The tuber-specific StbHLH93 gene regulates proplastid-to-amyloplast development during stolon swelling in potato.

In potato, stolon swelling is a complex and highly regulated process, and much more work is needed to fully understand the underlying mechanisms. We identified a novel tuber-specific basic helix-loop-helix (bHLH) transcription factor, StbHLH93, based on the high-resolution transcriptome of potato tuber development. StbHLH93 is predominantly expressed in the subapical and perimedullary region of the stolon and developing tubers. Knockdown of StbHLH93 significantly decreased tuber number and size, resulting from suppression of stolon swelling. Furthermore, we found that StbHLH93 directly binds to the plastid protein import system gene TIC56 promoter, activates its expression, and is involved in proplastid-to-amyloplast development during the stolon-to-tuber transition. Knockdown of the target TIC56 gene resulted in similarly problematic amyloplast biogenesis and tuberization. Taken together, StbHLH93 functions in the differentiation of proplastids to regulate stolon swelling. This study highlights the critical role of proplastid-to-amyloplast interconversion during potato tuberization.

Anlotinib plus Sintilimab achieved in an antitumor effect of complete remission in a patient with advanced hepatocellular carcinoma: a case report.

Systemic therapies-based combination treatments have been developed rapidly in patients with advanced hepatocellular carcinoma (HCC). However, there are still a few patients not applicable to any recommended therapies, making it considerable to try new therapeutic options. Among them, anlotinib, a new oral tyrosine kinase inhibitor, is being widely used for many advanced malignancies. We present the first case of the antitumor effect of complete remission by anlotinib combined with an anti-programmed cell death protein 1 antibody, sintilimab, in a patient with advanced HCC. In April 2020, a 51-year-old male patient was diagnosed with large HCC and underwent hepatectomy with R0 resection. Two months later, he was admitted to our hospital because of a tumor relapse with multiple liver and lung metastases. After the failure of comprehensive treatment containing sorafenib, camrelizumab and transhepatic arterial chemotherapy and embolization, 2 months after tumor relapse, the patient started to receive anlotinib and sintilimab. The multiple tumor nodules were remarkable repressed both in the liver and lung. Six months after anlotinib plus sintilimab treatment, there were no residual tumors, and the alpha-fetoprotein level was decreased from 2310.9 mg/L to normal. Also, the patient continued to receive anlotinib to date. In subsequent follow-up visits until now, there was no sign of recurrence found on imaging. Anlotinib is a promising alternative for patients insensitive to the first-line targeted drugs. More clinical studies should be conducted to further broaden the clinical indications of anlotinib and immunotherapy in patients with HCC.

Arterial stiffness progression in metabolic dysfunction-associated fatty liver disease subtypes: A prospective cohort study.

BACKGROUND AND AIMS: We aimed to investigate the correlation and to explore which MAFLD subtypes have the greatest influence on progression of arterial stiffness risk. METHODS AND RESULTS: Using data from a health examination-based cohort, a total of 12,129 participants who underwent two repeated health examinations that included brachial-ankle pulse wave velocity (baPWV) from 2012 to 2020 were enrolled. Participants were separated into non-MAFLD, overweight/obese (OW-MAFLD), lean/normal weight (lean-MAFLD) and diabetes (DM-MAFLD) groups. Among the participants with a median follow-up of 2.17 years, 4511 (37.2%) participants had MAFLD at baseline, among which 3954 (87.7%), 123 (2.7%), and 434 (9.6%) were OW-, lean- and DM-MAFLD, respectively. Analyses using linear regression models confirmed that compared with the non-MAFLD group, the elevated baPWV change rates (cm/s/year) were 12.87 (8.81-16.94), 25.33 (7.84-42.83) and 38.49 (27.88-49.10) in OW, lean and DM-MAFLD, respectively, while the increased change proportions (%) were 1.53 (1.10-1.95), 3.56 (1.72-5.40) and 3.94 (2.82-5.05), respectively. Similar patterns were observed when these two baPWV parameters were transformed in the form of the greatest increase using Cox proportional hazards model analyses. Furthermore, the risk of arterial stiffness progression across MAFLD subtypes presented a significant, gradient, inverse relationship in the order of DM-, lean-, OW with metabolic abnormalities (MA)-, and OW without MA-MAFLD. CONCLUSION: MAFLD, especially DM-MAFLD and lean-MAFLD, was significantly associated with arterial stiffness progression, providing evidence that stratification screening and surveillance strategies for CVD risk have important clinical implications.

