Morinda officinalis oligosaccharides modulate the default-mode network homogeneity in major depressive disorder at rest.

BACKGROUND: While prior studies have explored the efficacy of Morinda officinalis oligosaccharides (MOs) as a treatment for patients with major depressive disorder (MDD), the mechanistic basis for the effects of MOs on brain function or the default-mode network (DMN) has yet to be characterized. The objective of this was to examine the effects of MOs treatment on functional connectivity in different regions of the DMN. METHODS: In total, 27 MDD patients and 29 healthy control subjects (HCs) underwent resting-state functional magnetic resonance imaging. The patients were then treated with MOs for 8 weeks, and scanning was performed at baseline and the end of the 8-week treatment period. Changes in DMN homogeneity associated with MOs treatment were assessed using network homogeneity (NH) analyses of the imaging data, and pattern classification approaches were employed to determine whether abnormal baseline NH deficits could differentiate between MDD patients and controls. The ability of NH abnormalities to predict patient responses to MOs treatment was also evaluated. RESULTS: Relative to HCs, patients exhibited a baseline reduction in NH values in the right precuneus (PCu). At the end of the 8-week treatment period, the MDD patients showed reduced and increased NH values in the right PCu and left superior medial frontal gyrus (SMFG), respectively. Compared to these patients at baseline, the 8-week MOs treatment was associated with reduced NH values in the right angular gyrus and increased NH values in the left middle temporal gyrus and the right PCu. Support vector machine (SVM) analyses revealed that NH abnormalities in the right PCu and left SMFG were the most accurate (87.50%) for differentiating between MDD patients and HCs. CONCLUSION: These results indicated that MOs treatment could alter default-mode NH in patients with MDD. The results provide a foundation for elucidation of the effects of MOs on brain function and suggest that the distinctive NH patterns observed in this study may be useful as imaging biomarkers for distinguishing between patients with MDD and healthy subjects.

Latilactobacillus sakei QC9 alleviates hyperglycaemia in high-fat diet and streptozotocin-induced type 2 diabetes mellitus mice via the microbiota-gut-liver axis.

Probiotics have been considered a promising option for mitigating the progression of type 2 diabetes mellitus (T2DM). Here, Latilactobacillus sakei QC9 (L. sakei QC9) with a hypoglycemic effect was screened out from 30 food-derived strains through α-glucosidase and α-amylase activity inhibition tests in vitro and a 4-week in vivo preliminary animal experiment. To further understand its alleviating effect on long-term hyperglycaemia occurring in T2DM, we conducted an experiment that lasted for 8 weeks. The results showed that taking L. sakei QC9 can regulate glucose and lipid metabolism while improving the antioxidant capacity and alleviating chronic inflammation. In addition, our results demonstrated that L. sakei QC9 may mediate the microbiota-gut-liver axis by regulating the composition of intestinal flora (increasing the abundance of butyrate-producing bacteria) and increasing the content of short-chain fatty acids (especially butyrate), affecting the PI3K/Akt signalling pathway in the liver, thereby achieving the purpose of alleviating the development of T2DM. In summary, our work is the first to prove the long-term hypoglycemic effect of L. sakei in high-fat diet (HFD) and streptozotocin (STZ)-induced T2DM mice and supports the possibility of L. sakei QC9 being used as a new treatment for alleviating T2DM.

Exposure of women undergoing In-Vitro Fertilization to per-and polyfluoroalkyl substances: Evidence on negative effects on Fertilization and high-quality embryos.

