Dorsomedial striatal AMPA receptor antagonism increases alcohol binge drinking in selectively bred crossed high alcohol preferring mice.

Crossed high alcohol preferring (cHAP) mice have been selectively bred to consume considerable amounts of alcohol resulting in binge drinking. The dorsomedial striatum (DMS) is a brain region involved in goal-directed action selection, and dorsolateral striatum (DLS) is a brain region involved in habitual action selection. Alcohol use disorder (AUD) may involve a disruption in the balance between the DMS and DLS. While the DLS is involved in binge drinking, the reliance on the DMS and DLS in binge drinking has not been investigated in cHAP mice. We have previously demonstrated that glutamatergic activity in the DLS is necessary for binge-like alcohol drinking in C57BL/6J mice, another high drinking mouse. Because of this, we hypothesised that DLS glutamatergic activity would gate binge-like alcohol drinking in cHAP mice. cHAP mice underwent bilateral cannulation into the DMS or DLS and were allowed free-access to 20% alcohol for 2 h each day for 11 days. Mice were microinjected with the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) antagonist, NBQX, into the DMS or DLS immediately prior to alcohol access. AMPAR protein expression was also assessed in a separate group of animals in the DMS and DLS following an 11-day drinking history. We found that intra-DMS (but not intra-DLS) NBQX alters binge alcohol drinking, with intra-DMS NBQX increasing alcohol consumption. We also found that the ratio of GluA1 to GluA2 differs across dorsal striatal subregions. Together, these findings suggest that glutamatergic activity in the DMS may serve to limit binge drinking in cHAP mice.

Salivary microbiota composition before and after use of proton pump inhibitors in patients with laryngopharyngeal reflux: a self-control study.

BACKGROUND: Issues associated with proton pump inhibitor (PPI) usage have been documented. PPIs affect the gastrointestinal microbiome, as well as the saliva microbiota of healthy individuals. However, the alterations in the saliva microbiota of laryngopharyngeal reflux (LPR) patients remain unclear. This study aims to examine the composition of saliva microbiota in LPR patients before and after PPI usage through a self-controlled study. METHODS: Thirty-two adult LPR patients participated in the study. Saliva samples were collected before and after an 8-week regimen of twice-daily administration of 20-mg esomeprazole. The impact of PPI administration on bacterial communities was assessed using 16 S rRNA gene sequencing. The functional and metabolic changes in saliva microbial communities after PPI usage were analyzed using PICRUSt2 based on our 16 S rRNA gene sequencing results. RESULTS: The alpha diversity within the salivary microbiota, as measured by the PD-whole-tree index, exhibited a significant difference between samples collected before and after PPI application (P = 0.038). Additionally, PCoA analysis of unweighted UniFrac distances (beta diversity) revealed distinct separation of saliva sample microbiota structures before and after PPI application in LPR patients, with statistical significance (Adonis test, R2 = 0.063, P< 0.010). Taxon-based analysis indicated that PPI administration increased the abundance of Epsilonproteobacteria, Campylobacterales, Campylobacteraceae, Campylobacter, and Campylobacter_gracilis, while reducing the abundance of Lactobacillaceae and Lactobacillus in salivary samples ( P< 0.050). Using LEfSe to compare bacterial abundances, Bacillaceae and Anoxybacillus were found to be enriched before PPI usage in LPR patients. Furthermore, the proportion of genes responsible for indole alkaloid biosynthesis in the salivary microbiota of LPR patients significantly increased after PPI therapy (P< 0.050). CONCLUSIONS: These findings indicate that PPIs induce alterations in the salivary microbiota of LPR patients. CHINESE CLINICAL TRIAL REGISTRY: No. ChiCTR2300067507. Registered on January 10,2023 retrospectively.