Linkage of cell division cycle 42 with clinical features, treatment response and survival in adult Philadelphia chromosome negative acute lymphoblastic leukemia.

Cell division cycle 42 (CDC42) regulates the progression of leukemia via mediating proliferation and immune evasion of malignant cells. The study aimed to investigate the correlation of CDC42 with clinical features, treatment response, event-free survival (EFS) and overall survival (OS) in adult Philadelphia chromosome negative acute lymphoblastic leukemia (Ph- ALL) patients. CDC42 expression in bone marrow mononuclear cells was detected in 78 adult Ph- ALL patients and 10 donors using real-time reverse transcriptase-polymerase chain reaction. CDC42 was increased in adult Ph- ALL patients compared with donors (p < .001). Besides, elevated CDC42 was linked with pro-B ALL or early-T ALL (p = .038) and white blood cell (WBC) elevation at diagnosis (p = .025). Fifty (64.1%) and 23 (29.5%) patients had complete remission (CR) at 1 month and minimal residual disease (MRD) after CR, respectively. CDC42 was inversely associated with CR at 1 month (p = .034), but not MRD after CR (p = .066). Concerning survival, patients with CDC42 ≥ 3.310 (cut by median value in patients) showed a shortened EFS (p = .006) and OS (p = .036) compared to those with CDC42 < 3.310. In detail, patients with CDC42 ≥ 3.310 and CDC42 < 3.310 had 5-year EFS rate of 29.9% and 45.4%, and 5-year OS rate of 39.4% and 63.6%, correspondingly. Further multivariate Cox's regression analyses revealed that CDC42 ≥ 3.310 was independently related to shorter EFS (hazard ratio = 2.933, p = .005). Elevated CDC42 is related with pro-B ALL or early-T ALL, WBC elevation at diagnosis, unfavorable treatment response and worse survival in adult Ph- ALL patients.

Not only baseline but cumulative exposure of remnant cholesterol predicts the development of nonalcoholic fatty liver disease: a cohort study.

BACKGROUND AND AIM: Remnant cholesterol (remnant-C) mediates the progression of major adverse cardiovascular events. It is unclear whether remnant-C, and particularly cumulative exposure to remnant-C, is associated with nonalcoholic fatty liver disease (NAFLD). This study aimed to explore whether remnant-C, not only baseline but cumulative exposure, can be used to independently evaluate the risk of NAFLD. METHODS: This study included 1 cohort totaling 21,958 subjects without NAFLD at baseline who underwent at least 2 repeated health checkups and 1 sub-cohort totaling 2,649 subjects restricted to those individuals with at least 4 examinations and no history of NAFLD until Exam 3. Cumulative remnant-C was calculated as a timeweighted model for each examination multiplied by the time between the 2 examinations divided the whole duration. Cox regression models were performed to estimate the association between baseline and cumulative exposure to remnant-C and incident NAFLD. RESULTS: After multivariable adjustment, compared with the quintile 1 of baseline remnant-C, individuals with higher quintiles demonstrated significantly higher risks for NAFLD (hazard ratio [HR] 1.48, 95%CI 1.31-1.67 for quintile 2; HR 2.07, 95%CI 1.85-2.33 for quintile 3; HR 2.55, 95%CI 2.27-2.88 for quintile 4). Similarly, high cumulative remnant-C quintiles were significantly associated with higher risks for NAFLD (HR 3.43, 95%CI 1.95-6.05 for quintile 2; HR 4.25, 95%CI 2.44-7.40 for quintile 3; HR 6.29, 95%CI 3.59-10.99 for quintile 4), compared with the quintile 1. CONCLUSION: Elevated levels of baseline and cumulative remnant-C were independently associated with incident NAFLD. Monitoring immediate levels and longitudinal trends of remnant-C may need to be emphasized in adults as part of NAFLD prevention strategy.

The effect of enhanced recovery after lung cancer surgery combined with fine surgical nursing on rehabilitation.

