Unveiling the hidden pathways: Exploring astrocytes as a key target for depression therapy.

Depressive disorders are widely debilitating psychiatric disease. Despite the considerable progress in the field of depression therapy, extensive research spanning many decades has failed to uncover pathogenic pathways that might aid in the creation of long-acting and rapid-acting antidepressants. Consequently, it is imperative to reconsider existing approaches and explore other targets to improve this area of study. In contemporary times, several scholarly investigations have unveiled that persons who have received a diagnosis of depression, as well as animal models employed to study depression, demonstrate a decrease in both the quantity as well as density of astrocytes, accompanied by alterations in gene expression and morphological attributes. Astrocytes rely on a diverse array of channels and receptors to facilitate their neurotransmitter transmission inside tripartite synapses. This study aimed to investigate the potential processes behind the development of depression, specifically focusing on astrocyte-associated neuroinflammation and the involvement of several molecular components such as connexin 43, potassium channel Kir4.1, aquaporin 4, glutamatergic aspartic acid transporter protein, SLC1A2 or GLT-1, glucocorticoid receptors, 5-hydroxytryptamine receptor 2B, and autophagy, that localized on the surface of astrocytes. The study also explores novel approaches in the treatment of depression, with a focus on astrocytes, offering innovative perspectives on potential antidepressant medications.

Altered spontaneous neurological activity in methamphetamine use disorders and its association with cognitive function.

BACKGROUND: Methamphetamine (MA) is a widely used and detrimental drug, yet the precise mechanisms by which MA affects cognitive function remain unclear. This study aims to investigate the relationship between cognitive function and brain functional imaging in individuals with MA use disorder (MUD). METHODS: This study involved 45 patients diagnosed with MUD and 43 healthy controls (HC). Cognitive function assessment utilized the MATRICS Consensus Cognitive Battery, and functional data were acquired using a 3.0 Tesla magnetic resonance imaging scanner. RESULTS: The MUD group exhibited lower regional homogeneity (ReHo) values in the bilateral postcentral, the left superior temporal, and the left lingual regions compared to the HC group. Additionally, the MUD group displayed higher amplitude of low-frequency fluctuation (ALFF) values in the bilateral fusiform and the left putamen compared to the HC group, along with lower ALFF values in the bilateral postcentral cortices and the left middle cingulate cortex compared to the HC group (all p < 0.05, with false discovery rate corrected). Linear regression analysis revealed a positive correlation between the ReHo value in the right postcentral cortex and the neuropsychology assessment battery-mazes test (p = 0.014). Furthermore, the ALFF value in the left putamen showed negative correlations with the scores of the digit-symbol coding test (p = 0.027), continuous performance test (p = 0.037), and battery-mazes test (p = 0.024). CONCLUSION: Patients with MUD exhibit altered brain spontaneous neurological activities, and the intensity of spontaneous neurological activity in the left putamen is strongly associated with cognitive function.

The Effect of Sex on the Therapeutic Efficiency of Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis Based on Randomized Controlled Trials.

BACKGROUND: Sex is an important factor influencing the immune system, and the distribution of tumors, including their types and subtypes, is characterized by sexual dichotomy. The aim of this study was to investigate whether there is an association between sex and the treatment effect of immune checkpoint inhibitors (ICI). METHODS: Four bibliographic databases were searched. Studies of randomized controlled trials (RCTs) assessing the efficacy of ICI were identified and used, and the primary endpoint was the difference in efficacy of ICI between males and females, presented as overall survival (OS), progression-free survival (PFS) and recurrence-free survival (RFS). The study calculated the pooled HRs and 95% CIs for OS, PFS and RFS for males and females using a random effects model or a fixed effects model, and thereby assessed the effect of sex on the efficacy of ICI treatment. This study is registered with PROSPERO (CRD42022370939). RESULTS: A total of 103 articles, including a total of 63,755 patients with cancer, were retrieved from the bibliographic database, of which approximately 70% were males. In studies with OS as the outcome, the combined hazard ratio (HR) was 0.77 (95% CI 0.74-0.79) for male patients treated with ICI and 0.81 (95% CI 0.78-0.85) for female patients compared to controls, respectively. The difference in efficacy between males and females was significant. CONCLUSIONS: ICI therapy, under suitable conditions for its use, has a positive impact on survival in various types of tumors, and male patients benefit more than females. It may be necessary to develop different tumor immunotherapy strategies for patients of different sexes.

