A Brief Intervention With Instant Messaging or Regular Text Messaging Support in Reducing Alcohol Use: A Randomized Clinical Trial.

Importance: Alcohol use is prevalent among university students. Mobile instant messaging apps could enhance the effectiveness of an alcohol brief intervention (ABI), but the evidence is scarce. Objective: To evaluate the effectiveness of an ABI plus 3 months of mobile chat-based instant messaging support for alcohol reduction in university students at risk of alcohol use disorder. Design, Setting, and Participants: In this randomized clinical trial, 772 students at risk of alcohol use disorder (Alcohol Use Disorders Identification Test [AUDIT] score ≥8) were recruited from 8 universities in Hong Kong between October 15, 2020, and May 12, 2022. Participants were randomly assigned 1:1 to either the intervention or control group. Interventions: Both groups received the same ABI at baseline, which consisted of face-to-face or video conferencing with research nurses who delivered personalized feedback based on the participant's AUDIT risk level, along with a 12-page booklet describing the benefits of alcohol reduction and the harmful effects of alcohol on health and social well-being. The intervention group then received 3 months of chat-based instant messaging support on alcohol reduction guided by behavioral change techniques. The control group received 3 months of short message service (SMS) messaging on general health topics. Main Outcomes and Measures: All outcomes were self-reported. The primary outcome was alcohol consumption in grams per week at 6 months of follow-up. By definition, 1 alcohol unit contains 10 g of pure alcohol. Secondary outcomes at the 6-month follow-up included changes in AUDIT score, weekly alcohol consumption, intention to drink in the next 30 days, drinking frequency and any binge or heavy drinking in the past 30 days, and self-efficacy of quitting drinking. The primary analysis followed the intention-to-treat principle, and linear regression (reported as unstandardized coefficient B) and logistic regression (reported as odds ratios) were used to compare the primary and secondary outcomes between the intervention and control groups. Results: The study included 772 students (mean [SD] age, 21.1 [3.5] years; 395 females [51.2%]) who were randomly assigned to either the intervention (n = 386) or control (n = 386) group. In the intention-to-treat analysis, the intervention group had lower alcohol consumption in grams per week (B, -11.42 g [95% CI, -19.22 to -3.62 g]; P = .004), a lower AUDIT score (B, -1.19 [95% CI, -1.63 to -0.34]; P = .003), reduced weekly alcohol unit consumption (B, -1.14 [95% CI, -1.92 to -0.36]; P = .004), and less intention to drink (odds ratio, 0.66 [95% CI, 0.47 to 0.92]; P = .01) at the 6-month follow-up compared with the control group. In analyses adjusted for baseline characteristics, interacting at least once with the research nurse on the instant messaging application resulted in lower estimated alcohol consumption in grams per week (adjusted B, -17.87 g [95% CI, -32.55 to -3.20 g]; P = .01), lower weekly alcohol unit consumption (adjusted B, -1.79 [95% CI, -3.25 to -0.32]; P = .02), and a lower AUDIT score (adjusted B, -0.53 [95% CI, -1.87 to -0.44]; P = .01) at 6 months. Conclusions and Relevance: Results of this randomized clinical trial indicate that mobile chat-based instant messaging support for alcohol reduction in addition to an ABI was effective in reducing alcohol consumption in university students in Hong Kong at risk of alcohol use disorder. Trial Registration: ClinicalTrials.gov Identifier: NCT04025151.

Identification of odorant-binding proteins and functional analysis of antenna-specific BhorOBP28 in Batocera horsfieldi (Hope).

