Dynamics of Bactrocera dorsalis Resistance to Seven Insecticides in South China.

Bactrocera dorsalis is a highly invasive and destructive pest distributed worldwide. Chemical insecticides remain the primary measure for their control; however, this species has already developed resistance to several insecticides. In recent years, there have been several reports of monitoring B. dorsalis resistance in China, but continuous monitoring results are lacking and do not even span a decade. In this study, we monitored the dynamics of resistance to seven insecticides among 11 geographically distinct Chinese populations of B. dorsalis (2010-2013; follow-up in 2023). The 11 populations were found to adapt rapidly to antibiotic insecticides (spinosad, emamectin benzoate, and avermectin), reaching high levels of insecticide resistance in several areas. Overall, a decreasing trend in resistance to organophosphorus insecticides (chlorpyrifos and trichlorfon) was observed, whereas pyrethroid (beta-cypermethrin and cyhalothrin) resistance trends were observed to both increase and decrease. The monitoring of field resistance among different B. dorsalis populations over the duration of this study is important for improving the efficiency and sustainability of agricultural pest management, and the results provide a scientific basis for the development of more effective resistance management strategies.

M2DC: A Meta-Learning Framework for Generalizable Diagnostic Classification of Major Depressive Disorder.

Psychiatric diseases are bringing heavy burdens for both individual health and social stability. The accurate and timely diagnosis of the diseases is essential for effective treatment and intervention. Thanks to the rapid development of brain imaging technology and machine learning algorithms, diagnostic classification of psychiatric diseases can be achieved based on brain images. However, due to divergences in scanning machines or parameters, the generalization capability of diagnostic classification models has always been an issue. We propose Meta-learning with Meta batch normalization and Distance Constraint (M2DC) for training diagnostic classification models. The framework can simulate the train-test domain shift situation and promote intra-class cohesion, as well as inter-class separation, which can lead to clearer classification margins and more generalizable models. To better encode dynamic brain graphs, we propose a concatenated spatiotemporal attention graph isomorphism network (CSTAGIN) as the backbone. The network is trained for the diagnostic classification of major depressive disorder (MDD) based on multi-site brain graphs. Extensive experiments on brain images from over 3261 subjects show that models trained by M2DC achieve the best performance on cross-site diagnostic classification tasks compared to various contemporary domain generalization methods and SOTA studies. The proposed M2DC is by far the first framework for multi-source closed-set domain generalizable training of diagnostic classification models for MDD and the trained models can be applied to reliable auxiliary diagnosis on novel data.

Multiple roles of arsenic compounds in phase separation and membraneless organelles formation determine their therapeutic efficacy in tumors.

Arsenic compounds are widely used for the therapeutic intervention of multiple diseases. Ancient pharmacologists discovered the medicinal utility of these highly toxic substances, and modern pharmacologists have further recognized the specific active ingredients in human diseases. In particular, Arsenic trioxide (ATO), as a main component, has therapeutic effects on various tumors (including leukemia, hepatocellular carcinoma, lung cancer, etc.). However, its toxicity limits its efficacy, and controlling the toxicity has been an important issue. Interestingly, recent evidence has pointed out the pivotal roles of arsenic compounds in phase separation and membraneless organelles formation, which may determine their toxicity and therapeutic efficacy. Here, we summarize the arsenic compounds-regulating phase separation and membraneless organelles formation. We further hypothesize their potential involvement in the therapy and toxicity of arsenic compounds, highlighting potential mechanisms underlying the clinical application of arsenic compounds.

Naringin and Naringenin: Potential Multi-Target Agents for Alzheimer's Disease.