Unveiling the Association between HPV and Pan-Cancers: A Bidirectional Two-Sample Mendelian Randomization Study.

INTRODUCTION: More and more studies have focused on the associations between human papillomavirus (HPV) infection and pan-cancers. However, current evidence is largely based on retrospective studies, which are susceptible to confounding factors and do not enable the establishment of causal relationships. METHODS: A bidirectional two-sample Mendelian randomization (MR) design was employed to thoroughly evaluate the causal relationships between HPV and 12 site-specific cancers except cervical cancer. Single nucleoside polymers (SNPs) with strong evidence from genome-wide association studies (GWAS) were selected from HPV exposure datasets and used as instrumental variables (IVs) in this study. For the MR analysis results, MR-Egger's intercept P test, MR-PRESSO global test, Cochran's Q test and a leave-one-out test were applied for sensitivity analysis. Using HPVTIMER, we also performed immune infiltration analyses in head and neck squamous cell carcinoma (HNSCC), oropharyngeal squamous cell carcinoma (OPSCC) and vulval squamous cell carcinoma (VSCC) to evaluate the tumor-immune microenvironment. RESULTS: Based on the evidence of MR analysis, our study conclusively identified HPV16 as a risk factor implicated in the development of bladder cancer, colorectal cancer, and breast cancer, while HPV18 was identified as a risk factor for prostate cancer, ovarian cancer, lung cancer and breast cancer. The MR results also showed that HPV16 may be a protective factor for prostate cancer, anal cancer, lung cancer and oropharyngeal cancer, while HPV18 may be a protective factor for vaginal cancer. CONCLUSION: An HPV infection may modulate the immune microenvironment and therefore has a potential inhibitory effect on the development of certain cancers. These conclusions provided new insights into the potential mechanisms of carcinogenesis and needed further research for validation.

Completely Free from PAM Limitations: Asymmetric RPA with CRISPR/Cas12a for Nucleic Acid Assays.

Experimentally, Cas12a can recognize multiple protospacer adjacent motif (PAM) sequences and is not restricted to the "TTTN". However, the application of the CRISPR/Cas12a system is still limited by the PAM for double-stranded DNA (dsDNA). Here, we developed asymmetric RPA (Asy-RPA) to completely break the limitations of PAM. Asy-RPA not only achieved efficient amplification but also converted dsDNA to single-stranded DNA (ssDNA) without complicated steps. The ssDNA products activated the trans-cleavage activity of Cas12a, outputting signals. The application of Asy-RPA completely freed Cas12a from the PAM, which can be more widely used in nucleic acid detection, such as lumpy skin disease virus, with an actual detection limit as low as 1.21 × 101 copies·µL-1. More importantly, Cas12a was intolerant to mutations on ssDNA. This provided technical support for the detection and identification of wild-type Mycobacterium tuberculosis (WT-TB) and rifampin-resistant mutant-type M. tuberculosis (MT-TB). The detection limit was as low as 1 fM for 1% mixed samples. The detection and availability of different treatment options for treatment-resistant and WT-TB were significant for the elimination of TB. In summary, the platform consisting of Asy-RPA and CRISPR/Cas12a was suitable for the detection of various viruses and bacteria and was a boon for the detection of dsDNA without recognizable PAM.

Improving the Anti-washout Property of Acrylate Grouting Material by Bentonite: Its Characterization, Improving Mechanism, and Practical Application.