BACKGROUND: The important wood-boring pest Batocera horsfieldi has evolved a sensitive olfactory system to locate host plants. Odorant-binding proteins (OBPs) are thought to play key roles in olfactory recognition. Therefore, exploring the physiological function of OBPs could facilitate a better understanding of insect chemical communications. RESULTS: In this research, 36 BhorOBPs genes were identified via transcriptome sequencing of adults' antennae from B. horsfieldi, and most BhorOBPs were predominantly expressed in chemosensory body parts. Through fluorescence competitive binding and fluorescence quenching assays, the antenna-specific BhorOBP28 was investigated and displayed strong binding affinities forming stable complexes with five volatiles, including (+)-α-Pinene, (+)-Limonene, ß-Pinene, (-)-Limonene, and (+)-Longifolene, which could also elicit conformation changes when they were interacting with BhorOBP28. Batocera horsfieldi females exhibited a preference for (-)-Limonene, and a repellent response to (+)-Longifolene. Feeding dsOBP19 produced by a bacteria-expressed system with a newly constructed vector could lead to the knockdown of BhorOBP28, and could further impair B. horsfieldi attraction to (-)-Limonene and repellent activity of (+)-Longifolene. The analysis of site-directed mutagenesis revealed that Leu7, Leu72, and Phe121 play a vital role in selectively binding properties of BhorOBP28. CONCLUSION: By modeling the molecular mechanism of olfactory recognition, these results demonstrate that BhorOBP28 is involved in the chemoreception of B. horsfieldi. The bacterial-expressed dsRNA delivery system gains new insights into potential population management strategies. Through the olfactory process concluded that discovering novel behavioral regulation and environmentally friendly control options for B. horsfieldi in the future. © 2024 Society of Chemical Industry.

Bispecific fibrous glue synergistically boosts vascular normalization and antitumor immunity for advanced renal carcinoma therapy.

Immune checkpoint blockade therapy represented by programmed cell death ligand 1 (PD-L1) inhibitor for advanced renal carcinoma with an objective response rate (ORR) in patients is less than 20%. It is attributed to abundant tumoral vasculature with abnormal structure limiting effector T cell infiltration and drug penetration. We propose a bispecific fibrous glue (BFG) to regulate tumor immune and vascular microenvironments simultaneously. The bispecific precursor glue peptide-1 (pre-GP1) can penetrate tumor tissue deeply and self-assemble into BFG in the presence of neuropilin-1 (NRP-1) and PD-L1. The resultant fibrous glue is capable of normalizing tumoral vasculature as well as restricting immune escape. The pre-GP1 retains a 6-fold higher penetration depth than that of antibody in the multicellular spheroids (MCSs) model. It also shows remarkable tumor growth inhibition (TGI) from 19% to 61% in a murine advanced large tumor model compared to the clinical combination therapy. In addition, in the orthotopic renal tumor preclinical model, the lung metastatic nodules are reduced by 64% compared to the clinically used combination. This pre-GP1 provides a promising strategy to control the progression and metastasis of advanced renal carcinoma.

Switchable Enantioselectivity in Conjugate Alkyne Addition of ß,γ-Unsaturated α-Keto Esters by Asymmetric Binary Acid Catalysis.

Switchable enantioselectivity was uncovered in the enantioselective catalytic conjugate addition of ß,γ-unsaturated α-keto esters with terminal alkynes to the chiral Lewis acid complex of In(BF4)3 and chiral phosphoric acid.

Effects of dietary supplementation of grape seed extract in comparison with excessive level of vitamin E on growth performance and antioxidant function of broilers.

The present study was carried out to evaluate the effects of dietary vitamin E (VE) or grape seed extract (GSE) on the growth performance and antioxidant function of broilers. Two hundred sixteen broiler chicks were randomly assigned to 3 diets: diet supplemented with oxidized rice bran oil (CN group), CN group with 25 mg/kg VE or 100 mg/kg GSE. Dietary VE or GSE improved the growth performance, reverted the disturbed levels of liver antioxidant enzymes, and reduced liver damage of broilers fed oxidized rice bran oil. The mRNA data showed that supplementation of VE or GSE enhanced the antioxidant capacity of the broiler liver through activation of the Keap1-Nrf2/ARE signaling pathway. The results suggested that VE and GSE can increase weight gain, improve the oxidative status, and alleviate liver injury in broiler chicken fed oxidized rice bran oil.