Alzheimer's disease (AD) is one of the most common forms of neurodegenerative dementia. The etiology of AD is multifactorial, and its complex pathophysiology involves tau and amyloid-ß deposition, increased oxidative stress, neuroinflammation, metabolic disorders, and massive neuronal loss. Due to its complex pathology, no effective cure for AD has been found to date. Therefore, there is an unmet clinical need for the development of new drugs against AD. Natural products are known to be good sources of compounds with pharmacological activity and have potential for the development of new therapeutic agents. Naringin, a naturally occurring flavanone glycoside, is predominantly found in citrus fruits and Chinese medicinal herbs. Mounting evidence shows that naringin and its aglycone, naringenin, have direct neuroprotective effects on AD, such as anti-amyloidogenic, antioxidant, anti-acetylcholinesterase, and anti-neuroinflammatory effects, as well as metal chelation. Furthermore, they are known to improve disordered glucose/lipid metabolism, which is a high risk factor for AD. In this review, we summarize the latest data on the impact of naringin and naringenin on the molecular mechanisms involved in AD pathophysiology. Additionally, we provide an overview of the current clinical applications of naringin and naringenin. The novel delivery systems for naringin and naringenin, which can address their widespread pharmacokinetic limitations, are also discussed. The literature indicates that naringin and naringenin could be multilevel, multitargeted, and multifaceted for preventing and treating AD.

Enhancing spleen-targeted mRNA delivery with branched biodegradable tails in lipid nanoparticles.

The application of mRNA therapy is constrained by the current lipid nanoparticles' (LNPs) inability to target non-liver tissues. In this study, we demonstrate that ionizable lipids equipped with branched and biodegradable tails enhance the selective delivery of mRNA to the spleen, particularly to antigen-presenting cells. This approach offers novel insights into how the chemical structure of LNPs influences their organ-specific targeting capabilities.

Health outcomes of COVID-19 patients from Wuhan, China 3-year after hospital discharge: a cohort study.

OBJECTIVES: To evaluate changes in health outcomes between years 2 and 3 after discharge following COVID-19 and to identify risk factors for poor health 3-year post-discharge. DESIGN: This is a multicentre observational cohort study. SETTING: This study was conducted in two centres from Wuhan, China. PARTICIPANTS: Eligibility screening has been performed in 3988 discharged laboratory-confirmed adult COVID-19 patients. Exclusion criteria were refusal to participate, inability to contact and death before follow-up. The WHO COVID-19 guidelines on defining disease severity were adopted. RESULTS: 1594 patients participated in the 1-year, 2-year and 3-year follow-ups, including 796 (49.9%) male patients, and 422 (26.5%) patients were classified in the severe disease group. 3 years after discharge, 182 (11.4%) patients still complained of at least one symptom. The most common symptoms were fatigue, myalgia, chest tightness, cough, anxiety, shortness of breath and expectoration. Fatigue or myalgia, the most common symptom cluster, frequently coexisted with chest symptoms and anxiety. Symptom persistence between years 2 and 3 was reported in 70 patients (4.4%) for which intensive care unit (ICU) admission was a risk factor (p=0.038). Of the 1586 patients who completed the chronic obstructive pulmonary disease assessment test (CAT), 97 (6.1%) scored ≥10, with older age being associated with CAT ≥10 (p=0.007). CONCLUSIONS: Between years 2 and 3 after SARS-CoV-2 infection, most patients returned to an asymptomatic state, and only a few were still symptomatic. ICU admission was a risk factor for symptom persistence.

Gene expression and brain imaging association study reveals gene signatures in major depressive disorder.