Analysis of low-density lipoprotein receptor gene mutations in a family with familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is a common monogenic autosomal dominant disorder, primarily mainly caused by pathogenic mutations in the low-density lipoprotein receptor (LDLR) gene. Through phenotypic-genetic linkage analysis, two LDLR pathogenic mutations were identified in FH families: c.G1027A (p.Gly343Ser) and c.G1879A (p.Ala627Thr). MATERIALS AND METHODS: Whole exome sequencing was conducted on the proband with familial hypercholesterolemia to identify the target gene and screen for potential pathogenic mutations. The suspicious responsible mutation sites in 14 family members were analyzed using Sanger sequencing to assess genotype-phenotype correlations. Mutant and wild type plasmids were constructed and transfected into HEK293T cells to evaluate LDLR mRNA and protein expression. In parallel, bioinformatics tools were employed to predict structural and functional changes in the mutant LDLR. RESULTS: Immunofluorescence analysis revealed no significant difference in the intracellular localization of the p.Gly343Ser mutation, whereas protein expression of the p.Ala627Thr mutation was decreased and predominantly localized in the cytoplasm. Western blotting has showed that protein expression levels of the mutant variants were markedly declined in both cell lysates and supernatants. Enzyme linked immunosorbent assay has demonstrated that LDLR protein levels in the supernatant of cell culture medium was not significant different from those of the wild-type group. However, LDLR protein levels in the cell lysate of both the Gly343Ser and Ala627Thr variants groups were significantly lower than those in the wild-type group. Bioinformatic predictions further suggested that these mutations may affect post-translational modifications of the protein, providing additional insight into the mechanisms underlying the observed reduction in protein expression. CONCLUSIONS: In this study, we identified two heterozygous pathogenic variants in the LDLR gene, c.G1027A (p.Gly343Ser) and c.G1879A (p.Ala627Thr), in a family with familial hypercholesterolemia. We also conducted preliminary investigations into the mechanisms by which these mutations contribute to disease pathology.

Recombinant Marek's disease virus type 1 provides full protection against H9N2 influenza A virus in chickens.

The H9N2 subtype of the avian influenza virus (AIV) poses a significant threat to the poultry industry and human health. Recombinant vaccines are the preferred method of controlling H9N2 AIV, and Marek's disease virus (MDV) is the ideal vector for recombinant vaccines. During this study, we constructed two recombinant MDV type 1 strains that carry the hemagglutinin (HA) gene of AIV to provide dual protection against both AIV and MDV. To assess the effects of different MDV insertion sites on the protective efficacy of H9N2 AIV, the HA gene of H9N2 AIV was inserted in UL41 and US2 of the MDV type 1 vector backbone to obtain recombinant viruses rMDV-UL41/HA and rMDV-US2/HA, respectively. An indirect immunofluorescence assay showed sustained expression of HA protein in both recombinant viruses. Additionally, the insertion of the HA gene in UL41 and US2 did not affect MDV replication in cell cultures. After immunization of specific pathogen-free chickens, although both the rMDV-UL41/HA and rMDV-US2/HA groups exhibited similar levels of hemagglutination inhibition antibody titers, only the rMDV-UL41/HA group provided complete protection against the H9N2 AIV challenge, and also offered complete protection against challenge with MDV. These results demonstrated that rMDV-UL41/HA could be used as a promising bivalent vaccine strain against both H9N2 avian influenza and Marek's disease in chickens.

Drug resistance and tumor immune microenvironment: An overview of current understandings (Review).

The use of antitumor drugs represents a reliable strategy for cancer therapy. Unfortunately, drug resistance has become increasingly common and contributes to tumor metastasis and local recurrence. The tumor immune microenvironment (TME) consists of immune cells, cytokines and immunomodulators, and collectively they influence the response to treatment. Epigenetic changes including DNA methylation and histone modification, as well as increased drug exportation have been reported to contribute to the development of drug resistance in cancers. In the past few years, the majority of studies on tumors have only focused on the development and progression of a tumor from a mechanistic standpoint; few studies have examined whether the changes in the TME can also affect tumor growth and drug resistance. Recently, emerging evidence have raised more concerns regarding the role of TME in the development of drug resistance. In the present review, it was discussed how the suppressive TME adapts to drug resistance characterized by the cooperation of immune cells, cytokines, immunomodulators, stromal cells and extracellular matrix. Furthermore, it was reviewed how these immunological or metabolic changes alter immuno­surveillance and thus facilitate tumor drug resistance. In addition, potential targets present in the TME for developing novel therapeutic strategies to improve individualized therapy for cancer treatment were revealed.

[Structural design of "fitness" and "feasibility" of body-fitted stent and its mechanical analysis].