Objectives: To analyse the enhanced recovery after surgery approach combined with fine surgical nursing on recovery time, pain, sleep quality and satisfaction with care after lung cancer surgery. METHODS: The cross-sectional study was conducted at the Nanjing Chest Hospital, China, from October 2019 to March 2022, and comprised non-small cell lung cancer patients undergoing single-port video-assisted thoracoscopic surgery. Patients receiving fine surgical nursing in addition to conventional enhanced recovery after surgery formed the intervention group A, while those receiving the conventional enhanced recovery after surgery care alone formed control group B. Intraoperative blood loss, operative time, extubation time and length of stay values were noted for both the groups using standard scales. Nursing satisfaction and the incidence of adverse reactions in the two groups were also noted. Data was analysed using SPSS 23. RESULTS: Of the 99 patients, 46(46.5%) were in group A; 23(50%) males and 23(50%) females with mean age 70.3±4.8 years and mean body mass index 26.76±2.55kg/m2. There were 53(53.5%) patients in group B: 16(30.2%) males and 37(69.8%) females with mean age 69.9±4.4 years and mean body mass index 25.93±2.40kg/m2 (p>0.05). Intraoperative blood loss, operative time, postoperative extubation time and length of stay in group A were lower than those in group B (p<0.05). Pain and sleep quality values in group A were lower, while health status value was higher than group B (p<0.05). Group A had significantly higher nursing satisfaction compared to group B (p<0.05). Conclusion: The use of enhanced recovery after surgery combined with fine surgical nursing in patients with nonsmall cell lung cancer after video-assisted thoracoscopic surgery promoted postoperative recovery.

Autophagy impairment is involved in midazolam-induced lipid droplet accumulation and consequent phagocytosis decrease in BV2 cells.

An increasing number of experimental and clinical observation suggest that the use of anaesthetics is closely associated with postoperative central nervous system (CNS) complications, such as delirium and cognitive dysfunction. Brain energy rescue is an emerging therapeutic strategy for central nervous system disease (CNSDs). However, the effect of anaesthetics on nerve cell energy utilisation, especially microglia, and its potential effects on cell function still unclear. Elucidating the effects of anaesthetics on lipid droplets, which are specific lipid storage organs, and phagocytosis of microglia is crucial to discover a new therapeutic concept for postoperative CNS complications. Here, we studied the effects of the commonly used anaesthetic midazolam on lipid droplets and phagocytosis in immortalised microglial BV2 cells. Lipid droplets were assessed by flow cytometry and triglyceride quantification. The phagocytosis of BV2 cells was evaluated by detecting their phagocytosis by latex beads. Additionally, the autophagy of BV2 cells was evaluated by western blot and observation under microscopy. Our results showed that midazolam caused lipid droplet accumulation and reduced phagocytosis in BV2 cells, and inhibition of lipid droplet accumulation partially restored phagocytosis. Furthermore, midazolam blocks autophagic degradation by increasing phosphorylated TFEB in BV2 cells, inhibition of midazolam-increased phosphorylated TFEB might contribute to the improvement of autophagic flux by rapamycin. Moreover, promoting autophagy reverse the lipid droplet accumulation and phagocytosis decrease. This study suggests autophagy is a target for attenuating lipid droplet accumulation, normal degradation of lipid droplets is important for maintaining microglia phagocytosis and attenuating the side effects of midazolam on the CNS.

Pre-treatment systemic immune-inflammation index as a non-invasive biomarker for predicting clinical outcomes in patients with renal cell carcinoma: a meta-analysis of 20 studies.

INTRODUCTION: To systematically assess the predictive significance of systemic immune-inflammation index (SII) in renal cell carcinoma (RCC). METHODS: Relevant studies published before November 2022 were retrieved from public databases. Hazard ratio (HR), standardised mean difference (SMD) and relative risk (RR) were calculated to estimate associations of SII with prognosis, treatment responses and clinicopathological features. RESULTS: Twenty studies involving 6887 patients were eligible. The meta-analysis results revealed a high SII level was associated with worse overall survival (HR: 1.45, p < 0.001), progression-free survival (HR: 1.63, p = 0.001), cancer-specific survival (HR: 1.86, p < 0.001), lower overall response rate (RR: 0.62, p = 0.003), disease control rate (RR: 0.69, p = 0.002), larger tumour size (SMD: 0.39, p = 0.001), poorer IMDC risk (RR: 7.09, p < 0.001), higher Fuhrman grade (RR: 1.54, p = 0.004), tumour stage (RR: 1.67, p = 0.045), the presence of distant metastasis (brain: RR, 2.04, p = 0.001; bone: RR, 1.33, p = 0.024) and tumour necrosis (RR: 1.57, p = 0.031). Subgroup analysis showed SII predicted OS and PFS for non-Asian, but CSS for both Asian and non-Asian populations. CONCLUSION: Pre-treatment SII may be a promising predictor of clinical outcomes for RCC patients.