Acrylate is a popular polymer grouting material that has been widely used to control groundwater seepage. However, the vulnerability of acrylate slurry to dynamic water washout restricts its application in groundwater environments characterized by high flow velocity and water pressures. In this paper, lithium bentonite (Li-B) was used to modify the traditional magnesium acrylate (AC) grouting material. The influence of Li-B to AC ratios on the modified materials' washout resistance was explored, and the modification mechanism was analyzed using X-ray diffraction (XRD), infrared spectroscopy (IR), and scanning electron microscopy (SEM). Finally, the anti-washout ability of the modified slurry was verified through engineering applications. Results revealed that LiB-AC grout had adjustable setting times (10.5 to 395.6 s), minimal bleeding (0.1%), higher viscosity (65 mPa·s) and expansibility (350%), stronger anti-water dispersibility (24 times that of pure AC slurry), higher mechanical strength (compressive strength is 0.386 MPa, tensile strength is 0.088 MPa), and better impermeability (2.23 × 10-8 m/s). The lithium bentonite was beneficial to the setting time, bleeding, viscosity, slurry retention rate, impermeability, and mechanical strength of the acrylate grout. However, it diminished the expansibility of the acrylate grout. At the optimal acrylate content (20%), the mechanical strength and impermeability of the LiB-AC grout were the highest. The better performance of LiB-AC grout was attributed to the formation of a more stable and dense interlaced spatial network structure after the modification by Li-B. The LiB-AC grout was used in the dynamic water grouting project of a metro shield tunnel segment and achieved better anti-washout performance than cement-water glass and pure AC slurry.

Field-friendly and ultra-fast detection platform without nucleic acid extraction for virus detection.

The polymeric chain reaction (PCR) has come under fire for being time-consuming, requiring expensive equipments, and requiring the extraction and purification of nucleic acids. Here, an ultra-fast and sensitive detection platform without nucleic acid extraction solved the above problems. Firstly, the RoomTemp Sample Lysis Kit released the nucleic acid in 3 min and removed the inhibition to facilitate the amplification reaction. What's more, ultra-fast PCR (UF-PCR) can complete 40 cycles in just 15 min and 50 s. To improve the sensitivity and provide more convenient reading modes, CRISPR/Cas12a was mediated to detect Lumpy skin disease virus (LSDV). The platform output fluorescence and Lateral flow dipstick (LFD) signals. The actual detection limit was 2 × 101 copies·µL-1. The portable platform realized visualization, excellent sensitivity and quick speed. In summary, the field-friendly testing platform had great potential in practical testing.

Paternal cadmium exposure affects estradiol synthesis by impairing intracellular cholesterol homeostasis and mitochondrial function in offspring female mice.

Cadmium (Cd) is a toxic heavy metal commonly found in nature and an endocrine disrupting chemical (EDC). Previous studies found that Cd can damage several organs, including the kidneys, bones, cardiovascular system and reproductive system. However, the effect of paternal Cd exposure on the offspring is unclear. In this study, 1 mg/kg of cadmium chloride (CdCl2) was injected intraperitoneally every other day in 8-week-old C57BL/6 J male mice to study the effects on their female offspring. Our results showed an increase in body weight, water intake and food intake in F1 female mice from the Cd-exposed group. The development of secondary follicles and antral follicles in the ovaries of Cd-treated was inhibited. Serum estradiol (E2) was found to be decreased. Further analysis revealed significant downregulation of StAR, P450scc, 17ß-HSD, CYP17A1 and CYP19A1, which are related to E2 synthesis. Serum total cholesterol was increased and free cholesterol was reduced. Total cholesterol in ovarian tissue was decreased. qRT-PCR and Western blot analysis revealed a decrease in the mRNA and protein expression of HMGCR, LDLR, and ABCA1, which are associated with cholesterol homeostasis. Oil red O staining indicated that lipid droplets (LDs) were accumulated in ovarian tissues, while the expression of ATGL and HSL proteins associated with lipid droplet degradation was significantly downregulated. In juvenile female mice, ultrastructural alterations of mitochondria in the ovaries were observed by transmission electron microscopy (TEM). In adult female mice, the expression of proteins associated with mitochondrial dynamics (DRP1 and MFN2) was significantly reduced in the ovaries. Overall, our study suggests that paternal Cd exposure inhibits follicular development, and affects serum E2 synthesis by impairing cholesterol homeostasis and affecting mitochondrial function.

Suicidal ideation in Chinese patients with chronic schizophrenia: prevalence, clinical correlates, and relationship with alexithymia.

