple primary colorectal cancer. 23 (44%) of 52 patients underwent surgery for the primary tumour, and 14 (61%; 95% CI 39-80) had a pathological complete response. 38 (73%; 95% CI 59-84) of 52 patients had a complete response. Grade 3-5 adverse events occurred in 20 (38%) of 53 patients; the most common were increased aminotransferase (six [11%]), bowel obstruction (four [8%]), and hypertension (four [8%]). Drug-related serious adverse events occurred in six (11%) of 53 patients. One patient died from treatment-related immune-related hepatitis. INTERPRETATION: Neoadjuvant camrelizumab plus apatinib show promising antitumour activity in patients with locally advanced mismatch repair-deficient or microsatellite instability-high colorectal cancer. Immune-related adverse events should be monitored with the utmost vigilance. Organ preservation seems promising not only in patients with rectal cancer, but also in those with colon cancer who have a clinical complete response. Longer follow-up is needed to assess the oncological outcomes of the watch-and-wait approach. FUNDING: The National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, and the Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Exercise interventions for frail older adults with diabetes: A scoping review.

There is a paucity of evidence on exercise interventions for frail older adults with diabetes. This scoping review aims to identify the scope of the current literature on the characteristics and effects of exercise interventions for frail older adults with diabetes. A search without time limitation was conducted in eight databases. 14 studies were finally included. Resistance exercise and multicomponent exercise were the most common types of exercise. There was considerable variation in the frequency, duration and intensity of exercise interventions. Studies reported improvements in frailty status, physical function, blood glucose and lipid levels and economic effectiveness. The most frequent combined interventions involved nutrition and education. Although evidence was limited, the potential benefits of exercise interventions for frail older adults with diabetes were substantial. Further high-quality studies are needed to explore the most effective and cost-saving exercise interventions for frail older adults with diabetes.

Transcutaneous Electrical Acupoint Stimulation Combined with Moderate Sedation of Remimazolam Tosilate in Gastrointestinal Endoscopy: A Prospective, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

INTRODUCTION: Further clinical validation is required to determine whether transcutaneous electrical acupoint stimulation (TEAS) can replace opioids and be used in combination with remimazolam for sedation during gastrointestinal endoscopy. METHODS: A total of 108 outpatients who underwent diagnostic gastrointestinal endoscopy were randomly divided into three groups: fentanyl plus remimazolam group (group C), TEAS plus remimazolam group (group E), and placebo-TEAS plus remimazolam group (group P). The assessments of patient satisfaction, physician satisfaction, and pain scale score during the examination constituted the primary endpoints of the study. The secondary endpoints were the time of recovery, recovery of normal behavioral function and discharge, incidence of adverse reactions, and dose of remimazolam. RESULTS: Compared with group C, group E had a greater median score for patient satisfaction at follow-up and a slightly lower median score for physician satisfaction. The pain score of group E was slightly greater than that of group C, but the difference was not significant. However, in group C, the incidence of hypoxemia, the rate of nausea and the severity of vertigo were greater, and the number of patients discharged and resuming normal behavioral function was greater than those in the other two groups. The dose of remimazolam in group C and group E was less than that in group P. CONCLUSIONS: TEAS combined with moderate sedation of remimazolam can provide an ideal sedative effect, which preferably suppresses discomfort caused by gastrointestinal endoscopy and has fewer sedation-related complications. TRIAL REGISTRATION: ID: NCT05485064; First registration (29/07/2022); Last registration (02/11/2022) (Clinical Trials.gov).

The work relative value estimation assessment in China: an empirical research for common surgical procedures.