To address the conflict between the "fitness" and "feasibility" of body-fitted stents, this paper investigates the impact of various smoothing design strategies on the mechanical behaviour and apposition performance of stent. Based on the three-dimensional projection method, the projection region was fitted with the least squares method (fitting orders 1-6 corresponded to models 1-6, respectively) to achieve the effect of smoothing the body-fitted stent. The simulation included the crimping and expansion process of six groups of stents in stenotic vessels with different degrees of plaque calcification. Various metrics were analyzed, including bending stiffness, stent ruggedness, area residual stenosis rate, contact area fraction, and contact volume fraction. The study findings showed that the bending stiffness, stent ruggedness, area residual stenosis rate, contact area fraction and contact volume fraction increased with the fitting order's increase. Model 1 had the smallest contact area fraction and contact volume fraction, 77.63% and 83.49% respectively, in the incompletely calcified plaque environment. In the completely calcified plaque environment, these values were 72.86% and 82.21%, respectively. Additionally, it had the worst "fitness". Models 5 and 6 had similar values for stent ruggedness, with 32.15% and 32.38%, respectively, which indicated the worst "feasibility" for fabrication and implantation. Models 2, 3, and 4 had similar area residual stenosis rates in both plaque environments. In conclusion, it is more reasonable to obtain the body-fitted stent by using 2nd to 4th order fitting with the least squares method to the projected region. Among them, the body-fitted stent obtained by the 2nd order fitting performs better in the completely calcified environment.

Construction of a redox-coupled pathway co-metabolizing glucose and acetate for high-yield production of butyl butyrate in Escherichia coli.

The carbon and energy efficiency of a biomanufacturing process is of crucial importance in determining its economic viability. Formate dehydrogenase has been demonstrated to be beneficial in regenerating NADH from formate produced during sugar metabolism, thereby creating energy-efficient systems. Nevertheless, introducing enzyme(s) for butyryl butyrate (BB) biosynthesis based on this system, only 1.64 g/L BB with 14.3 % carbon yield was obtained due to an imbalance in NADH-NAD+ turnover. To address the issue of NADH accumulation, a joint redox-balanced pathway for BB biosynthesis was developed in this study by coupling acetate and glucose metabolism. Following overexpression of acetyl-CoA synthetase in the BB-producing strain, acetate and glucose were co-utilized stoichiometrically and intracellular redox homeostasis was achieved. The engineered strain produced 29.02 g/L BB with carbon yield of 43.3 %, representing the highest yield ever reported for fermentative production of BB. It indicated the potential for developing a carbon- and energy-effective route for biomanufacturing.

A quantitative study of the effects of a dual layer coating drug-eluting stent on safety and efficacy.

A key strategy for increasing drug mass (DM) while maintaining good safety is to improve the drug release profile (RP). We designed a dual layer coating drug-eluting stent (DES) that exhibited smaller concentration gradients between the coating and the artery wall and significantly impacted the drug RP. However, a detailed understanding of the effects of the DES designed by our team on safety and efficacy is still lacking. The objective of this study was to provide a comprehensive multiscale computational framework that would allow us to probe the safety and efficacy of the DES we designed. This framework consisted of four coupled modules, namely (1) a mechanical stimuli module, simulating mechanical stimuli caused by percutaneous coronary intervention through a finite element analysis, (2) an inflammation module, simulating inflammation of vascular smooth muscle cells (VSMCs) induced by mechanical stimuli through an agent-based model (ABM), (3) a drug transport module, simulating drug transport through a continuum-based approach, and (4) a mitosis module, simulating VSMC mitosis through an ABM. Our results indicated that when the DM increased to two times the initial DM value, the DES we designed had higher safety and lower efficacy values than a conventional DES. When the DM increased to five times the initial DM value, the DES we designed had higher safety than a conventional DES, and negligible differences in efficacy compared with a conventional DES. In summary, the DES we designed exhibited a significant advantage in safety, but a slightly reduced efficacy compared with that of a conventional DES.

Prevalence, risk factors, psychological effects of children and adolescents with lower urinary tract symptoms: a large population-based study.