Prolonged oral intake of green tea polyphenols attenuates delirium-like behaviors in mice induced by anesthesia/surgery.

Postoperative delirium (POD) is a severe postoperative complication characterized by delirium-like symptoms. So far, no effective preventable strategy for POD prevention has been identified. Reports show that the consumption of green tea polyphenols (GTP) is associated with better cognitive function by modulating the composition of gut microbiota. Whether GTP also play a role in alleviating POD through gut microbiota is unknown. Herein, we studied the effect of prolonged (eight weeks) GTP intake on postoperative delirium in C57BL/6 mice with laparotomies under isoflurane anesthesia (anesthesia/surgery). We subsequently investigated anesthesia/surgery caused behavioral changes and increased the expression of malondialdehyde (MAD), an oxidative stress marker, and the activities of superoxide dismutase (SOD), an antioxidant marker, in the mice at 6 h after anesthesia/surgery. However, GTP administration reversed these changes and alleviated anesthesia/surgery-induced decrease in the abundance of gut bacterial genera, Roseburia. Further, fecal microbiota transplant demonstrated that compared with mice in the control group, treatment of C57BL/6 mice with feces from GTP-treated mice had a slight effect on the behavioral changes of mice. These data suggest that daily consumption of GTP could protect against anesthesia/surgery-induced behavioral changes, which is closely associated with gut microbiota modification by GTP.

Gamified Strength Recognition and Quiz to Enhance COVID-19 Prevention Knowledge and Behaviors, and Family Well-Being: Web-Based Pilot Intervention.

Background: Promoting COVID-19 prevention is key to pandemic control and innovative interventions can help communicate reliable science to the public. Under the Hong Kong Jockey Club SMART Family-Link Project, we developed and evaluated a pilot intervention for promoting COVID-19 prevention through a web-based family game, guided by the Theory of Planned Behavior and a strength-based approach. Methods: The "SMART Epidemic prevention" pilot theme was launched to the public on September 21, 2020 for 4 weeks. The game had two parts: (i) strength recognition and (ii) quiz questions on knowledge and behaviors about COVID-19 prevention. Simple baseline, in-game, and postgame evaluation assessed players' perceived knowledge, behaviors, family well-being, game satisfaction, and perceived benefits. Results: Of 86 registered families, 55 played actively, including 212 players (51% female, 35% aged below 18) who self-identified as children (44%), parents (39%), and grandparents (11%). In weeks 1 and 4, an average of 7 and 18 game rounds were played per family, and 86.6% and 75.9% of rounds had perfect (2) behavior matches. Postgame evaluation with 51 families showed improvements in epidemic prevention knowledge and behaviors, family communication, family happiness (all P < 0.001), and family relationship (P = 0.002) with small effect sizes (0.15-0.29). Overall game satisfaction was rated 4.49 (scale of 1-5). Ninety-four percent of families shared knowledge from the game with others. Conclusions: Our pilot web-based family game first showed preliminary evidence on enhancing COVID-19 prevention knowledge and behaviors, and family well-being, with participants recognizing family strengths, reporting high satisfaction and various perceived benefits, and showing sustained gameplay. Trial Registration: The research protocol was registered at the National Institutes of Health (Identifier No. NCT04550065) on September 16, 2020.

Silencing of circ_0088036 inhibits growth and invasion of lung adenocarcinoma through miR-203/SP1 axis.