Objectives: China's National Health Service Items Standard (NHSIS) establishes a relative value system and plays an important role in pricing. However, there are few empirical evaluations of the objectivity of the NHSIS-estimated relative value. Methods: This paper presents a comparison between physician work relative value units (wRVUs) estimates for 70 common surgical procedures from NHSIS and those from the U.S. Medicare Physician Fee Schedule (MPFS). We defined the ratio of the wRVUs for sample procedures to the benchmark procedure (inguinal hernia repair) as a standardized relative value unit (SRVU), which was used to standardize the data for both schedules. We examined the variances in the ranking and quantification of SRVUs across specialties and procedures, as well as how SRVUs impact procedure reimbursement prices between the two schedules. Results: There was no systematic difference between MHSIS-estimated SRVUs and MPFS-estimated, but the dispersion of MPFS-estimated SRVU was greater than that of MHSIS-estimated, and the discrepancies increased with surgical risk and technical complexity. The discrepancies of SRVUs were significant in cardiothoracic procedures. Additionally, whether SRVUs were based on MPFS or MHSIS, there was a positive association between them and payment prices. However, in terms of the impact of SRVUs on payment pricing, the NHSIS system was lower than the MPFS system. Conclusion: China has made incremental progress in estimating the relative value of healthcare services, but there are shortcomings in valuation methods and their impact on pricing. The modular assessment method should be considered as a component to optimize reform.

Relationship between social support and self-care ability among patients with breast cancer during rehabilitation: The multiple mediating roles of resilience and depression.

AIMS: To identify the multiple mediating effects of resilience and depression between social support and self-care ability among patients with breast cancer during rehabilitation to provide reference for developing and implementing targeted interventions. DESIGN: A cross-sectional study reported according to the STROBE checklist. METHODS: A convenience sample of 320 patients with breast cancer during rehabilitation was recruited from one hospital in China. Data were collected from April to August 2022 using a self-report questionnaire, including the demographic and clinical information, Appraisal of Self-Care Agency Scale-Revised, Multidimensional Scale of Perceived Social Support, Connor-Davidson Resilience Scale-10 item, and Patient Health Questionnaire-9. The mediation analysis was conducted using the SPSS Process macro. RESULTS: Self-care ability was positively associated with social support (ß = .229) and resilience (ß = .290), and negatively associated with depression (ß = -.208). The relationship between social support and self-care ability was mediated by resilience and depression, respectively, and together in serial. The multiple mediating effects accounted for 34.0% of the total effect of social support on self-care ability. CONCLUSION: Our findings identify resilience and depression as multiple mediators between social support and self-care ability and highlight the important roles of social support, resilience and depression in improving self-care ability. RELEVANCE TO CLINICAL PRACTICE: Healthcare providers should pay great attention to the underlying mechanisms of how social support affects patients' self-care ability during breast cancer rehabilitation. Integrated intervention programmes targeted at enhancing social support, building resilience and alleviating depression might be beneficial to the improvement of self-care ability. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. REPORTING METHOD: The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for cross-sectional studies was applied to report the results.

(±)-hypermonanones A-G, seven pairs of monoterpenoid polyprenylated acylphloroglucinol enantiomers from Hypericum monanthemum.

Seven pairs of undescribed monoterpenoid polyprenylated acylphloroglucinol enantiomers [(±)-hypermonanones A-G (1-7)], together with three known analogues, were identified from the whole plant of Hypericum monanthemum Hook. The structures of these compounds were determined by analyses of their UV, HRESIMS, 1D/2D NMR spectroscopic data, and NMR calculations. The absolute configurations of these compounds were assigned by ECD calculations after chiral HPLC separation. Diverse monoterpene moieties were fused at C-3/C-4 of the dearomatized acylphloroglucinol core, which led to 3,4-dihydro-2H-pyran-integrated angular or linear type 6/6/6 tricyclic skeletons in 1-7. Compounds (-)-2 and (+)-2 exhibited significant NO inhibitory activity against LPS induced RAW264.7 cells with the IC50 values of 7.07 ± 1.02 µM and 11.39 ± 0.24 µM, respectively.

METTL5 promotes cell proliferation, invasion, and migration by up-regulating Toll-like receptor 8 expression in colorectal cancer.