Background: Lower urinary tract symptoms (LUTS) are clinically frequent and seriously affect the psychological and mental health of children and adolescents. However, most studies on LUTS and its influence on the psychological behavior and mental health have focused on adults. This study aimed to investigate LUTS prevalence and associated factors in children and adolescents and explore its impact on psychological behavior. Materials and methods: From October 2019 to November 2021, an epidemiological LUTS survey was carried out on 6,077 children aged 6-15 years old in 12 primary and secondary schools in China by using anonymous questionnaires. Results: A total of 5,500 valid questionnaires were collected, and the total prevalence of four representative symptoms of LUTS: urgency, frequency, daytime urinary incontinence, and nocturnal enuresis was 19.46%, 14.55%, 9.75%, and 8.4%, respectively. The prevalence decreased with age, which decreased rapidly in children aged 6-12 years old. The incidence of LUTS in those who did not continue to use disposable diapers (DD) and began to perform elimination communication (EC) after the age of 1 was significantly higher than that of those who stopped using DD and started EC before 1 year of age (P < 0.05). There were significant differences in the occurrence of LUTS without toiled training (TT) (P < 0.05). The prevalence of LUTS in males was significantly higher than in females (P < 0.05). LUTS in children and adolescents with constipation was significantly higher compared to those without constipation (P < 0.05). The detection rate of abnormal psychological behavior in the LUTS group was 44.6%, which was significantly higher than that in the no LUTS group (21.4%, P < 0.05). The scores of emotional symptoms, conduct problems, hyperactivity, and peer communication problems were significantly higher in the LUTS group than the control group. Conclusions: In Mainland China, the prevalence of LUTS in children and adolescents is high. Continued use of DD after 1 year of age, history of urinary tract infection, lack of TT, and constipation were risk factors for LUTS. EC before 1 year of age is a protective factor for LUTS. The prevalence of psychological behavioral abnormalities is high in children and adolescents with LUTS, which needs to be more concerned.

Construction of Recombinant Marek's Disease Virus Co-Expressing VP1 and VP2 of Chicken Infectious Anemia Virus.

The chicken infectious anemia virus (CIAV) has been reported in major poultry-producing countries and poses a significant threat to the poultry industry worldwide. In this study, two Marek's disease virus (MDV) recombinants, rMDV-CIAV-1 and rMDV-CIAV-2, were generated by inserting the CIAV VP1 and VP2 genes into the MDV vaccine strain 814 at the US2 site using the fosmid-based rescue system. For rMDV-CIAV-1, an internal ribosome entry site was inserted between VP1 and VP2, so that both proteins were produced from a single open reading frame. In rMDV-CIAV-2, VP1 and VP2 were cloned into different open reading frames and inserted into the MDV genome. The recombinant viruses simultaneously expressed VP1 and VP2 in infected chicken embryo fibroblasts and exhibited growth kinetics similar to those of the parent MDV. The two recombinant viruses induced antibodies against CIAV in chickens. A single dose of the recombinant viruses provided strong protection against CIAV-induced anemia in chickens. These recombinant VP1- and VP2-expressing MDVs are potential vaccines against CIAV in chickens.

Effectiveness of the enterovirus A71 vaccine on hand, foot and mouth disease: a real-world study in China.

OBJECTIVES: For the prevention of hand, foot and mouth disease (HFMD), enterovirus A71 (EV-A71) vaccines have been utilized in China since 2016. To better inform vaccination strategies, we assess the real-world effectiveness of EV-A71 vaccination in China. METHODS: The analysis was based on surveillance data of HFMD caused by EV-A71 in children under the age of five in China, along with meteorological and demographic data. The seasonal autoregressive integrated moving average model and the interrupted time-series analysis were used to estimate the effectiveness of the EV-A71 vaccination on the EV-A71 HFMD incidence and to predict the counterfactual cases with no EV-A71 vaccine. RESULTS: Between 2010 and 2018, 6,712,613 cases of HFMD caused by EV-A71 were reported in children under five years old in 260 Chinese cities. During 2017-2018, the EV-A71 vaccination was associated with a reduction in EV-A71 HFMD incidence, with a relative risk of 0.83 (95% confidence interval (CI): 0.81-0.86), and an estimated reduction of 297,946 (95% CI: 250,534-346,658) cases. However, this association varied across cities (I2=85.6%, P<0.001) and the effectiveness of EV-A71 vaccination decreased as population density increased. Higher vaccination coverage was associated with greater effectiveness of the EV-A71 vaccination and an earlier point in EV-A71 cases reduction. Specifically, when the vaccination coverage exceeded approximately 20%, the relative risk was rapidly reduced to below 0.71 (95% CI: 0.69-0.72). CONCLUSIONS: Our study demonstrated that the EV-A71 vaccination was associated with a reduction in the incidence of EV-A71 HFMD, but the association varied with regions and was influenced by vaccination coverage and population density. To optimize EV-A71 HFMD prevention, increasing vaccination coverage (over 20%) is recommended for children under five years old.