Major depressive disorder is often characterized by changes in the structure and function of the brain, which are influenced by modifications in gene expression profiles. How the depression-related genes work together within the scope of time and space to cause pathological changes remains unclear. By integrating the brain-wide gene expression data and imaging data in major depressive disorder, we identified gene signatures of major depressive disorder and explored their temporal-spatial expression specificity, network properties, function annotations and sex differences systematically. Based on correlation analysis with permutation testing, we found 345 depression-related genes significantly correlated with functional and structural alteration of brain images in major depressive disorder and separated them by directional effects. The genes with negative effect for grey matter density and positive effect for functional indices are enriched in downregulated genes in the post-mortem brain samples of patients with depression and risk genes identified by genome-wide association studies than genes with positive effect for grey matter density and negative effect for functional indices and control genes, confirming their potential association with major depressive disorder. By introducing a parameter of dispersion measure on the gene expression data of developing human brains, we revealed higher spatial specificity and lower temporal specificity of depression-related genes than control genes. Meanwhile, we found depression-related genes tend to be more highly expressed in females than males, which may contribute to the difference in incidence rate between male and female patients. In general, we found the genes with negative effect have lower network degree, more specialized function, higher spatial specificity, lower temporal specificity and more sex differences than genes with positive effect, indicating they may play different roles in the occurrence and development of major depressive disorder. These findings can enhance the understanding of molecular mechanisms underlying major depressive disorder and help develop tailored diagnostic and treatment strategies for patients of depression of different sex.

[Incidence of comorbid ED with LUTS and its risk factors in patients with BPH].

OBJECTIVE: To investigate the incidence of comorbid ED with lower urinary tract symptoms (LUTS) and its risk factors in BPH patients. METHODS: Based on inclusion and exclusion criteria, we selected BPH patients visiting the outpatient department of the Second Xiangya Hospital of Central South University from January 2020 to January 2023. We collected the general and clinical data from the patients, including age, height, body weight, abdominal circumference, hip circumference, blood pressure, blood routine, liver function, kidney function, blood lipids and fasting blood glucose, obtained their IPSS, quality of life (QOL) scores, and IIEF-5 scores by questionnaire investigation, and performed data processing and analysis with the SPSS 22.0 software. RESULTS: The incidence rate of comorbid ED with LUTS in the BPH patients rose with the increase of age, 36.46% in the 45－49-year group, 43.72% in the 50－54-year group, 53.66% in the 55－59-year group, 69.23% in the 60－64-year group, and 78.74% in the 65－70-year group. The lipid accumulation product (LAP), visceral adiposity index (VAI), triglycerides and glucose (TyG), hepatic steatosis index (HSI), body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) were correlated positively with IPSS scores and negatively with IIEF-5 scores, while LDL-C and total cholesterol (TC) negatively with IPSS scores and positively with IIEF-5 scores. CONCLUSION: The incidence of comorbid ED with LUTS in BPH patients increases with age. The risk factors for this comorbidity include hypertension, dyslipidemia, diabetes, BMI, and lifestyle, and the risk of the condition can be effectively assessed by LAP, VAI, TYG, HSI, BMI, WHtR, WHR, TG and HDL-C.

Molecular mechanism and functional significance of Wapl interaction with the Cohesin complex.

The ring-shaped Cohesin complex, consisting of core subunits Smc1, Smc3, Scc1, and SA2 (or its paralog SA1), topologically entraps two duplicated sister DNA molecules to establish sister chromatid cohesion in S-phase. It remains largely elusive how the Cohesin release factor Wapl binds the Cohesin complex, thereby inducing Cohesin disassociation from mitotic chromosomes to allow proper resolution and separation of sister chromatids. Here, we show that Wapl uses two structural modules containing the FGF motif and the YNARHWN motif, respectively, to simultaneously bind distinct pockets in the extensive composite interface between Scc1 and SA2. Strikingly, only when both docking modules are mutated, Wapl completely loses the ability to bind the Scc1-SA2 interface and release Cohesin, leading to erroneous chromosome segregation in mitosis. Surprisingly, Sororin, which contains a conserved FGF motif and functions as a master antagonist of Wapl in S-phase and G2-phase, does not bind the Scc1-SA2 interface. Moreover, Sgo1, the major protector of Cohesin at mitotic centromeres, can only compete with the FGF motif but not the YNARHWN motif of Wapl for binding Scc1-SA2 interface. Our data uncover the molecular mechanism by which Wapl binds Cohesin to ensure precise chromosome segregation.