Establishment of a model for predicting preterm birth based on the machine learning algorithm.

BACKGROUND: The purpose of this study was to construct a preterm birth prediction model based on electronic health records and to provide a reference for preterm birth prediction in the future. METHODS: This was a cross-sectional design. The risk factors for the outcomes of preterm birth were assessed by multifactor logistic regression analysis. In this study, a logical regression model, decision tree, Naive Bayes, support vector machine, and AdaBoost are used to construct the prediction model. Accuracy, recall, precision, F1 value, and receiver operating characteristic curve, were used to evaluate the prediction performance of the model, and the clinical application of the model was verified. RESULTS: A total of 5411 participants were included and were used for model construction. AdaBoost model has the best prediction ability among the five models. The accuracy of the model for the prediction of "non-preterm birth" was the highest, reaching 100%, and that of "preterm birth" was 72.73%. CONCLUSIONS: By constructing a preterm birth prediction model based on electronic health records, we believe that machine algorithms have great potential for preterm birth identification. However, more relevant studies are needed before its application in the clinic.

Highly specific neutrophil-mediated delivery of albumin nanoparticles to ectopic lesion for endometriosis therapy.

Endometriosis is an estrogen-dependent chronic inflammatory disease. Hormonal and surgical treatments are the most commonly used clinical therapies, but they have many sides effects or are traumatic to the body. Therefore, specific drugs for endometriosis treatment are urgently needed to develop. In this study, we identified two features of endometriosis, namely the continuous recruitment of neutrophils into the ectopic lesions and the higher uptake of glucose by ectopic cells. For the above features, we designed a glucose oxidase-loaded bovine serum albumin nanoparticle (BSA-GOx-NPs) that is inexpensive and facilitates large-scale production. After injection, BSA-GOx-NPs were high specifically delivered to ectopic lesions in a neutrophil-dependent manner. Furthermore, BSA-GOx-NPs deplete glucose and induce apoptosis in the ectopic lesions. Whereupon BSA-GOx-NPs produced excellent anti-endometriosis effects when administrated in both acute and chronic inflammatory phases. These results reveal for the first time that the neutrophil hitchhiking strategy is effective in chronic inflammatory disease and provide a non-hormonal and easy-to-achieve approach for endometriosis treatment.

Parachute-like pull-through anastomosis for low rectal cancer: a new method for preservation of anal function.

BACKGROUND: With recent improvements in surgical technique, oncological outcomes of low rectal cancer have improved over time. But the QoL impairment as a result of anal functional disorder cannot be ignored. And the incidence of anastomosis-related complications cannot be ignored. To address these problems, a personal technique for pull-through coloanal anastomosis (parachute-like intussuscept pull-through anastomosis) was introduced and evaluated. This technique can relatively reduce surgical complications, minimize the impact of anal function, and obviate a colostomy creation. METHODS: Between June 2020 and April 2021, 14 consecutive patients with rectal cancer underwent laparoscopic-assisted resection of rectal cancer in our hospital. Parachute-like pull-through anastomosis method was performed in all patients. Anal function, perioperative details, and postoperative outcomes were analyzed. RESULTS: The mean (SD) operative time of first stage was 282.1 min (range 220-370) with an average estimated blood loss of 90.3 mL (range 33-200). And the mean (SD) operative time of second was 46 min (range 25-76) with an average estimated blood loss of 16.1 mL (range 5-50). Wexner scores declined significantly during the median follow-up of 18 months. Four postoperative anastomosis-related complications occurred in 14 patients, including perianastomotic abscess: 1 case (7%), anastomotic stricture: 1 case (7%), and colonic ischemia of the exteriorized colonic segment: 2 cases (14%). CONCLUSION: The results suggest that the method can facilitate safe and easy completion of coloanal anastomosis, using parachute-like pull-through anastomosis, with acceptable anal function.