In April 2023, the World Health Organization (WHO) reported that 17.5% of the global adult population experience infertility. What may be the contribution of per-and polyfluoroalkyl (PFAS) to this global public health problem? This study explored the associations between in vitro fertilization (IVF) outcomes and plasma concentrations of individual PFAS and PFAS mixtures in women undergoing in vitro fertilization and embryo transfer (IVF-ET) and how these exposures might affect IVF outcomes. We analyzed 8 PFASs in plasma samples from women (N=259) who underwent IVF treatment. In multivariable generalized linear mixed models, there were statistically significant associations of higher plasma concentrations of PFNA with reduced numbers of total retrieved oocytes [12.486 (95%CI:-0.446,25.418), p trend=0.017], 2PN zygotes [6.467(95%CI:-2.034,14.968), p trend=0.007], and cleavage embryos [6.039(95%CI:-2.162,14.240), p trend=0.008]. Similarly, there was a continuous decline in the numbers of retrieved 2PN zygotes and cleavage embryos with increasing concentration of PFOS [6.467(95%CI:-2.034,14.968), p trend=0.009 and 6.039(95%CI:-2.162,14.240), p trend=0.031,respectively] and a negative association between PFHxS concentrations and clinical pregnancy during the initial cycles of frozen ET [0.525(95%CI:0.410,0.640), p trend=0.021]. To investigate the joint effect of PFAS mixtures, a confounder-adjusted BKMR model analysis showed inverse relationship between PFAS mixtures and the number of high-quality embryos, 2PN zygotes and cleavage embryos, to which the greatest contributors to the mixture effect are PFDeA and PFBS, respectively. It demonstrated that PFAS exposure might exert negative effects on oocyte yield, fertilization and high-quality embryo in women undergoing IVF. These findings suggest that exposure to PFAS may increase the risk of female infertility and further studies are needed to uncover the potential mechanisms underlying the reproductive effects associated with PFAS.

p110CUX1 promotes acute myeloid leukemia progression via regulating pyridoxal phosphatase expression and activating PI3K/AKT/mTOR signaling pathway.

As an evolutionarily conserved transcription factor, Cut-like homeobox 1 (CUX1) plays crucial roles in embryonic and nervous system development, cell differentiation, and DNA damage repair. One of its major isoforms, p110CUX1, exhibits stable DNA binding capabilities and contributes to the regulation of cell cycle progression, proliferation, migration, and invasion. While p110CUX1 has been implicated in the progression of various malignant tumors, its involvement in acute myeloid leukemia (AML) remains uncertain. This study aims to elucidate the role of p110CUX1 in AML. Our findings reveal heightened expression levels of both p110CUX1 and pyridoxal phosphatase (PDXP) in AML cell lines. Overexpression of p110CUX1 promotes AML cell proliferation while inhibiting apoptosis and differentiation, whereas knockdown of PDXP yields contrasting effects. Mechanistically, p110CUX1 appears to facilitate AML development by upregulating PDXP expression and activating the PI3K/AKT/mTOR signaling pathway. Animal experimental corroborate the pro-AML effect of p110CUX1. These results provide experimental evidence supporting the involvement of the p110CUX1-PDXP-PI3K/AKT/mTOR axis in AML progression. Hence, targeting p110CUX1 may hold promise as a therapeutic strategy for AML.

PI3K PROTAC overcomes the lapatinib resistance in PIK3CA-mutant HER2 positive breast cancer.

Although anti-HER2 therapy has made significant strides in reducing metastasis and relapse in HER2-positive breast cancer, resistance to agents like trastuzumab, pertuzumab, and lapatinib frequently develops in patients undergoing treatment. Previous studies suggest that the hyperactivation of the PI3K-AKT signaling pathway by PIK3CA/PTEN gene mutations is implicated in HER2 resistance. In this study, we introduce a novel PI3K-p110α Proteolysis TAargeting Chimera (PROTAC) that effectively inhibits the proliferation of breast cancer cells by degrading PI3K-p110α. When tested in two lapatinib-resistant cell lines, JIMT1 and MDA-MB-453, both of which harbor PIK3CA mutations, the PI3K PROTAC notably reduced cell proliferation and induced G1 phase cell cycle arrest. Importantly, even at very low concentrations, PI3K PROTAC restored sensitivity to lapatinib. Furthermore, the efficacy of PI3K PROTAC surpassed that of Alpelisib, a selective PI3K-p110α kinase inhibitor in clinic. The superior performance of PI3K PROTAC was also confirmed in lapatinib-resistant breast cancer xenograft tumors and patient-derived breast cancer organoids (PDOs). In conclusion, this study reveals that the novel PI3K PROTAC we synthesized could serve as an effective agent to overcome lapatinib resistance.