A hypothalamic-amygdala circuit underlying sexually dimorphic aggression.

Male animals often display higher levels of aggression than females. However, the neural circuitry mechanisms underlying this sexually dimorphic aggression remain elusive. Here, we identify a hypothalamic-amygdala circuit that mediates male-biased aggression in mice. Specifically, the ventrolateral part of the ventromedial hypothalamus (VMHvl), a sexually dimorphic region associated with eliciting male-biased aggression, projects densely to the posterior substantia innominata (pSI), an area that promotes similar levels of attack in both sexes of mice. Although the VMHvl innervates the pSI unidirectionally through both excitatory and inhibitory connections, it is the excitatory VMHvl-pSI projections that are strengthened in males to promote aggression, whereas the inhibitory connections that reduce aggressive behavior are strengthened in females. Consequently, the convergent hypothalamic input onto the pSI leads to heightened pSI activity in males, resulting in male-biased aggression. Our findings reveal a sexually distinct excitation-inhibition balance of a hypothalamic-amygdala circuit that underlies sexually dimorphic aggression.

An Overview on the Adhesion Mechanisms of Typical Aquatic Organisms and the Applications of Biomimetic Adhesives in Aquatic Environments.

Water molecules pose a significant obstacle to conventional adhesive materials. Nevertheless, some marine organisms can secrete bioadhesives with remarkable adhesion properties. For instance, mussels resist sea waves using byssal threads, sandcastle worms secrete sandcastle glue to construct shelters, and barnacles adhere to various surfaces using their barnacle cement. This work initially elucidates the process of underwater adhesion and the microstructure of bioadhesives in these three exemplary marine organisms. The formation of bioadhesive microstructures is intimately related to the aquatic environment. Subsequently, the adhesion mechanisms employed by mussel byssal threads, sandcastle glue, and barnacle cement are demonstrated at the molecular level. The comprehension of adhesion mechanisms has promoted various biomimetic adhesive systems: DOPA-based biomimetic adhesives inspired by the chemical composition of mussel byssal proteins; polyelectrolyte hydrogels enlightened by sandcastle glue and phase transitions; and novel biomimetic adhesives derived from the multiple interactions and nanofiber-like structures within barnacle cement. Underwater biomimetic adhesion continues to encounter multifaceted challenges despite notable advancements. Hence, this work examines the current challenges confronting underwater biomimetic adhesion in the last part, which provides novel perspectives and directions for future research.

GABRP inhibits the progression of oesophageal cancer by regulating CFTR: Integrating bioinformatics analysis and experimental validation.

Oesophageal cancer (EC) is a malignancy which accounts for a substantial number of cancer-related deaths worldwide. The molecular mechanisms underlying the pathogenesis of EC have not been fully elucidated. GSE17351 and GSE20347 data sets from the Gene Expression Omnibus (GEO) database were employed to screen differentially expressed genes (DEGs). Reverse transcription quantitative PCR (RT-qPCR) was used to examine hub gene expression. ECA-109 and TE-12 cells were transfected using the pcDNA3.1 expression vector encoding GABRP. The cell counting kit-8 (CCK-8), cell scratch and Transwell assays were performed to assess the effect of GABRP on EC cell proliferation, migration and invasion. Epithelial-mesenchymal transition (EMT)-associated protein levels were measured by Western blotting. Subsequently, CFTR was knocked down to verify whether GABRP affected biological events in EC cells by targeting CFTR. Seven hub genes were identified, including GABRP, FLG, ENAH, KLF4, CD24, ABLIM3 and ABLIM1, which all could be used as diagnostic biomarkers for EC. The RT-qPCR results indicated that the expression levels of GABRP, FLG, KLF4, CD24, ABLIM3 and ABLIM1 were downregulated, whereas the expression level of ENAH was upregulated. In vitro functional assays demonstrated that GABRP overexpression suppressed the proliferation, migration, invasion and EMT of EC cells. Mechanistically, GABRP promoted the expression of CFTR, and CFTR knockdown significantly counteracted the influence of GABRP overexpression on biological events in EC cells. Overexpression of GABRP inhibited EC progression by increasing CFTR expression, which might be a new target for EC treatment.