Suicidal ideation (SI) is common among people with schizophrenia. However, it has received less attention than suicide attempts (SA), especially in the Chinese population. Alexithymia is a well-established risk factor for SI across different populations. Nevertheless, very few studies evaluated their relationship in schizophrenia patients. We aimed to determine the prevalence and clinical correlates of SI and its relationship with alexithymia in 812 Chinese chronic schizophrenia inpatients. We assessed SI, clinical symptoms, and alexithymia by the Beck Scale for Suicidal Ideation, the Positive and Negative Syndrome Scale (PANSS), and the Toronto Alexithymia Scale, respectively. A multiple logistic regression model was conducted to identify independent correlates of SI. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were performed to determine the ability of our model to distinguish between patients with and without SI. 10% (n = 84) reported current SI. Lifetime SA (OR, 4.68; 95% CI 2.76-7.94, p < 0.001), PANSS depressive factor (OR, 1.24; 95% CI 1.12-1.38, p < 0.001), PANSS positive subscale (OR, 1.055; 95% CI 1.004-1.108, p = 0.035), and difficulty identifying emotions (OR, 1.07; 95% CI 1.03-1.12, p = 0.002) were associated with SI. The AUC value was 0.80, indicating excellent distinguishing capabilities. Timely assessments of these factors may help identify schizophrenia patients who are at risk for SI.

IRAK-M Ablation Promotes Status Epilepticus-Induced Neuroinflammation via Activating M1 Microglia and Impairing Excitatory Synaptic Function.

Epilepsy is one of the most common neurological disorders. The pro-epileptic and antiepileptic roles of microglia have recently garnered significant attention. Interleukin-1 receptor-associated kinase (IRAK)-M, an important kinase in the innate immune response, is mainly expressed in microglia and acts as a negative regulator of the TLR4 signaling pathway that mediates the anti-inflammatory effect. However, whether IRAK-M exerts a protective role in epileptogenesis as well as the molecular and cellular mechanisms underlying these processes are yet to be elucidated. An epilepsy mouse model induced by pilocarpine was used in this study. Real-time quantitative polymerase chain reaction and western blot analysis were used to analyze mRNA and protein expression levels, respectively. Whole-cell voltage-clamp recordings were employed to evaluate the glutamatergic synaptic transmission in hippocampal neurons. Immunofluorescence was utilized to show the glial cell activation and neuronal loss. Furthermore, the proportion of microglia was analyzed using flow cytometry. Seizure dynamics influenced the expression of IRAK-M. Its knockout dramatically exacerbated the seizures and the pathology in epilepsy and increased the N-methyl-d-aspartate receptor (NMDAR) expression, thereby enhancing glutamatergic synaptic transmission in hippocampal CA1 pyramidal neurons in mice. Furthermore, IRAK-M deficiency augmented hippocampal neuronal loss via a possible mechanism of NMDAR-mediated excitotoxicity. IRAK-M deletion promotes microglia toward the M1 phenotype, which resulted in high levels of proinflammatory cytokines and was accompanied by a visible increase in the expressions of key microglial polarization-related proteins, including p-STAT1, TRAF6, and SOCS1. The findings demonstrate that IRAK-M dysfunction contributes to the progression of epilepsy by increasing M1 microglial polarization and glutamatergic synaptic transmission. This is possibly related to NMDARs, particularly Grin2A and Grin2B, which suggests that IRAK-M could serve as a novel therapeutic target for the direct alleviation of epilepsy.

The End of the Gray Zone: One-Tube Nested Recombinase Polymerase Amplification with Ultrahigh Signal-to-Noise Ratio for Precisely Detecting and Surveilling Viruses.

The samples were difficult to accurately determine positive or negative between 35 and 40 cycles by real-time quantitative PCR (qPCR) as the standard method. Here, we developed one-tube nested recombinase polymerase amplification (ONRPA) technology with CRISPR/Cas12a to overcome this difficulty. ONRPA broke the amplification plateau to substantially enhance the signals, which considerably improved the sensitivity and eliminated the problem of gray area. Using two pairs of primers one after another, it improved precision by lowering the probability of magnifying several target zones, which was completely free of contamination by nonspecific amplification. This was important in nucleic acid testing. Finally, by the CRISPR/Cas12a system as a terminal output, the approach achieved a high signal output as few as 2.169 copies·µL-1 in 32 min. ONRPA was 100-fold more sensitive than conventional RPA and 1000-fold compared to qPCR. ONRPA coupled with CRISPR/Cas12a will be an important and new promoter of RPA in clinical applications.