BACKGROUND: N6-methyladenosine (m6A) modification represents the predominant alteration found in eukaryotic messenger RNA and plays a crucial role in the progression of various tumors. However, despite its significance, the comprehensive investigation of METTL5, a key m6A methyltransferase, in colorectal cancer (CRC) remains limited. AIM: To investigate the role of METTL5 in CRC. METHODS: We assessed METTL5 expression levels in clinical samples obtained from CRC patients as well as in CRC cell lines. To elucidate the downstream targets of METTL5, we performed RNA-sequencing analysis coupled with correlation analysis, leading us to identify Toll-like receptor 8 (TLR8) as a potential downstream target. In vitro functional assessments of METTL5 and TLR8 were conducted using CCK-8 assays, scratch assays, as well as assays measuring cell migration and invasion. RESULTS: Our findings reveal a pronounced upregulation of METTL5 expression in both CRC cells and tissues, which correlated significantly with an unfavorable prognosis. In vitro experiments unequivocally demonstrated the oncogenic role of METTL5, as evidenced by its promotion of CRC cell proliferation, invasion, and migration. Notably, we identified TLR8 as a downstream target of METTL5, and subsequent down-regulation of TLR8 led to a significant inhibition of CRC cell proliferation, invasion, and tumor growth. CONCLUSION: The heightened expression of METTL5 in CRC is strongly associated with clinicopathological features and a poor prognosis, thereby underscoring its potential utility as a critical marker for facilitating early diagnosis and prognostication in CRC.

Complement system is overactivated in patients with IgA nephropathy after COVID-19.

IgA nephropathy (IgAN), which has been confirmed as a complement mediated autoimmune disease, is also one form of glomerulonephritis associated with COVID-19. Here, we aim to investigate the clinical and immunological characteristics of patients with IgAN after COVID-19. The level of plasma level of C5a (p < 0.001), soluble C5b-9 (p = 0.018), FHR5 (p < 0.001) were all significantly higher in Group CoV (33 patients with renal biopsy-proven IgAN experienced COVID-19) compared with Group non-CoV (44 patients with IgAN without COVID-19), respectively. Compared with Group non-CoV, the intensity of glomerular C4d (p = 0.017) and MAC deposition (p < 0.001) and Gd-IgA1 deposition (p = 0.005) were much stronger in Group CoV. Our finding revealed that for IgAN after COVID-19, mucosal immune responses to SARS-CoV-2 infection may result in the overactivation of systemic and renal local complement system, and increased glomerular deposition of Gd-IgA1, which may lead to renal dysfunction and promote renal progression in IgAN patients.

Effects of exercise interventions on physical, psychological and social outcomes in frail older adults: An overview of systematic reviews.

AIMS: To comprehensively synthesise existing evidence from systematic reviews regarding the effects of exercise interventions on physical, psychological and social outcomes in frail older adults to provide reference for clinical practice. BACKGROUND: Frailty is highly prevalent in older adults and associated with increased adverse health outcomes. Some systematic reviews have assessed the effectiveness of exercise interventions in frail older adults with varied inclusion criteria, methodology quality, types of exercise and outcome measures. DESIGN: An overview of systematic reviews reported following the PRISMA checklist. METHODS: PubMed, Embase, CINAHL, Web of Science and Cochrane database were searched from inception until June 2023 to identify relevant systematic reviews with or without meta-analysis of randomised controlled trails. Two reviewers independently selected articles, extracted data, assessed quality and summarised findings. RESULTS: A total of 17 systematic reviews were included, with methodology quality varying from moderate to critically low. The most frequent types of exercise were multicomponent exercise and resistance-based exercise in community and long-term care facilities, respectively. Exercise interventions had positive effects on most physical outcomes and depression, but inconsistent effects on cognitive function and quality of life. The quality of the evidence for most outcomes was low and very low. CONCLUSIONS: This overview highlights the importance of exercise interventions to improve physical, psychological and social aspects in frail older adults and provides evidence on characteristics of exercise interventions for frailty in various settings. RELEVANCE TO CLINICAL PRACTICE: Multicomponent exercise and resistance-based exercise should be recommended for frail older adults. There is a need of more well-designed research with large sample size and validated definition of frailty. Long-term effects, adherence during and after exercise interventions, adverse events and cost-effectiveness should be emphasised in future studies. TRIAL AND PROTOCOL REGISTRATION: The overview protocol was registered on the International Prospective Register of Systematic reviews (CRD 42021281327). PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. REPORTING METHOD: The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were applied to report the results.