Preparation and Mechanism Analysis of High-Performance Humidity Sensor Based on Eu-Doped TiO2.

TiO2 is a typical semiconductor material, and it has attracted much attention in the field of humidity sensors. Doping is an efficient way to enhance the humidity response of TiO2. Eu-doped TiO2 material was investigated in both theoretical simulations and experiments. In a simulation based on density functional theory, a doped Eu atom can increase the performance of humidity sensors by producing more oxygen vacancies than undoped TiO2. In these experiments, Eu-doped TiO2 nanorods were prepared by hydrothermal synthesis, and the results also confirm the theoretical prediction. When the doping mole ratio is 5 mol%, the response of the humidity sensor reaches 23,997.0, the wet hysteresis is 2.3% and the response/recovery time is 3/13.1 s. This study not only improves the basis for preparation of high-performance TiO2 humidity sensors, but also fills the research gap on rare earth Eu-doped TiO2 as a humidity-sensitive material.

[Prospective,multi-center,and large-scale hospital centralized monitoring of clinical safety of Reduning Injection in 100249 children cases].

This study utilized a prospective, large-sample, multi-center, and registered key specialty approach of hospitals to monitor the application of Reduning Injection. A total of 100 249 adolescent patients aged 14 years and below who received Reduning Injection were monitored, resulting in 83 cases of adverse events, with 76 of them being classified as adverse drug reaction(ADR). The calculated incidence rate of ADR for Reduning Injection was 0.076%, indicating a very rare ADR. The main symptoms of ADR were pruritus, diarrhea, abdominal pain, vomiting, high fever, dyspnea, convulsion, and chills. All ADR cases were reported for the first time, including three new ADR cases and 73 known ADR cases. The categories of ADR was general ADR. All ADR was mild in severity. There were more males than females in ADR patients. One patient had a history of ADR, and the drug causing ADR was buprofen. The largest number of ADR cases occurred when the dosage of Reduning injection was 5-10 mL. The dropping speed was 30 drops or less per min, and the solvent type was 5% glucose injection. The most common manifestation of ADR patients was pruritus, followed by diarrhea, abdominal pain, vomiting, high fever, dyspnea, convulsions, and chills. 72 patients(94.74% of ADR patients) discontinued the drug, and three patients(3.95% of ADR patients) were given oxygen inhalation. 47 cases(61.84% of ADR patients) were treated with medication, of which dexamethasone was the most used(24 cases, 46.15% of ADR patients). 76 ADR patients were cured or improved. ADRs are more likely to occur when diagnosed with acute bronchitis by western medicine and cough by traditional Chinese medicine(TCM), TCM syndrome type is wind heat syndrome, and the combination medicine is ambroxol hydrochloride and bromhexine hydrochloride injection, ascorbic acid/vitamin C injection. This result provides an evidence-based safety basis for active pharmacovigilance of Reduning Injection in adolescents aged 14 years and below.

Effectiveness of Psychobiotic Bifidobacterium breve BB05 in Managing Psychosomatic Diarrhea in College Students by Regulating Gut Microbiota: A Randomized, Double-Blind, Placebo-Controlled Trial.