Multiple accurate and sensitive arrays for Capripoxvirus (CaPV) differentiation.

Capripoxvirus (CaPV) contains three viruses that have caused massive losses in the livestock and dairy industries. Accurate CaPV differentiation has far-reaching implications for effectively controlling outbreaks. However, it has a great challenge to distinguishing three viruses due to high homology of 97%. Here, we established a sensitive CRISPR/Cas12a array based on Multiple-recombinase polymerase amplification (M-RPA) for CaPV differentiation, which provided a more comprehensive and accurate differentiation mode targeting VARV B22R and RPO30 genes. By sensitive CRISPR/Cas12a and M-RPA, the actual detection limits of three viruses were as low as 50, 40 and 60 copies, respectively. Moreover, Lateral flow dipstick (LFD) array based on CRISPR/Cas12a achieved portable and intuitive detection, making it suitable for point-of-care testing. Therefore, CRISPR/Cas12a array and LFD array paved the way for CaPV differentiation in practice. Additionally, we constructed a real-time quantitative PCR (qPCR) array to fill the qPCR technical gap in differentiation and to facilitate the quarantine departments.

Optimized Method Based on Subspace Merging for Spectral Reflectance Recovery.

The similarity between samples is an important factor for spectral reflectance recovery. The current way of selecting samples after dividing dataset does not take subspace merging into account. An optimized method based on subspace merging for spectral recovery is proposed from single RGB trichromatic values in this paper. Each training sample is equivalent to a separate subspace, and the subspaces are merged according to the Euclidean distance. The merged center point for each subspace is obtained through many iterations, and subspace tracking is used to determine the subspace where each testing sample is located for spectral recovery. After obtaining the center points, these center points are not the actual points in the training samples. The nearest distance principle is used to replace the center points with the point in the training samples, which is the process of representative sample selection. Finally, these representative samples are used for spectral recovery. The effectiveness of the proposed method is tested by comparing it with the existing methods under different illuminants and cameras. Through the experiments, the results show that the proposed method not only shows good results in terms of spectral and colorimetric accuracy, but also in the selection representative samples.

Four-ray interference model for complete characterization of tubular anti-resonant hollow-core fibers.

We propose a comprehensive four-ray interference model based on simple geometric optics that can be employed to characterize all the structural parameters of an anti-resonant hollow-core fiber with tubular cladding structures in a non-invasive and fast way. Combining this model with white-light side-scattering spectroscopy, the outer and the inner radii of the jacket tube can be measured with sub-micron accuracy. The improved illumination source and collimator enable fast spectrum acquisition and identification of the key interference peaks of the four rays. A fitting-based estimate of the interference peaks fully exploits a wealth of spectra acquired at different rotation angles and can help to retrieve the diameter of the cladding tubes with high resolution of 0.17 µm, which exceeds the diffraction limit of the probe light. We also report for the first time, to the best of our knowledge, the polarization and the transverse mode dependences in the side-scattering interference spectra, with which the glass wall thicknesses of the cladding tubes can be estimated on the basis of our four-ray interference model as well.

Optimized clustering method for spectral reflectance recovery.

An optimized method based on dynamic partitional clustering was proposed for the recovery of spectral reflectance from camera response values. The proposed method produced dynamic clustering subspaces using a combination of dynamic and static clustering, which determined each testing sample as a priori clustering center to obtain the clustering subspace by competition. The Euclidean distance weighted and polynomial expansion models in the clustering subspace were adaptively applied to improve the accuracy of spectral recovery. The experimental results demonstrated that the proposed method outperformed existing methods in spectral and colorimetric accuracy and presented the effectiveness and robustness of spectral recovery accuracy under different color spaces.

Operational efficiency evaluation of urban and rural residents' basic pension insurance system by utilizing a picture fuzzy TOPSIS method based on the cumulative prospect theory.