Humic acids alleviate aflatoxin B1-induced hepatic injury by reprogramming gut microbiota and absorbing toxin.

Aflatoxin B1 (AFB1) is a hepatotoxic fungal metabolite that is widely present in food and can cause liver cancer. As a potential detoxifier, naturally occurring humic acids (HAs) may be able to reduce inflammation and restructure the gut microbiota composition; however, little is known about the mechanism of HAs detoxification as applied to liver cells. In this study, HAs treatment alleviated AFB1-induced liver cell swelling and the infiltration of inflammatory cells. HAs treatment also reinstated various enzyme levels in the liver disturbed by AFB1 and substantially alleviated AFB1-caused oxidative stress and inflammatory responses by enhancing immune functions in mice. Moreover, HAs increased the length of the small intestinal and villus height to restore intestinal permeability, which is impaired by AFB1. In addition, HAs reconstructed the gut microbiota, increasing the relative abundance of Desulfovibrio, Odoribacter, and Alistipes. In vitro and in vivo assays demonstrated that HAs could efficiently remove AFB1 by absorbing the toxin. Therefore, HAs treatment can ameliorate AFB1-induced hepatic injury by enhancing gut barrier function, regulating gut microbiota, and adsorbing toxin.

First Report of Pseudomonas oryzihabitans Causing Walnut Leaf Spot Disease in China.

China ranks first in the production and harvest area of walnut (Juglans regia L.) worldwide. Currently, the poor health and low yield of walnut caused by pathogen infection is of concern. In 2022, severe walnut leaf spot disease was observed on the seedlings of four walnut nurseries (0.08 to 0.23 ha) in Liaocheng, Shandong, China, with an average incidence of 48.6% (from 34.6% to 65.3% on the cultivar Xiangling). From August to October, leaf spots mainly appeared on the edges of the leaflets, and occasionally between veins. The lesions were initially soft and rotten, and then light brown, round to semi-circular. Subsequently, the adjacent lesions fused, and the edges of the leaflets and entire leaflets showed symptoms of browning and wilting. For pathogen isolation, five leaflets with representative symptoms from one of the nurseries were collected and wiped three times with sterile absorbent cotton dipped in 75% alcohol and washed with distilled water. Leaflet pieces at the junction of the lesion and healthy tissues were removed, crushed in a sterile mortar, and soaked in a small amount of distilled water for 10 min. The diseased tissue suspension was streaked on a nutrient agar medium (NA) with a sterile inoculation ring and incubated at 28°C for 24 to 72 h. The bacterial colonies obtained were further cultured on NA. The purified colonies were uniform in shape, round, and yellow, with a raised, shiny surface and smooth margin. The isolates were Gram-negative, and the electron microscope analysis showed that the pathogens were short rods (0.35 to 0.52 × 0.90 to 1.24 µm, average = 0.44 ± 0.05 × 1.08 ± 0.11 µm, n = 25). For bacterial species identification, a single-colony culture was subjected to genomic DNA extraction and gene amplification and sequencing of 16S rRNA, rpoD, and gyrB. The universal primers 27F/1492R (Lane 1991) were used to amplify the 16S rRNA gene and the specific primers 70F/70R and UP-1E/APrU (Yamamoto et al. 2000) were used to amplify the rpoD and gyrB genes, respectively. In the BLAST analysis, the 16S rRNA sequence (GenBank OR195734) of the isolate shared 99% similarity (1409/1410 bp) with Pseudomonas oryzihabitans strain IAM 1568T (AM262973.1), and the rpoD (OR709708) and gyrB (OR709707) sequences showed >98% identity to rpoD (707/717 bp; FN554494.1) and gyrB (787/801 bp; FN554210.1) of P. oryzihabitans strain LMG 7040T. Based on the above results, the isolated bacterium was identified as P. oryzihabitans. For the pathogenicity test, healthy leaflets from 10 two-year-old potted walnut seedlings (cv. Xiangling) were used as inoculation materials. The leaflets were punctured with a sterile inoculation needle of 0.4 mm, and three small holes on each leaflet at an interval of about 5 mm were covered with a piece of sterile cotton. A bacterial suspension (1 ml) at 107 CFU/ml was spread onto the cotton, and wrapped with plastic film for 24 h. Water was used as a negative control. The inoculations were performed five times. Plants were grown outdoors at a daily average temperature of 22°C with relative humidity over 45%. Two days after inoculation, the disease began to develop in the leaflets with similar symptoms to those observed in the field. In contrast, control plants remained healthy and symptomless. Bacteria were reisolated from the inoculated walnut plants, and the morphology and 16S rRNA gene sequences of the isolates were the same as those of the original strains. Since it was discovered as an opportunistic human pathogenic bacterium in the 1970s (Keikha et al. 2019), P. oryzihabitans has also been shown to cause certain plant diseases, such as panicle blight and grain discoloration on rice (Hou et al. 2020), fruit black rot on prickly ash (Liu et al. 2021), and stem and leaf rot on muskmelon (Li et al. 2021). As far as we know, this is the first report of P. oryzihabitans causing walnut leaf spot disease in China. Leaf spot caused by P. oryzihabitans may be a threat to walnut cultivation, and this report of its occurrence is the first step in determining potential spread and effective control measures.