Diarrhea of college students (DCS) is a prevalent issue among college students, affecting their daily lives and academic performance. This study aims to explore the potential effect of Bifidobacterium breve BB05 supplements on the DCS. Initially, fifty healthy and fifty diarrheal students were recruited in the observational experiment and allocated into control and diarrhea groups, respectively. Subsequently, one hundred diarrheal students were newly recruited in the intervention experiment and randomly allocated into placebo and probiotic groups, both treated for 2 weeks. Questionnaires (BSS, HAMA-14, and HDRS-17) were performed to assess the students' diarrheal states and mental health at baseline and post-treatment. Fecal samples underwent 16S rRNA sequencing and Enzyme-Linked Immunosorbent Assay to evaluate gut microbiota and fecal metabolite alternations. Results indicated that B. breve BB05 supplementation significantly enriched (p < 0.05) the reduced gut microbial diversity caused by diarrhea. Diarrhea resulted in notable alterations in gut microbiota composition, as exhibited by elevated Collinsella and Streptococcus, alongside substantially decreased Bifidobacterium, Bacteroides, and Prevotella, while B. breve BB05 supplementation partially restored the compromised gut microbiota at both the phylum and genus levels, particularly by increasing Bifidobacterium and Roseburia (p < 0.05). Importantly, questionnaire results suggested that B. breve BB05 administration achieved superior efficacy in relieving diarrhea symptoms and the associated anxiety and depression in college students. An increased fecal concentration of 5-hydroxytryptamine (5-HT) was also observed in the probiotic group, while Acetylcholine (ACH), Epinephrine (EPI), and Noradrenaline/Norepinephrine (NANE) reduced, revealing the potential of B. breve BB05 in alleviating anxiety and depression via modulating the microbiota-gut-brain axis. Furthermore, correlation analysis suggested that the altered microbiota and fecal neurotransmitters were closely associated with the mental symptoms. These results endorse B. breve BB05 intervention as a promising and innovative approach to alleviate both diarrhea and mental health conditions among college students.

ISIS 449884 Injection Add-On to Metformin in Patients with Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled, Phase II Clinical Study.

INTRODUCTION: ISIS 449884, a 2'-O-methoxyethyl antisense oligonucleotide that targets the glucagon receptor (GCGR), has demonstrated an ability to reduce hepatic glucose output and lower the blood glucose level. The primary objective of this study was to investigate the safety and efficacy of ISIS 449884 as an add-on to metformin in a population of Chinese patients with type 2 diabetes mellitus (T2DM). METHOD: This was a multicenter, placebo-controlled (2:1), randomized, double-blind, parallel-enrollment, multiple-dose phase II study in Chinese patients with T2DM. A total of 90 patients who were uncontrolled by stable metformin monotherapy were randomized into three cohorts. Thirty subjects were enrolled in each cohort and received injections of ISIS 449884 (50 mg or 60 mg weekly or 100 mg every other week) or a corresponding volume of placebo (0.25 mL and 0.3 mL weekly or 0.5 mL every other week) subcutaneously in a 2:1 ratio for 16 weeks. RESULTS: The primary efficacy endpoint was analyzed in 88 subjects (ISIS 449884, n = 59; placebo, n = 29). The corrected LS mean change from baseline in glycated hemoglobin (HbA1c) at week 17 in the pooled ISIS 449884 treatment group was - 1.31% (95% CI - 1.66%, - 0.96%), and that in the pooled placebo group was 0.15% (95% CI - 0.37%, 0.66%). The LS mean difference between the two groups was - 1.46% (95% CI - 1.92%, - 1.00%, P < 0.001). Treatment-emergent adverse events (TEAEs) occurred in 53/60 subjects (88.3%) and 25/30 subjects (83.3%) in the pooled ISIS 449884 treatment group and the pooled placebo group, respectively, with similar incidences. Drug-related TEAEs occurred in 41/60 subjects (68.3%) and 9/30 subjects (30.0%), respectively. TEAEs of grade 3 or higher occurred in 5/60 (8.3%) subjects and 2/30 (6.7%) subjects, respectively, and none of them were drug related. CONCLUSIONS: The ISIS 449884 injection add-on to metformin significantly reduced HbA1c in patients with T2DM uncontrolled by stable metformin monotherapy and showed an acceptable benefit/risk profile. CLINICAL TRIAL REGISTRATION: www.chinadrugtrials.org.cn , CTR20191096.

Whole-brain radiation therapy plus simultaneous integrated boost for brain metastases from breast cancers.