Population aging is the most serious challenge facing the pension insurance system in China in the next few decades. Compared with the employees of civil servants and enterprises and institutions, urban and rural residents are unstable vulnerable groups with less income. In order to deal with the pension risks caused by the growing aging population and solve the security problems of urban and rural residents, our government has carried out a series of constructive works in the pension insurance system: in view of the rural and urban residents, new rural social endowment insurance system and the social endowment insurance system for urban residents have been set up and combined into a unified basic old-age insurance system for urban and rural residents in 2014. With the continuous expansion in the scale of income and expenditure of urban and rural living insurance funds and the size of the insured number, it is of great necessity to evaluate the efficiency of this system. The operational efficiency evaluation of urban and rural residents' basic pension insurance systems is viewed as multi-attribute group decision-making (MAGDM). In this paper, we propose an approach by combining the traditional Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS) with cumulative prospect theory (CPT) which can be widely used with vague information. Thus, the main contribution of this study is as follows: (1) the TOPSIS method is extended by picture fuzzy sets (PFSs) with unknown weight information; (2) entropy method to obtain the original weights of attributes; (3) the picture fuzzy-CPT-TOPSIS (PF-CPT-TOPSIS) method is used to deal with the MAGDM problems under PFSs; (4) a numerical instance for operational efficiency evaluation of urban and rural residents' basic pension insurance systems is proposed to testify the effectiveness of new method; and (5) some comparative studies are provided to give effect to the rationality of PF-CPT-TOPSIS approach.

Carbon nanodots combined with loop-mediated isothermal amplification (LAMP) for detection of African swine fever virus (ASFV).

The spread of African swine fever virus (ASFV) caused huge economic costs, so early detection is particularly important. Here, we established a fluorescence biosensor based on carbon nanodots (CNDs) and loop-mediated isothermal amplification (LAMP) to ultra-sensitively detect ASFV. LAMP with high efficiency produced a large amount of pyro phosphoric acid and caused pH change in a short time. CNDs with strong light stability had a large fluorescence response at the emission wavelength of 585.5 nm to small pH change by the excitation wavelength of 550 nm. The biosensor realized "turn-off-on" mode for ASFV detection with the detection limit as low as 15.21 copies µL-1. In addition, the biosensor had high accuracy in the actual sample assay. Therefore, the biosensor achieved rapid, sensitive, low-cost, and simple detection for ASFV. Moreover, the biosensor broadened the detection pathway of LAMP as a tool with great development prospect.

Factors Associated With the Vaccination Behavior Among COVID-19 Vaccine Hesitant College Students in Wuhan, China: A Survey Based on Social Psychological Dimension.

Background: During the COVID-19 pandemic, vaccine hesitancy (VH) on COVID-19 vaccination still exists in different populations, which has a negative impact on epidemic prevention and control. The objectives were to explore college students' willingness to vaccinate, determine the factors influencing the vaccination behavior of students with COVID-19 vaccine hesitancy, and provide a basis for improving the compliance of college students with COVID-19 vaccination. Methods: The universities in Wuhan are categorized into three levels according to their comprehensive strength and randomly sampled at each level, of which ten universities were selected. A self-designed anonymous electronic questionnaire was distributed online from May 12 to 31, 2021 to investigate the hesitancy, vaccination status, and influencing factors of COVID-19 vaccination among college students in Wuhan. Results: Of the 1,617 participants (1,825 students received the electronic questionnaire) surveyed, 19.0% reported COVID-19 vaccine hesitancy. Among the vaccine-hesitant students, 40.1% were vaccinated against COVID-19. The binary logistic regression analysis shows that families' attitudes "Uncertain" (odds ratio (OR) = 0.258 [0.132-0.503]), vaccination risk psychology (OR = 0.242 [0.079-0.747]) and wait-and-see mentality (OR = 0.171 [0.068-0.468]) are negative factors for the vaccination behavior of hesitant students, while herd mentality (OR = 7.512 [2.718-20.767]) and uncertainty of free policy's impact on vaccine trust (OR = 3.412 [1.547-7.527]) are positive factors. Conclusion: The vaccine hesitancy among college students in Wuhan was relatively high. Family support, herd mentality and free vaccination strategies can help improve vaccination among hesitant students, while vaccination risk psychology and "wait-and-see" psychology reduce the possibility of vaccination. The vaccination strategy of college students should be strengthened from the perspective of social psychological construction.