Lung cancer is the leading cause of cancer-related deaths worldwide. Circular RNA (circRNA) circ_0088036 is a recently discovered circRNA known for its roles in rheumatoid arthritis. The study aimed to study the function of circ_0088036 in lung adenocarcinoma (LUAD). Circ_0088036 expressions were analyzed in the Gene Expression Omnibus (GEO) database. The relationship between circ_0088036 expressions and clinicopathological data of LUAD was assessed. The messenger RNA and protein levels were analyzed by quantitative real-time polymerase chain reaction and Western blot. Cell viability, apoptosis, and invasion were tested by Cell Counting Kit-8, flow cytometry, and transwell assay. The direct interaction between microRNA-203 (miR-203) and circ_0088036 or specificity protein 1 (SP1) was confirmed by dual-luciferase reporter assay, RNA pull-down, and RNA immunoprecipitation assays. Circ_0088036 was overexpressed in LUAD from the analysis of the GEO database. The poor prognosis was found in the patients with high expressions of circ_0088036. The level of Circ_0088036 was increased in LUAD tissues and cells. In terms of function, the deletion of circ_0088036 inhibited LUAD tumorigenesis in vitro by repressing cell growth, invasion, and epithelial-mesenchymal transition (EMT). In mechanism, circ_0088036 could competitively sponge miR-203, thereby affecting the expressions of the target gene SP1. In addition, lessening of miR-203 and enlarging of SP1 could eliminate the anticancer effect of short hairpin RNA-circ_0088036 on LUAD cells. Besides, the knockout of circ_0088036 hindered the growth of xenografted tumors in vivo. Circ_0088036 promoted the LUAD cell growth, invasion, and EMT via modulating the miR-203/SP1 axis in LUAD.

Engineering APOBEC3A deaminase for highly accurate and efficient base editing.

Cytosine base editors (CBEs) are effective tools for introducing C-to-T base conversions, but their clinical applications are limited by off-target and bystander effects. Through structure-guided engineering of human APOBEC3A (A3A) deaminase, we developed highly accurate A3A-CBE (haA3A-CBE) variants that efficiently generate C-to-T conversion with a narrow editing window and near-background level of DNA and RNA off-target activity, irrespective of methylation status and sequence context. The engineered deaminase domains are compatible with PAM-relaxed SpCas9-NG variant, enabling accurate correction of pathogenic mutations in homopolymeric cytosine sites through flexible positioning of the single-guide RNAs. Dual adeno-associated virus delivery of one haA3A-CBE variant to a mouse model of tyrosinemia induced up to 58.1% editing in liver tissues with minimal bystander editing, which was further reduced through single dose of lipid nanoparticle-based messenger RNA delivery of haA3A-CBEs. These results highlight the tremendous promise of haA3A-CBEs for precise genome editing to treat human diseases.

Association between tobacco industry denormalisation beliefs and support for tobacco endgame policies: a population-based study in Hong Kong.

OBJECTIVES: To examine the associations between tobacco industry denormalisation (TID) beliefs and support for tobacco endgame policies. METHODS: A total of 2810 randomly selected adult respondents of population-based tobacco policy-related surveys (2018-2019) were included. TID beliefs (agree vs disagree/unsure) were measured by seven items: tobacco manufacturers ignore health, induce addiction, hide harm, spread false information, lure smoking, interfere with tobacco control policies and should be responsible for health problems. Score of each item was summed up and dichotomised (median=5, >5 strong beliefs; ≤5 weak beliefs). Support for tobacco endgame policies on total bans of tobacco sales (yes/no) and use (yes/no) was reported. Associations between TID beliefs and tobacco endgame policies support across various smoking status were analysed, adjusting for sociodemographics. RESULTS: Fewer smokers (23.3%) had strong beliefs of TID than ex-smokers (48.4%) and never smokers (48.5%) (p<0.001). Support for total bans on tobacco sales (74.6%) and use (76.9%) was lower in smokers (33.3% and 35.3%) than ex-smokers (74.3% and 77.9%) and never smokers (76.0% and 78.3%) (all p values<0.001). An increase in the number of TID beliefs supported was positively associated with support for a total ban on sales (adjusted risk ratio 1.06, 95% CI 1.05 to 1.08, p<0.001) and use (1.06, 95% CI 1.05 to 1.07, p<0.001). The corresponding associations were stronger in smokers than non-smokers (sales: 1.87 vs 1.25, p value for interaction=0.03; use: 1.78 vs 1.21, p value for interaction=0.03). CONCLUSION: Stronger TID belief was associated with greater support for total bans on tobacco sales and use. TID intervention may increase support for tobacco endgame, especially in current smokers.