Background: The effect of whole-brain radiation therapy (WBRT) plus simultaneous integrated boost (SIB) in brain metastasis from breast cancers has not been demonstrated. Method: In this single-center retrospective study, we reviewed consecutive breast cancer patients who developed brain metastasis and were treated with hypofractionated radiation therapy plus WBRT using intensity-modulated radiation therapy (IMRT)-SIB approaches. We analyzed clinical outcomes, prognostic factors and patterns of treatment failure. Result: A total of 27 patients were eligible for analysis. Four (14.8%) patients achieved clinical complete response and 14 (51.9%) had partial response of brain lesions. The other nine patients were not evaluated for brain tumor response. The median brain progression-free survival was 8.60 (95% CI [6.43-13.33]) months and the median overall survival was 16.8 (95% CI [13.3-27.7]) months. Three patients had in-field failure, five had out-field failure and two had in-field and out-field failure. Conclusion: WBRT plus SIB led to improved tumor control and clinical outcome in breast cancer patients with brain metastasis.

Digital Health Interventions for Chronic Wound Management: A Systematic Review and Meta-Analysis.

BACKGROUND: Digital health interventions (DHIs) have shown promising results for the management of chronic wounds. However, its effectiveness compared to usual care and whether variability in the type of intervention affects wound outcomes are unclear. OBJECTIVE: The main objective was to determine the effectiveness of DHIs on wound healing outcomes in adult patients with chronic wounds. The secondary objectives were to assess if there was any variation in wound healing outcomes across the various types of DHIs. METHODS: In total, 9 databases were searched for the literature up to August 1, 2023. Randomized controlled trials (RCTs), cohort studies, and quasi-experimental studies comparing the efficacy of DHIs with controls in improving wound outcomes in adult patients with chronic wounds were included. Study selection, data extraction, and risk of bias assessment were conducted independently by 2 reviewers. We assessed the quality of each RCT, cohort study, and quasi-experimental study separately using the Cochrane risk of bias tool, ROBINS-I, and the Joanna Briggs Institute Critical Appraisal tools checklists. Relative risks (RRs) and 95% CIs were pooled using the random effects model, and heterogeneity was assessed by the I2 statistic. Subgroup analysis and sensitivity analysis were also performed. RESULTS: A total of 25 studies with 8125 patients were included in this systematic review, while only 20 studies with 6535 patients were included in the meta-analysis. Efficacy outcomes in RCTs showed no significant differences between the DHIs and control groups in terms of wound healing (RR 1.02, 95% CI 0.93-1.12; P=.67) and all-cause mortality around 1 year (RR 1.08, 95% CI 0.55-2.12; P=.83). Compared with the control group, the use of DHIs was associated with significant changes in adverse events (RR 0.44, 95% CI 0.22-0.89; P=.02). Subgroup analysis suggested a positive effect of the digital platforms in improving wound healing (RR 2.19, 95% CI 1.35-3.56; P=.002). Although meta-analysis was not possible in terms of wound size, cost analysis, patient satisfaction, and wound reporting rates, most studies still demonstrated that DHIs were not inferior to usual care in managing chronic wounds. CONCLUSIONS: The findings of our study demonstrate the viability of adopting DHIs to manage chronic wounds. However, more prominent, high-quality RCTs are needed to strengthen the evidence, and more detailed clinical efficacy research is required. TRIAL REGISTRATION: PROSPERO CRD42023392415; https://tinyurl.com/4ybz6bs9.

Deep graph contrastive learning model for drug-drug interaction prediction.

Drug-drug interaction (DDI) is the combined effects of multiple drugs taken together, which can either enhance or reduce each other's efficacy. Thus, drug interaction analysis plays an important role in improving treatment effectiveness and patient safety. It has become a new challenge to use computational methods to accelerate drug interaction time and reduce its cost-effectiveness. The existing methods often do not fully explore the relationship between the structural information and the functional information of drug molecules, resulting in low prediction accuracy for drug interactions, poor generalization, and other issues. In this paper, we propose a novel method, which is a deep graph contrastive learning model for drug-drug interaction prediction (DeepGCL for brevity). DeepGCL incorporates a contrastive learning component to enhance the consistency of information between different views (molecular structure and interaction network), which means that the DeepGCL model predicts drug interactions by integrating molecular structure features and interaction network topology features. Experimental results show that DeepGCL achieves better performance than other methods in all datasets. Moreover, we conducted many experiments to analyze the necessity of each component of the model and the robustness of the model, which also showed promising results. The source code of DeepGCL is freely available at https://github.com/jzysj/DeepGCL.