Effects of intervention integrating physical literacy into active school recesses on physical fitness and academic achievement in Chinese children.

Background/Objective: The aim of this study was to examine the effects of school-based intervention integrating physical literacy (PL) into active school recesses (ASR) on physical fitness (i.e., body composition, 20-m shuttle run, 50-m run, rope skipping, sit and reach, handgrip) and academic achievement (i.e., academic result of Chinese and Mathematics) in Chinese children. Methods: A total of 357 children (mean age: 7.8 ± 0.7 years; boys: 50.4%) were recruited from two schools and these two schools were randomly assigned as the intervention group (IG) and the control group (CG), respectively. The IG consisted of 155 children (mean age: 7.9 ± 0.7 years, boys: 51.0%), and 202 children (mean age: 7.8 ± 0.7 years; boys: 50%) were allocated to the CG. Children in the IG received a 10-week intervention integrating PL that was conducted during ASR. In the CG, children's regular school activity was remained during the intervention period. Generalized estimating equation was performed to compare the levels of physical fitness and academic achievement between the IG and the CG after intervention. Results: Regarding physical fitness, there was a significant group × time interaction on 20-m shuttle run (ß = -3.89, 95% CI [-5.08; -2.71], p < 0.001) and handgrip (ß = -0.70, 95% CI [-1.20; -0.20], p = 0.006). After intervention, children in the IG had a greater increase than the CG (p < 0.001) in terms of 20-m shuttle run and handgrip. In addition, the post-test analysis indicated that performance of children in the IG was significantly greater than those in the CG (20-m shuttle run: p < 0.001, handgrip: p = 0.002). There was a significant group × time interaction on academic result of Chinese (ß = -1.21, 95% CI [-1.91; -0.56], p = 0.001) and academic result of Mathematics (ß = 16.71, 95% CI [15.14; 18.143], p < 0.001). Statistically significant positive difference in post-test was observed in academic result of Mathematics between the IG and the CG (p = 0.012). Conclusion: The results of this intervention study indicate that intervention integrating PL into ASR could bring a promising effect on physical fitness and academic achievement in children. It is recommended that future studies are necessary to assess the effects of ASR-based PL intervention on physical and cognitive outcomes using a wide range of sample.

Grpel2 alleviates myocardial ischemia/reperfusion injury by inhibiting MCU-mediated mitochondrial calcium overload.