DNAJA1­knockout alleviates heat stroke­induced endothelial barrier disruption via improving thermal tolerance and suppressing the MLCK­MLC signaling pathway.

Endothelial barrier disruption plays a key role in the pathophysiology of heat stroke (HS). Knockout of DNAJA1 (DNAJA1­KO) is thought to be protective against HS based on a genome­wide CRISPR­Cas9 screen experiment. The present study aimed to illustrate the function of DNAJA1­KO against HS in human umbilical vein endothelial cells. DNAJA1­KO cells were infected using a lentivirus to investigate the role of DNAJA1­KO in HS­induced endothelial barrier disruption. It was shown that DNAJA1­KO could ameliorate decreased cell viability and increased cell injury, according to the results of Cell Counting Kit­8 and lactate dehydrogenase assays. Moreover, HS­induced endothelial cell apoptosis was inhibited by DNAJA1­KO, as indicated by Annexin V­FITC/PI staining and cleaved­caspase­3 expression using flow cytometry and western blotting, respectively. Furthermore, the endothelial barrier function, as measured by transepithelial electrical resistance and FITC­Dextran, was sustained during HS. DNAJA1­KO was not found to have a significant effect on the expression and distribution of cell junction proteins under normal conditions without HS. However, DNAJA1­KO could effectively protect the HS­induced decrease in the expression and distribution of cell junction proteins, including zonula occludens­1, claudin­5, junctional adhesion molecule A and occludin. A total of 4,394 proteins were identified using proteomic analysis, of which 102 differentially expressed proteins (DEPs) were activated in HS­induced wild­type cells and inhibited by DNAJA1­KO. DEPs were investigated by enrichment analysis, which demonstrated significant enrichment in the 'calcium signaling pathway' and associations with vascular­barrier regulation. Furthermore, the 'myosin light­chain kinase (MLCK)­MLC signaling pathway' was proven to be activated by HS and inhibited by DNAJA1­KO, as expected. Moreover, DNAJA1­KO mice and a HS mouse model were established to demonstrate the protective effects on endothelial barrier in vivo. In conclusion, the results of the present study suggested that DNAJA1­KO alleviates HS­induced endothelial barrier disruption by improving thermal tolerance and suppressing the MLCK­MLC signaling pathway.

Preparation of type 3 rice resistant starch using high-pressure homogenous coenzyme treatment and investigating its potential therapeutic effects on blood glucose and intestinal flora in db/db mice.

Resistant starch from rice was prepared using high-pressure homogenization and branched chain amylase treatment. The yield, starch external structure, thermal properties, and crystal structure of rice-resistant starch prepared in different ways were investigated. The results showed that the optimum homogenizing pressure was 90 MPa, the optimum digestion time was 4 h, the optimum concentration of branched-chain amylase was 50 U/g and the yield of resistant starch was 38.58 %. Scanning electron microscopy results showed a rougher surface and more complete debranching of the homogenized coenzyme rice-resistant starch granules. FT-IR and X-ray diffraction results showed that the homogenization treatment exhibited a spiral downward trend on rice starch relative crystallinity and a spiral upward trend on starch debranching and recrystallization. The 4-week dietary intervention in db/db type 2 diabetic mice showed that homogeneous coenzyme rice-resistant starch had a better glycemic modulating effect than normal debranched starch and had a tendency to interfere with the index of liver damage in T2DM mice. Additionally, homogeneous coenzyme rice-resistant starch proved more effective in improving intestinal flora disorders and enhancing the abundance of probiotics in T2DM mice.

Pan-cancer image segmentation based on feature pyramids and Mask R-CNN framework.