Can a shift in dominant species of Microcystis alter growth and reproduction of waterfleas?

The bloom-forming species Microcystis wesenbergii and M. aeruginosa occur in many lakes globally, and may exhibit alternating blooms both spatially and temporally. As environmental changes increase, cyanobacteria bloom in more and more lakes and are often dominated by M. wesenbergii. The adverse impact of M. aeruginosa on co-existing organisms including zooplanktonic species has been well-studied, whereas studies of M. wesenbergii are limited. To compare effects of these two species on zooplankton, we explored effects of exudates from different strains of microcystin-producing M. aeruginosa (Ma905 and Ma526) and non-microcystin-producing M. wesenbergii (Mw908 and Mw929), on reproduction by the model zooplankter Daphnia magna in both chronic and acute exposure experiments. Specifically, we tested physiological, biochemical, molecular and transcriptomic characteristics of D. magna exposed to Microcystis exudates. We observed that body length and egg and offspring number of the daphnid increased in all treatments. Among the four strains tested, Ma526 enhanced the size of the first brood, as well as total egg and offspring number. Microcystis exudates stimulated expression of specific genes that induced ecdysone, juvenile hormone, triacylglycerol and vitellogenin biosynthesis, which, in turn, enhanced egg and offspring production of D. magna. Even though all strains of Microcystis affected growth and reproduction, large numbers of downregulated genes involving many essential pathways indicated that the Ma905 strain might contemporaneously induce damage in D. magna. Our study highlights the necessity of including M. wesenbergii into the ecological risk evaluation of cyanobacteria blooms, and emphasizes that consequences to zooplankton may not be clear-cut when assessments are based upon production of microcystins alone.

Multifunctional pH-responsive hydrogel dressings based on carboxymethyl chitosan: Synthesis, characterization fostering the wound healing.

Antibiotic abuse is increasing the present rate of drug-resistant bacterial wound infections, producing a significant healthcare burden globally. Herein, we prepared a pH-responsive CMCS/PVP/TA (CPT) multifunctional hydrogel dressing by embedding the natural plant extract TA as a nonantibiotic and cross-linking agent in carboxymethyl chitosan (CMCS) and polyvinylpyrrolidone (PVP) to prompt wound healing. The CPT hydrogel demonstrated excellent self-healing, self-adaptive, and adhesion properties to match different wound requirements. Importantly, this hydrogel showed pH sensitivity and exhibited good activity against resistant bacteria and antioxidant activity by releasing TA in case of bacterial infection (alkaline). Furthermore, the CPT hydrogel exhibited coagulant ability and could rapidly stop bleeding within 30 s. The biocompatible hydrogel effectively accelerated wound healing in a full-thickness skin defect model by thickening granulation tissue, increasing collagen deposition, vascular proliferation, and M2-type macrophage polarization. In conclusion, this study demonstrates that multifunctional CPT hydrogel offers a candidate material with potential applications for infected skin wound healing.

Disambiguity and Alignment: An Effective Multi-Modal Alignment Method for Cross-Modal Recipe Retrieval.

As a prominent topic in food computing, cross-modal recipe retrieval has garnered substantial attention. However, the semantic alignment across food images and recipes cannot be further enhanced due to the lack of intra-modal alignment in existing solutions. Additionally, a critical issue named food image ambiguity is overlooked, which disrupts the convergence of models. To these ends, we propose a novel Multi-Modal Alignment Method for Cross-Modal Recipe Retrieval (MMACMR). To consider inter-modal and intra-modal alignment together, this method measures the ambiguous food image similarity under the guidance of their corresponding recipes. Additionally, we enhance recipe semantic representation learning by involving a cross-attention module between ingredients and instructions, which is effective in supporting food image similarity measurement. We conduct experiments on the challenging public dataset Recipe1M; as a result, our method outperforms several state-of-the-art methods in commonly used evaluation criteria.