Mitochondrial calcium ([Ca2+]m) overload is considered a major trigger of cardiomyocyte death during myocardial ischemia/reperfusion (I/R) injury. Grpel2 is located in mitochondria and facilitates the mtHSP70 protein folding cycle in oxidative stress. However, Grpel2 expression during I/R injury and its impact on I/R injury remain poorly understood. This study explored the role of Grpel2 in I/R injury and its underlying mechanism. Mice were intramyocardially injected with recombinant adenovirus vectors to knockdown cardiac Grpel2 expression, and a myocardial I/R model was established. We confirmed that cardiac Grpel2 is upregulated during I/R injury. Cardiac-specific Grpel2 knockdown exacerbates mitochondrial fission, cardiomyocyte death and cardiac contractile dysfunction induced by I/R injury. Moreover, our study revealed that Grpel2 knockdown increased both MCU expression and [Ca2+]m content. Excessive mitochondrial fission and apoptosis were rescued by Ru360, an inhibitor of MCU opening. In summary, our findings suggest that Grpel2 alleviates myocardial ischemia/reperfusion injury by inhibiting MCU-mediated mitochondrial calcium overload and provide new insights into the mechanism of MCU-mediated [Ca2+]m homeostasis during I/R injury.

A promising type-II ß-AsP/g-C6N6 van der Waals heterostructure photocatalyst for water splitting: a first-principles study.

Photocatalytic water splitting, which can use abundant and clean solar energy, is friendly to the environment and consumes less energy. This work predicts the type-II ß-AsP/g-C6N6 van der Waals (vdW) heterostructure as a promising photocatalyst for water splitting using first-principles calculations. Compared with the g-C6N6 monolayer, the ß-AsP/g-C6N6 heterostructure not only can effectively separate photogenerated electron and hole pairs but also shows considerable light absorption and better photocatalyst performances. The optical absorption coefficient of the ß-AsP/g-C6N6 heterostructure has also extremely increased, more than ten times that of the g-C6N6 monolayer. The ß-AsP/g-C6N6 heterostructure with little compression (-2%) could be conducive to the hydrogen evolution reaction with a Gibbs free energy closer to zero (-0.46 eV) compared to monolayers. The oxygen evolution reaction has a low theoretical overpotential of 0.63 V. These results indicate that it exhibits favorable performances as a photocatalyst. This work predicts the possible application of the ß-AsP/g-C6N6 heterostructure as a photocatalyst and expands the scope of renewable energy devices.

Perceived social support in Chinese family caregivers of patients with dementia.

AIM: This study aimed to describe levels of social support and explore the factors predictive of social support for Chinese family caregivers of patients with dementia. BACKGROUND: Social support levels and their predictive factors in Chinese dementia caregivers have not been well documented, which need to be further clarified to provide a basis for creating effective social support strategies. METHODS: This was a cross-sectional study with 91 participants who completed a demographic questionnaire and the Social Support Rating Scale from 2015 to 2016. RESULTS: Chinese family caregivers of patients with dementia received moderate social support. Caregivers' subjective support domain scores and support utilization domain scores were significantly lower than those of the normal Chinese population, whereas caregivers' total social support scores were higher than those of the normal Chinese population. Family caregivers' monthly household income, educational level and place of residence were predictors of their own social support. CONCLUSION: Social support in Chinese caregivers of patients with dementia needs to be improved, especially the subjective support and support utilization. Healthcare professionals should pay special attention to caregivers with a lower monthly household income and educational level and caregivers who lived in the suburban area.

Maternal Mental Health Status and Approaches for Accessing Antenatal Care Information During the COVID-19 Epidemic in China: Cross-Sectional Study.