A prefrontal-habenular circuitry regulates social fear behaviour.

The medial prefrontal cortex (mPFC) has been implicated in the pathophysiology of social impairments including social fear. However, the precise subcortical partners that mediate mPFC dysfunction on social fear behaviour have not been identified. Employing a social fear conditioning paradigm, we induced robust social fear in mice and found that the lateral habenula (LHb) neurons and LHb-projecting mPFC neurons are synchronously activated during social fear expression. Moreover, optogenetic inhibition of the mPFC-LHb projection significantly reduced social fear responses. Importantly, consistent with animal studies, we observed an elevated prefrontal-habenular functional connectivity in subclinical individuals with higher social anxiety characterized by heightened social fear. These results unravel a crucial role of the prefrontal-habenular circuitry in social fear regulation and suggest that this pathway could serve as a potential target for the treatment of social fear symptom often observed in many psychiatric disorders.

POLR2J expression promotes glioblastoma malignancy by regulating oxidative stress and the STAT3 signaling pathway.

Glioblastoma is the most common cancer in the brain, resistant to conventional therapy and prone to recurrence. Therefore, it is crucial to explore novel therapeutics strategies for the treatment and prognosis of GBM. In this study, through analyzing online datasets, we elucidated the expression and prognostic value of POLR2J and its co-expressed genes in GBM patients. Functional experiments, including assays for cell apoptosis and cell migration, were used to explore the effects of POLR2J and vorinostat on the proliferation and migration of GBM cells. The highest overexpression of POLR2J, among all cancer types, was observed in GBM. Furthermore, high expression of POLR2J or its co-expressed genes predicted a poor outcome in GBM patients. DNA replication pathways were significantly enriched in the GBM clinical samples with high POLR2J expression, and POLR2J suppression inhibited proliferation and triggered cell cycle G1/S phase arrest in GBM cells. Moreover, POLR2J silencing activated the unfolded protein response (UPR) and significantly enhanced the anti-GBM activity of vorinostat by suppressing cell proliferation and inducing apoptosis. Additionally, POLR2J could interact with STAT3 to promote the metastatic potential of GBM cells. Our study identifies POLR2J as a novel oncogene in GBM progression and provides a promising strategy for the chemotherapeutic treatment of GBM.

IGF-1's protective effect on OSAS rats' learning and memory.

PURPOSE: Patients with obstructive sleep apnea syndrome (OSAS) frequently experience cognitive dysfunction, which may be connected to chronic intermittent hypoxia (CIH). Insulin-like growth factor-1 (IGF-1) is thought to be closely associated with cognitive function, but its role in cognitive impairment caused by OSAS is unclear. The purpose of this study was to investigate the potential protective effect of IGF-1 on cognitive impairment in OSAS rats. METHODS: Healthy male SD rats (n = 40) were randomly assigned into four groups: control group, CIH group, NS + CIH group, and IGF-1 + CIH group. All experimental rats except for those in the control group were exposed to intermittent hypoxic (IH) environments for 8 h per day over 28 days. Prior to daily exposure to IH, rats in the IGF-1 + CIH group received subcutaneous injections of IGF-1. The Morris water maze test was conducted on all experimental rats. Brain tissue testing methods included Enzyme-Linked Immunosorbent Assay, Hematoxylin and eosin staining, Immunohistochemistry, and Western blotting. RESULTS: The rat model of OSAS was successfully established following exposure to CIH and exhibited significant cognitive impairment. However, daily subcutaneous injections of IGF-1 partially restored the impaired cognitive function in OSAS rats. Compared with the control group, there was a significant decrease in the expression levels of IGF-1, p-IGF-IR, and SYP in the CIH group; however, these expression levels increased significantly in the IGF-I + CIH group. CONCLUSION: In OSAS rats, IGF-1 enhances learning memory; this effect may be linked to increased p-IGF-1R and SYP protein production in the hippocampus.