BACKGROUND: Cancer, a disease with a high mortality rate, poses a great threat to patients' physical and mental health and can lead to huge medical costs and emotional damage. With the continuous development of artificial intelligence technologies, deep learning-based cancer image segmentation techniques are becoming increasingly important in cancer detection and accurate diagnosis. However, in segmentation tasks, there are differences in efficiency between large and small objects and limited segmentation effects on objects of individual sizes. The previous segmentation frameworks still have room for improvement in multi-scale collaboration when segmenting objects. PURPOSE: This paper proposes a method to train a deep learning segmentation framework using a feature pyramid processing dataset to improve the average precision (AP) index, and realizes multi-scale cooperation in target segmentation. OBJECTIVE: Pan-Cancer Histology Dataset for Nuclei Instance Segmentation and Classification (PanNuke) dataset was selected to include approximately 7500 pathology images with cells from 19 different types of tissues, including five classifications of cancer, non-cancer, inflammation, death, and connective tissue. METHODS: First, the method uses whole-slide images in the pan-cancer histology dataset for nuclei instance segmentation and classification (PanNuke) dataset, combined with the mask region convolutional neural network (Mask R-CNN) segmentation framework and improved loss function to segment and detect each cellular tissue in cancerous sections. Second, to address the problem of non-synergistic object segmentation at different scales in cancerous tissue segmentation, a scheme using feature pyramids to process the dataset was adopted as part of the feature extraction module. RESULTS: Extensive experimental results on this dataset show that the method in this paper yields 0.269 AP and a boost of about 4% compared to the original Mask R-CNN framework. CONCLUSIONS: It is effective and feasible to use feature pyramid to process data set to improve the effect of medical image segmentation.

Nurse-Led Brief Intervention for Enhancing Safe Sex Practice Among Emerging Adults in Hong Kong Using Instant Messaging: Feasibility Study.

BACKGROUND: The incidence of sexually transmitted infections has been increasing throughout the world. Additionally, substantial changes in emerging adults' attitudes toward sex and the popularization of premarital sex could further affect the diagnosis and treatment of sexually transmitted infections. With the high acceptability and effectiveness of instant messaging (IM) interventions for health promotion, there is potential for such interventions to improve condom use knowledge and promote safer sex practice. OBJECTIVE: The study evaluates the feasibility of a nurse-led IM intervention to promote safer sex practices in emerging adults. METHODS: A 30-minute adaptive IM intervention and a 5-day booster dose of daily messages after 2 weeks through WhatsApp (Meta Platforms, Inc) were conducted with emerging adults in local universities in Hong Kong aged between 18 and 29 years with previous sexual experience. A questionnaire was distributed 1 week after the intervention that measured the consistency in condom use, the change in condom use knowledge and attitudes, and the acceptability of the intervention. The feasibility of the intervention was assessed by Bowen's feasibility framework. RESULTS: A total of 20 participants completed the intervention and questionnaire. Results showed (1) high satisfaction level (mean satisfaction score: 9.10/10), (2) high demand of the intervention (retention rate: 95%), (3) smooth implementation of the intervention, (4) high practicality (13/20, 65% of the participants viewed IM to be an effective means of intervention), (5) potential integration of the intervention, and (6) significant mean increase in condom use knowledge and attitudes (mean increase 9.05; t19=3.727; 95% CI 3.97-14.13; P=.001). CONCLUSIONS: The IM intervention was feasible, acceptable, and had potential impacts on improving safer sex practices. These findings will support the future development of IM interventions in the arena of sexual health promotion.

Mechanism of organic phosphorus transformation and its impact on the primary production in a deep oligotrophic plateau lake during stratification.