Efficacy of electrical stimulation for post-stroke motor dysfunction: A protocol for systematic review and network meta-analysis.

OBJECTIVE: This study aims to analyze the efficacy and safety of different electrical stimulation treatments for post-stroke motor dysfunction, and to quantitatively analyze the advantages between them and their possible benefits for patients. METHODS: We will systematically search seven databases. All of them will be retrieved from inception to 15, April 2024. Two reviewers will evaluation the risk of bias in all included studies with the version 2 of the Cochrane risk-of-bias assessment tool. Data synthesis will be performed using a random-effects model of network meta-analysis to compare the efficacy and safety of different electrical stimulation therapies. The surface under the cumulative ranking curve was used to indicate the possibility of the pros and cons of the intervention. The strength of evidence will be assessed by the Grading of Recommendations, Assessment, Development, and Evaluation framework. DISCUSSION: This study will provide evidence that electrical stimulation therapy can effectively improve motor function in stroke patients and will also provide some valuable references for clinical decision-making and treatment guidelines. TRIAL REGISTRATION: PROSPERO registration number: CRD42023459102.

Apolipoprotein D facilitates rabies virus propagation by interacting with G protein and upregulating cholesterol.

Rabies virus (RABV) causes a fatal neurological disease, consisting of unsegmented negative-strand RNA, which encodes five structural proteins (3'-N-P-M-G-L-5'). Apolipoprotein D (ApoD), a lipocalin, is upregulated in the nervous system after injury or pathological changes. Few studies have focused on the role of ApoD during virus infection so far. This study demonstrated that ApoD is upregulated in the mouse brain (in vivo) and C8-D1A cells (in vitro) after RABV infection. By upregulating ApoD expression in C8-D1A cells, we found that ApoD facilitated RABV replication. Additionally, Co-immunoprecipitation demonstrated that ApoD interacted with RABV glycoprotein (G protein). The interaction could promote RABV replication by upregulating the cholesterol level. These findings revealed a novel role of ApoD in promoting RABV replication and provided a potential therapeutic target for rabies.

Qualitative and Psychometric Evaluation of 29-Item Patient-Reported Outcomes Measurement Information System® to Assess General Health-Related Quality of Life in Patients With Moderately to Severely Active Inflammatory Bowel Disease.

OBJECTIVES: To evaluate content validity and psychometric properties of the 29-item Patient-Reported Outcomes Measurement Information System (PROMIS-29) to determine its suitability in inflammatory bowel disease (IBD) clinical trials. METHODS: Content validity of PROMIS-29 was evaluated using qualitative interviews, including concept elicitation and cognitive debriefing, among patients living with Crohn's disease (Crohn's disease n = 20) or ulcerative colitis (UC, n = 19). PROMIS-29 validity, reliability, and responsiveness were assessed using data from phase II clinical trials of Crohn's disease (N = 360) and UC (N = 518). RESULTS: Common (≥74%) symptoms reported in qualitative interviews were increased stool frequency, fatigue, abdominal pain/cramping, blood/mucus in stool, bowel urgency, and diarrhea. Disease impact aligned with PROMIS-29 content (depression, anxiety, physical function, pain interference, fatigue, sleep disturbance, and ability to participate in social roles/activities). Cognitive debriefing indicated that PROMIS-29 instructions were easily understood, items were relevant, and the recall period was appropriate. Psychometric evaluations demonstrated that PROMIS-29 scores indicating worse symptoms/functioning were associated with lower health-related quality of life and greater disease activity and severity. PROMIS-29 domain scores correlated (rs ≥ 0.40) with IBD Questionnaire domains and EuroQol-5-Dimension-5-Level dimensions measuring similar concepts. Test-retest reliability among patients with stable disease was moderate-to-excellent (0.64-0.94) for nearly all domains in all studies. PROMIS-29 was responsive to change in disease status from baseline to week 12. Thresholds for clinically meaningful improvement ranged from ≥3 to ≥8, depending on domain. CONCLUSIONS: PROMIS-29 is valid, reliable, and responsive for assessing general health-related quality of life and treatment response in IBD clinical trials.