BACKGROUND: China was the first country in the world to experience a large-scale COVID-19 outbreak. The rapid spread of the disease and enforcement of public health measures has caused distress among vulnerable populations such as pregnant women. With a limited understanding of the novel, emerging infectious disease, pregnant women have sought ways to access timely and trusted health care information. The mental health status of pregnant women during this public health emergency, as well as how they responded to the situation and where and how they obtained antenatal care information, remain to be understood. OBJECTIVE: This study aimed to evaluate the mental health status of pregnant women during the COVID-19 epidemic in China by measuring their perceived stress, anxiety, and depression levels; explore the approaches used by them to access antenatal health care information; and determine their associations with maternal mental health status. METHODS: We conducted a web-based, cross-sectional survey to assess the mental health status of Chinese pregnant women by using the validated, Chinese version of Perceived Stress Scale, Self-Rating Anxiety Scale, and Edinburgh Depression Scale. We also collected information on the various approaches these women used to access antenatal care information during the early stage of the COVID-19 epidemic, from February 5 to 28, 2020. RESULTS: A total of 1873 pregnant women from 22 provinces or regions of China participated in the survey. The prevalence of perceived stress, anxiety, and depression among these participants was 89.1% (1668/1873; 95% CI 87.6%, 90.4%), 18.1% (339/1873; 95% CI 16.4%, 19.9%), and 45.9% (859/1873; 95% CI 43.6%, 48.1%), respectively. Hospitals' official accounts on the Chinese social media platforms WeChat and Weibo were the most popular channels among these pregnant women to obtain antenatal care information during the COVID-19 outbreak. Access to antenatal care information via the hospitals' official social media accounts was found to be associated with a significantly lower risk of perceived stress (adjusted odds ratio [aOR] 0.46, 95% CI 0.30-0.72; P=.001), anxiety (aOR 0.53, 95% CI 0.41-0.68; P<.001), and depression (aOR 0.73, 95% CI 0.59-0.91; P=.005). Access to health care information via hospital hotlines or SMS was found to be significantly associated with a lower risk of anxiety only (OR 0.77, 95% CI 0.60-0.98; P=.04). CONCLUSIONS: During the COVID-19 outbreak in China, pregnant women experienced high levels of perceived stress, anxiety, and depression. During such public health emergencies, mental health care services should be strengthened to reassure and support pregnant women. Specific information targeted at pregnant women, including information on how to cope in an emergency or major disease outbreak, developed and disseminated by health care institutions via social media platforms could be an effective way to mitigate mental health challenges and ensure epidemic preparedness and response in the future.

Prodigiosin of Serratia marcescens ZPG19 Alters the Gut Microbiota Composition of Kunming Mice.

Prodigiosin is a red pigment produced by Serratia marcescens with anticancer, antimalarial, and antibacterial effects. In this study, we extracted and identified a red pigment from a culture of S. marcescens strain ZPG19 and investigated its effect on the growth performance and intestinal microbiota of Kunming mice. High-performance liquid chromatography/mass spectrometry revealed that the pigment had a mass-to-charge ratio (m/z) of 324.2160, and thus it was identified as prodigiosin. To investigate the effect of prodigiosin on the intestinal microbiota, mice (n = 5) were administered 150 µg/kg/d prodigiosin (crude extract, 95% purity) via the drinking water for 18 days. Administration of prodigiosin did not cause toxicity in mice. High-throughput sequencing analysis revealed that prodigiosin altered the cecum microbiota abundance and diversity; the relative abundance of Desulfovibrio significantly decreased, whereas Lactobacillus reuteri significantly increased. This finding indicates that oral administration of prodigiosin has a beneficial effect on the intestinal microbiota of mice. As prodigiosin is non-toxic to mouse internal organs and improves the mouse intestinal microbiota, we suggest that it is a promising candidate drug to treat intestinal inflammation.

Ubiquitin-specific protease 7 is a druggable target that is essential for pancreatic cancer growth and chemoresistance.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, and most patients die within one year after diagnosis. This cancer is resistant to almost all current therapies, so there is an urgent need to identify novel druggable targets. Ubiquitin-specific protease 7 (USP7) is a deubiquitinase that functions in carcinogenesis, but its role in PDAC is unknown. Our experiments indicated that several subtypes of PDAC cells are sensitive to USP7 inhibition. In particular, pharmaceutical inhibition of USP7 by the small molecule P22077 attenuated PDAC cell growth and induced cell death in vitro and in vivo. Pharmaceutical inhibition of USP7 in P22077-resistant PDAC cells allowed them to overcome chemoresistance. Genetic silencing experiments supported the importance of USP7 in the pathogenesis of PDAC. In particular, genetic disruption of USP7 greatly reduced cell proliferation and chemoresistance in vitro and prevented PDAC growth in vivo. Protein profiling by mass spectrometry (MS) indicated USP7 was associated 4 ontology terms: translation, localization and protein transporting, nucleotide or ribonucleotide binding, and ubiquitin-dependent catabolic processes. Puromycin labeling indicated that P22077 greatly reduced protein synthesis, and transcriptional analysis indicated that P22077 significantly altered the extracellular space matrix. In summary, we provided multiple lines of evidence which indicate that USP7 plays a critical role in PDAC, and may therefore be a suitable target for treatment of this cancer.