Global warming is leading to extended stratification in deep lakes, which may exacerbate phosphorus (P) limitation in the upper waters. Conversion of labile dissolved organic P (DOP) is a possible adaptive strategy to maintain primary production. To test this, the spatiotemporal distributions of various soluble P fractions and phosphomonesterase (PME)/phosphodiesterase (PDE) activities were investigated in Lake Fuxian during the stratification period and the transition capacity of organic P and its impact on primary productivity were evaluated. The results indicated that the DOP concentration (mean 0.20 ± 0.05 µmol L-1) was significantly higher than that of dissolved inorganic P (DIP) (mean 0.08 ± 0.03 µmol L-1) in the epilimnion and metalimnion, which were predominantly composed of orthophosphate monoester (monoester-P) and orthophosphate diesters (diester-P). The low ratio of diester-P / monoester-P and high activities of PME and PDE indicate DOP mineralization in the epilimnion and metalimnion. We detected a DIP threshold of approximately 0.19 µmol L-1, corresponding to the highest total PME activity in the lake. Meta-analysis further demonstrated that DIP thresholds of PME activities were prevalent in oligotrophic (0.19 µmol L-1) and mesotrophic (0.74 µmol L-1) inland waters. In contrast to the phosphate-sensitive phosphatase PME, dissolved PDE was expressed independent of phosphate availability and its activity invariably correlated with chlorophyll a, suggesting the involvement of phytoplankton in DOP utilization. This study provides important field evidence for the DOP transformation processes and the strategy for maintaining primary productivity in P-deficient scenarios, which contributes to the understanding of P cycles and the mechanisms of system adaptation to future long-term P limitations in stratified waters.

Analysis of white matter tract integrity using diffusion kurtosis imaging reveals the correlation of white matter microstructural abnormalities with cognitive impairment in type 2 diabetes mellitus.

Background: This study aimed to identify disruptions in white matter integrity in type 2 diabetes mellitus (T2DM) patients by utilizing the white matter tract integrity (WMTI) model, which describes compartment-specific diffusivities in the intra- and extra-axonal spaces, and to investigate the relationship between WMTI metrics and clinical and cognitive measurements. Methods: A total of 73 patients with T2DM and 57 healthy controls (HCs) matched for age, sex, and education level were enrolled and underwent diffusional kurtosis imaging and cognitive assessments. Tract-based spatial statistics (TBSS) and atlas-based region of interest (ROI) analysis were performed to compare group differences in diffusional metrics, including fractional anisotropy (FA), mean diffusivity (MD), axonal water fraction (AWF), intra-axonal diffusivity (Daxon), axial extra-axonal space diffusivity (De,//), and radial extra-axonal space diffusivity (De,⊥) in multiple white matter (WM) regions. Relationships between diffusional metrics and clinical and cognitive functions were characterized. Results: In the TBSS analysis, the T2DM group exhibited decreased FA and AWF and increased MD, De,∥, and De,⊥ in widespread WM regions in comparison with the HC group, which involved 56.28%, 32.07%, 73.77%, 50.47%, and 75.96% of the mean WM skeleton, respectively (P < 0.05, TFCE-corrected). De,⊥ detected most of the WM changes, which were mainly located in the corpus callosum, internal capsule, external capsule, corona radiata, posterior thalamic radiations, sagittal stratum, cingulum (cingulate gyrus), fornix (stria terminalis), superior longitudinal fasciculus, and uniform fasciculus. Additionally, De,⊥ in the genu of the corpus callosum was significantly correlated with worse performance in TMT-A (ß = 0.433, P < 0.001) and a longer disease duration (ß = 0.438, P < 0.001). Conclusions: WMTI is more sensitive than diffusion tensor imaging in detecting T2DM-related WM microstructure abnormalities and can provide novel insights into the possible pathological changes underlying WM degeneration in T2DM. De,⊥ could be a potential imaging marker in monitoring disease progression in the brain and early intervention treatment for the cognitive impairment in T2DM.

Facial Physiological Characteristics and Skin Microbiomes Changes are Associated with Body Mass Index (BMI).