Identification of Cables1 as a critical host factor that promotes ALV-J replication via genome-wide CRISPR/Cas9 gene knockout screening.

Avian leukosis virus subgroup J (ALV-J), a member of the genus Alpharetrovirus, possesses a small genome and exploits a vast array of host factors during its replication cycle. To identify host factors required for ALV-J replication and potentially guide the development of key therapeutic targets for ALV-J prevention, we employed a chicken genome-wide CRISPR/Cas9 knockout library to screen host factors involved in ALV-J infection within DF-1 cells. This screening revealed 42 host factors critical for ALV-J infection. Subsequent knockout assays showed that the absence of the genes encoding cycle-regulatory proteins, namely Cables1, CDK1, and DHFR, significantly inhibited ALV-J replication. Notably, Cables1 knockout cell lines displayed the most pronounced inhibitory effect. Conversely, overexpression assays confirmed that Cables1 significantly promotes ALV-J replication. Immunoprecipitation assays further indicated that Cables1 specifically interacts with the viral protein p15 (viral protease) among all ALV-J proteins, enhancing ALV-J p15 polyubiquitination. Additionally, we identified 26 lysine residues of ALV-J p15 as key sites for ubiquitination, and their replacement with arginine attenuated the replication ability of ALV-J in both in vitro and in vivo assays. This study demonstrates that Cables1 is a critical replication-dependent host factor of ALV-J by enhancing p15 ubiquitination and thereby promoting viral replication. Overall, these findings contribute to a deeper understanding of the ALJ-V replication mechanism and offer a potential target for the prevention and control of ALV-J infection.

Construction of recombinant Marek's disease virus co-expressing σB and σC of avian reoviruses.

Avian reoviruses (ARVs) cause viral arthritis or tenosynovitis, resulting in poor weight gain and increased feed conversion ratios in chickens. In this study, we generated three Marek's disease virus (MDV) recombinants, namely, rMDV-ARV-σB, rMDV-ARV-σC, and rMDV-ARV-σB + C, expressing ARV σB, σC, and both σB and σC, respectively. In rMDV-ARV-σB and rMDV-ARV-σC, the σB or σC gene was inserted into the US2 gene of MDV vaccine strain 814 using a fosmid-based rescue system. In rMDV-ARV-σB + C, the σB and σC genes were cloned into different expression cassettes, which were co-inserted into the US2 gene of the MDV 814 strain. In infected chicken embryo fibroblasts (CEFs), the recombinant virus rMDV-ARV-σB expressed σB, rMDV-ARV-σC expressed σC, and the rMDV-ARV-σB + C virus simultaneously expressed σB and σC. These recombinant viruses exhibited growth kinetics in CEFs similar to those of the parent MDV, and the inserted genes were stably maintained and expressed in the recombinant MDVs after 20 passages in cell cultures. These recombinant MDVs expressing σB and σC will provide potential vaccines against ARV infection in chickens.

Expression and diagnostic value of serum free light chain in lung cancer. / è¡€æ¸ æ¸¸ç¦»è½»é“¾åœ¨è‚ºç™Œä¸­çš„è¡¨è¾¾åŠè¯Šæ–­ä»·å€¼.