Self-care behaviours of first-generation Chinese immigrants living with cardiovascular disease: A qualitative study.

AIM: To identify and describe self-care behaviours performed by Chinese immigrants living with cardiovascular disease in Australia, and factors perceived as barriers and facilitators to evidence-based cardiac self-care. DESIGN: A qualitative descriptive design. METHODS: Individual semi-structured phone interviews were conducted among participants meeting the following criteria: (1) first-generation Chinese immigrants to Australia, born in Mainland China, Hong Kong, Macao or Taiwan; (2) Australian permanent residents or citizens; (3) self-reported or medically diagnosed with coronary heart disease, stroke or heart failure; (4) able to speak English or Mandarin; (5) able to provide informed consent, excluding those with history or evidence of impaired cognition such as dementia. Participants were recruited via social media, Chinese community associations and medical centres from September 2021 to June 2022. Data were analysed using inductive and deductive thematic analysis, guided by the Middle-Range Theory of Self-Care of Chronic Illness. The study was reported in line with the COREQ checklist. RESULTS: Twenty participants were interviewed, 60% female, mean age 69.9 years. Most migrated to Australia at older age following their retirement in China; most had limited English proficiency. Many practiced adequate self-care for their CVD in self-care maintenance and monitoring. Variously, they adopted heart-healthy diets, developed exercise routines, attended medical services and closely monitored their body signs and symptoms. However, self-adjusting medications, taking Traditional Chinese Medicine and self-administering health supplements were prevalent practices and first-response management of acute cardiac symptoms was suboptimal. Linguistic and cultural barriers to obtaining mainstream heart health information meant most participants resorted to informal, anecdotal and mainland Chinese sources. CONCLUSION: Diverse factors were held responsible for sub-optimal self-care behaviours but lack of access to linguistically and culturally appropriate heart health information was widely blamed. Linguistically and culturally appropriate community-based heart health education programmes are urgently needed, targeting healthy lifestyle modification, medication literacy and cardiac symptom management. IMPACT: Study findings can be used to improve cardiac nurses' cultural sensitivity and practices targeting Chinese immigrants. Partnering with Chinese community associations offers health service providers and policymakers an innovative route to co-design and deliver targeted heart health education interventions and support for this population. PUBLIC CONTRIBUTION: Chinese community centre managers contributed to data collection by supporting participant recruitment.

Individual and group behavioral responses to nutritional state and context in a social fish.

Understanding how animal collectives and societies form and function is a fundamental goal in animal biology. To date, research examining fish shoaling behavior has focused mostly on the general principles and ecological relevance of the phenomeon, while the ways in which physiological state (e.g., nutrition) affects collective behavior remain overlooked. Here, we investigated the shoaling behavior of common minnows (Phoxinus phoxinus) with three different nutritional states (control treatment: fasting for 24 h, fasting treatment: fasting for 7 days, and digestion treatment: 1 h after satiation feeding) across two ecological contexts (i.e., without and with food). No effects of either nutritional state or context were found on swimming speed, but the acceleration was greater in the digestion group than in the control group, with that in the fasting group being intermediate. Similar to change tendency in group length and group width of shoals, both interindividual distance and nearest neighbor distance were also greater in the fasting group than in the digestion group, suggesting that fasting and digestion may exert opposite driving forces on group cohesion. However, neither nutritional state nor context influenced the group area, group speed, group percent time moving, or group polarization. Both the foraging efficiency and the percentage of food items consumed by the fish shoals were greater in the fasting and control groups than in the digestion group. Our study suggested that one week of hunger and the energetically demanding stage of food digestion tend to have opposite influences on group shape, while the social foraging context does not influence the individual and group behavior of fish.