Peceleganan Spray for the Treatment of Skin Wound Infections: A Randomized Clinical Trial.

Importance: Peceleganan spray is a novel topical antimicrobial agent targeted for the treatment of skin wound infections. However, its efficacy and safety remain unclear. Objective: To assess the safety and efficacy of peceleganan spray for the treatment of wound infections. Design, Setting, and Participants: This multicenter, open-label, phase 3 randomized clinical trial recruited and followed up 570 adult patients diagnosed with secondary open wound infections from 37 hospitals in China from August 23, 2021, to July 16, 2022. Interventions: Patients were randomized to 2 groups with a 2:1 allocation. One group received treatment with 2% peceleganan spray (n = 381) and the other with 1% silver sulfadiazine (SSD) cream (n = 189). Main Outcomes and Measures: The primary efficacy outcome was the clinical efficacy rate (the number of patients fulfilling the criteria for efficacy of the number of patients receiving the treatment) on the first day following the end of treatment (day 8). The secondary outcomes included the clinical efficacy rate on day 5 and the bacterial clearance rate (cases achieving negative bacteria cultures after treatment of all cases with positive bacteria cultures before treatment) on days 5 and 8. The safety outcomes included patients' vital signs, physical examination results, electrocardiographic findings, blood test results, and adverse reactions. Results: Among the 570 patients randomized to 1 of the 2 groups, 375 (98.4%) in the 2% peceleganan treatment group and 183 (96.8%) in the 1% SSD control group completed the trial (n = 558). Of these, 361 (64.7%) were men, and the mean (SD) age was 48.6 (15.3) years. The demographic characteristics were similar between groups. On day 8, clinical efficacy was achieved by 339 patients (90.4%) in the treatment group and 144 (78.7%) in the control group (P < .001). On day 5, clinical efficacy was achieved by 222 patients (59.2%) in the treatment group and 90 (49.2%) in the control group (P = .03). On day 8, bacterial clearance was achieved by 80 of 334 patients (24.0%) in the treatment group and in 75 of 163 (46.0%) in the control group (P < .001). On day 5, bacterial clearance was achieved by 55 of 334 patients (16.5%) in the treatment group and 50 of 163 (30.7%) in the control group (P < .001). The adverse events related to the application of peceleganan spray and SSD cream were similar. Conclusions and Relevance: This randomized clinical trial found that peceleganan spray is a safe topical antimicrobial agent with a satisfactory clinical efficacy rate for the treatment of skin wound infections, while the effectiveness of bacterial clearance remains uncertain. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2100047202.

LW-1 induced resistance to TMV in tobacco was mediated by nitric oxide and salicylic acid pathway.

The objective of this study was to investigate the mechanism underlying LW-1-induced resistance to TMV in wild-type and salicylic acid (SA)-deficient NahG transgenic tobacco plants. Our findings revealed that LW-1 failed to induce antivirus infection activity and increase SA content in NahG tobacco, indicating the crucial role of SA in these processes. Meanwhile, LW-1 triggered defense-related early-signaling nitric oxide (NO) generation, as evidenced by the emergence of NO fluorescence in both types of tobacco upon treatment with LW-1, however, NO fluorescence was stronger in NahG compared to wild-type tobacco. Notably, both of them were eliminated by the NO scavenger cPTIO, which also reversed LW-1-induced antivirus activity and the increase of SA content, suggesting that NO participates in LW-1-induced resistance to TMV, and may act upstream of the SA pathway. Defense-related enzymes and genes were detected in tobacco with or without TMV inoculation, and the results showed that LW-1 regulated both enzyme activity (ß-1,3-glucanase [GLU], catalase [CAT] and phenylalanine ammonia-lyase [PAL]) and gene expression (PR1, PAL, WYKY4) through NO signaling in both SA-dependent and SA-independent pathways.