Background: Overweight and obesity have become public health problems worldwide. An increasing number of research works are focusing on skin physiology and the manifestations of obesity-associated skin diseases, but little is known about the correlations between body mass index (BMI), facial skin physiological parameters, and the facial skin microbiome in healthy women. Objective: To investigate the correlations between BMI, facial skin physiological parameters and facial bacteria and fungi in 198 women aged 18 to 35 years in Shanghai. Methods: According to the international BMI standard and Chinese reference standard, subjects were divided into three groups, "lean" B1, "normal" B2 and "overweight" B3, and the physiological parameters of facial skin were measured by non-invasive instrumental methods, and the skin microbiota was analyzed by 16S rRNA and ITS high-throughput sequencing. Results: Compared with the skin physiological parameters of the normal group, those of the overweight group exhibited a significant increase in trans-epidermal water loss (TEWL), which indicated that the skin barrier was impaired. The skin haemoglobin content was significantly increased, and skin surface pH was significant decreased in those with a high BMI. Furthermore, α-diversity, analysed using the Shannon, Chao, Sobs, and Ace indexes, was increased in the overweight group, suggesting that the diversity and species abundance of facial bacterial and fungal microbiota were also increased. Moreover, the overweight group had higher abundances of Streptococcus, Corynebacterium, Malassezia, and Candida. Notably, skin surface pH was significantly and negatively correlated with the relative abundances of Malassezia, Candida, and Cladosporium. Besides, the abundance of Malassezia was positively associated with the abundances of Staphylococcus and Corynebacterium. Conclusion: These results indicate that BMI is associated with differences in the biophysical properties and microbiome of the facial skin. A high BMI affects the integrity of skin barrier and changes the skin flora diversity and species composition.

Novel insights into Notch signaling in tumor immunity: potential targets for cancer immunotherapy.

Notch signaling pathway is a highly conserved system of cell-to-cell communication that participates in various biological processes, such as stem cell maintenance, cell fate decision, cell proliferation and death during homeostasis and development. Dysregulation of Notch signaling has been associated with many aspects of cancer biology, such as maintenance of cancer stem-like cells (CSCs), cancer cell metabolism, angiogenesis and tumor immunity. Particularly, Notch signaling can regulate antitumor or pro-tumor immune cells within the tumor microenvironment (TME). Currently, Notch signaling has drawn significant attention in the therapeutic development of cancer treatment. In this review, we focus on the role of Notch signaling pathway in remodeling tumor immune microenvironment. We describe the impact of Notch signaling on the efficacy of cancer immunotherapies. Furthermore, we summarize the results of relevant preclinical and clinical trials of Notch-targeted therapeutics and discuss the challenges in their clinical application in cancer therapy. An improved understanding of the involvement of Notch signaling in tumor immunity will open the door to new options in cancer immunotherapy treatment.

Sulfur defect-engineered Bi2S3-x/In2S3-y mediated signal enhancement of photoelectrochemical sensor for lead ions detection.

Lead ions (Pb2+) are heavy metal ions that are harmful to living organisms and ecosystems. It is important to realize sensitive detection of Pb2+ in the environment. In this study, a signal enhancement photoelectrochemical (PEC) sensor with high sensitivity was constructed for the detection of Pb2+. Firstly, to obtain excellent electron transfer performance, sulfur defect-engineered Bi2S3-x/In2S3-y mediated signal enhancement formed by Bi2S3 and In2S3 with well-matched structure in terms of energy level as the substrate materials. In this case, the introduction of sulfur vacancies further affects the electronic structure of the material, which significantly improves the electrical conductivity and effectively increases the electron transfer rate. In addition, the as-synthesized Cu@Cu2O nanosphere is chosen as the marker to accelerate the electron transfer through the surface plasmon resonance effect of Cu. The constructed sensor was able to detect Pb2+ in the range of 1 ng mL-1-100 µg mL-1 with a limit of detection of 19.2 pg mL-1. The sensor exhibits good reproducibility, specificity, and stability, indicating such PEC sensor can achieve the sensitive detection of Pb2+ in the environment. This work paves a new way for the construction of PEC sensors and the specific PEC detection of Pb2+ in environmental waters.