Optimal Glycated Hemoglobin Cutoff for Diagnosis of Diabetes and Prediabetes in Chinese Breast Cancer Women.

Purpose: Glycated hemoglobin (HbA1c) is widely used in diabetes management and now recommended for diagnosis and risk assessment. Our research focused on investigating the optimal cutoff points of HbA1c for diagnosis of diabetes and prediabetes in Chinese breast cancer women, aiming to enhance early detection and tailor treatment strategies. Patients and Methods: This study involved 309 breast cancer women without diabetes history in China. Patients were categorized into groups of newly diagnosed diabetes, prediabetes, and normal glucose tolerance using oral glucose tolerance test (OGTT) according to the 2010 ADA criteria. HbA1c data were collected from all patients. Receiver operating characteristic (ROC) curve analysis was used to assess the effectiveness of the HbA1c screening. Results: Among the 309 breast cancer women without diabetes history, 96 (31.0%) were identified with diabetes and 130 (42.1%) had prediabetes according to OGTT, and the incidence of normal glucose tolerance was only 26.9% (83). ROC curve analysis, using OGTT as a reference, revealed that the area under the curve of 0.903 (P<0.001, 95% CI, 0.867-0.938) for HbA1c alone, indicating high accuracy. The optimal HbA1c cutoff for identifying diabetes was determined to be 6.0%, with a sensitivity of 78.1% and specificity of 86.4%. For prediabetes, the ROC curve for HbA1c alone showed that the area under the ROC curve of 0.703 (P<0.001, 95% CI, 0.632-0.774), with an optimal cutoff of 5.5% (sensitivity of 76.9% and specificity of 51.8%). Conclusion: The prevalence of undiagnosed diabetes is very high in breast cancer women without diabetes history in China. The optimal cutoff points of HbA1c for identifying diabetes and prediabetes are 6.0% and 5.5% in Chinese breast cancer women, respectively.

Histopathological staging and differential diagnosis of marginal zone lymphoma of gastric mucosa-associated lymphoid tissue.

The purpose of this study was to explore the histopathological staging and differential diagnosis of marginal zone lymphoma in gastric mucosa-associated lymphoid tissue (MALT lymphoma). We performed detailed histomorphology and immunohistochemistry investigations as well as genetic testing on endoscopic biopsy and endoscopic mucosal resection specimens from 18 patients with gastric MALT lymphoma. We found that gastric MALT lymphoma typically begins as a small, isolated area outside the lymphoid follicular mantle zone or proliferates in a multifocal, patchy manner, gradually spreads to the interfollicular zone, forming diffuse proliferation, invades the gastric mucosal glands, and infiltrates or proliferates into the center of peripheral reactive lymphoid follicles. Abnormally proliferating lymphocytes invade the surrounding lymphoid follicles, resulting in damage, atrophy, and disappearance of their normal follicles as well as of the gastric mucosa glands, forming diffuse proliferation. Redifferentiation and proliferation lead to the transformation of lymphocytes; that is, MALT transitions into highly invasive lymphoma. Based on our findings in this study, we propose the following five stages in the process of development and progression of gastric MALT lymphoma: the stage of cell proliferation outside the lymphoid follicular mantle zone; the stage of heterogeneous proliferative lymphoepithelial lesion; the stage of reactive lymphoid follicular implantation; the stage of lymphoid follicular clonal proliferation; and the stage of MALT transforming into highly invasive lymphoma. We examined the differential diagnosis of histopathological features at each stage. The clinicopathological staging of gastric MALT lymphoma can help clinicians provide accurate treatment and track malignant cell transformation, thus playing a significant role in controlling its development and progression.

The discovery of an anti-Candida xanthone with selective inhibition of Candida albicans GAPDH.

OBJECTIVES: This study aimed to discover novel antifungals targeting Candida albicans glyceraldehyde-3-phosphate dehydrogenase (CaGAPDH), have an insight into inhibitory mode, and provide evidence supporting CaGAPDH as a target for new antifungals. METHODS: Virtual screening was utilized to discover inhibitors of CaGAPDH. The inhibitory effect on cellular GAPDH was evaluated by determining the levels of ATP, NAD, NADH, etc., as well as examining GAPDH mRNA and protein expression. The role of GAPDH inhibition in C. albicans was supported by drug affinity responsive target stability and overexpression experiments. The mechanism of CaGAPDH inhibition was elucidated by Michaelis-Menten enzyme kinetics and site-specific mutagenesis based on docking. Chemical synthesis was used to produce an improved candidate. Different sources of GAPDH were used to evaluate inhibitory selectivity across species. In vitro and in vivo antifungal tests, along with anti-biofilm activity, were carried out to evaluate antifungal potential of GAPDH inhibitors. RESULTS: A natural xanthone was identified as the first competitive inhibitor of CaGAPDH. It demonstrated in vitro anti-C. albicans potential but also caused hemolysis. XP-W, a synthetic side-chain-optimized xanthone, demonstrated a better safety profile, exhibiting a 50-fold selectivity for CaGAPDH over human GAPDH. XP-W also exhibited potent anti-biofilm activity and displayed broad-spectrum anti-Candida activities in vitro and in vivo, including multi-azole-resistant C. albicans. CONCLUSIONS: These results demonstrate for the first time that CaGAPDH is a valuable target for antifungal drug discovery, and XP-W provides a promising lead.

The contribution of periaqueductal gray in the regulation of physiological and pathological behaviors.

Periaqueductal gray (PAG), an integration center for neuronal signals, is located in the midbrain and regulates multiple physiological and pathological behaviors, including pain, defensive and aggressive behaviors, anxiety and depression, cardiovascular response, respiration, and sleep-wake behaviors. Due to the different neuroanatomical connections and functional characteristics of the four functional columns of PAG, different subregions of PAG synergistically regulate various instinctual behaviors. In the current review, we summarized the role and possible neurobiological mechanism of different subregions of PAG in the regulation of pain, defensive and aggressive behaviors, anxiety, and depression from the perspective of the up-down neuronal circuits of PAG. Furthermore, we proposed the potential clinical applications of PAG. Knowledge of these aspects will give us a better understanding of the key role of PAG in physiological and pathological behaviors and provide directions for future clinical treatments.

A case of diffuse large B-cell lymphoma with decompensated alcohol-related liver cirrhosis treated successfully by chemoimmunotherapy.

Key Clinical Message: This report describes a case of diffuse large B-cell lymphoma with MYD88 L265P and KM2DT mutation and decompensated alcohol-related liver cirrhosis. And the treatment is successful in this patient, who had multiple complications and poor prognostic factors. Abstract: This report describes a case of diffuse large B-cell lymphoma with MYD88 L265P and KM2DT mutation and decompensated alcohol-related liver cirrhosis. The lymphoma showed a complete response with no MYD88 L265P mutation after four courses of combination chemotherapy. Lymphoma is one of the most common malignant tumors, but cases of DLBCL with cirrhosis are much rarer especially with alcohol-related cirrhosis. And we reviewed the relevant mechanisms. Although we did not find a definite association between the pathogenesis of the patient's alcohol-related cirrhosis and that of diffuse large B-cell lymphoma, the treatment is successful in this patient, who had multiple complications and poor prognostic factors.