OBJECTIVES: The expression of serum free light chain (FLC) is abnormal in various diseases, but its role in lung cancer remains unclear. This study aims to investigate the expression and diagnostic value of serum FLC in lung cancer. METHODS: A total of 80 lung cancer patients treated at Xiangdong Hospital, Hunan Normal University from January to December 2021 were selected as the lung cancer group. Another 80 healthy individuals undergoing routine physical examinations during the same period were chosen as the control group. General information and serum κFLC and λFLC levels were collected for all subjects. Clinical indicators such as serum carcinoembryonic antigen (CEA), cytokeratin fragment antigen 21-1 (CYFRA21-1) levels, tumor diameter, histological type, TNM stage, and lymph node metastasis status were recorded for lung cancer patients. The expression levels of serum FLC [κFLC, λFLC, and FLC (κ+λ)] were compared between the lung cancer group and the control group. Lung cancer patients were grouped based on gender, age, smoking history, tumor diameter, TNM stage, histological type, and lymph node metastasis to compare differences in serum κFLC and λFLC levels. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic value of serum FLC alone and in combination with other indicators in lung cancer. RESULTS: The expression levels of serum FLC (κ+λ) and κFLC were significantly higher in the lung cancer group than those in the control group (both P<0.001), while there was no significant difference in serum λFLC levels between the 2 groups (P>0.05). There were no significant differences in serum κFLC levels among lung cancer patients with different tumor diameters, histological types, or TNM stages (all P>0.05); however, serum κFLC levels were higher in lung cancer patients with lymph node metastasis than in those without, with statistical significance (P=0.033). There were no significant differences in serum λFLC levels based on tumor diameter or histological type (both P>0.05), but serum λFLC levels were higher in stage III+IV and lymph node metastatic lung cancer patients compared to stage I+II and non-metastatic patients, with statistical significance (P=0.033 and P=0.019, respectively). The area under the curve (AUC) for κFLC and CEA in diagnosing lung cancer showed no significant difference (P=0.333). The combination of κFLC+CYFRA21-1 had the highest diagnostic efficacy (AUC=0.875) and sensitivity (71.3%). The AUC for the combined diagnosis of κFLC+λFLC+CEA+CYFRA21-1 was 0.915 (95% CI 0.860 to 0.953, P<0.001). CONCLUSIONS: Serum FLC is highly expressed in lung cancer and is associated with its invasion and metastasis. Serum FLC, particularly κFLC, has diagnostic value for lung cancer, and the combined detection of FLC, CEA, and CYFRA21-1 offers the best diagnostic efficacy.

[Causal relationship between obesity and male infertility: A two-sample Mendelian randomization study].

OBJECTIVE: To clarify the causal relationship between obesity and male infertility through Mendelian randomization (MR) study. METHODS: We assessed the causal effect of genetically predicted body mass index (BMI) on the risk of male infertility via a two-sample MR analysis, with the BMIs of 99 998 cases and 12 746 controls as the exposure factor and genetic information on male infertility obtained from a genome-wide association study of 73 479 Europeans. In the univariable MR (UVMR) analysis of the causal relationship, we mainly used inverse variance weighting (IVW), with MR-Egger regression and weighted median filtering as the supplementary methods. Sensitivity analyses including the Cochran's Q test, Egger intercept test, MR-PRESSO, leave-one-out analysis and funnel plot were performed to verify the robustness of the MR results. To evaluate the direct causal effects of BMI on MI risk, multivariable MR (MVMR) was performed. RESULTS: UVMR indicated a causal relationship between genetically predicted BMI and an increased risk of male infertility (OR: 1.237, 95% CI: 1.090－1.404, P = 0.001). Sensitivity analysis revealed little evidence of bias in the current study (P> 0.05). With such risk factors as type 2 diabetes, alcohol consumption and smoking adjusted, MVMR confirmed a direct causal effect of genetically predicted BMI on the risk of male infertility (P<0.05). CONCLUSION: Genetically predicted BMI may be associated with an increased risk of male infertility. Further studies are expected to explore the underlying mechanisms of this association and provide some new strategies for the prevention and treatment of BMI-related male infertility.

Imaging high-frequency voltage dynamics in multiple neuron classes of behaving mammals.

Fluorescent genetically encoded voltage indicators report transmembrane potentials of targeted cell-types. However, voltage-imaging instrumentation has lacked the sensitivity to track spontaneous or evoked high-frequency voltage oscillations in neural populations. Here we describe two complementary TEMPO voltage-sensing technologies that capture neural oscillations up to ~100 Hz. Fiber-optic TEMPO achieves ~10-fold greater sensitivity than prior photometry systems, allows hour-long recordings, and monitors two neuron-classes per fiber-optic probe in freely moving mice. With it, we uncovered cross-frequency-coupled theta- and gamma-range oscillations and characterized excitatory-inhibitory neural dynamics during hippocampal ripples and visual cortical processing. The TEMPO mesoscope images voltage activity in two cell-classes across a ~8-mm-wide field-of-view in head-fixed animals. In awake mice, it revealed sensory-evoked excitatory-inhibitory neural interactions and traveling gamma and 3-7 Hz waves in the visual cortex, and previously unreported propagation directions for hippocampal theta and beta waves. These technologies have widespread applications probing diverse oscillations and neuron-type interactions in healthy and diseased brains.

Adsorption mechanism and remediation of heavy metals from soil amended with hyperthermophilic composting products: Exploration of waste utilization.

Due to high humification, hyperthermophilic composting products (HP) show potential for remediating heavy metal pollution. However, the interaction between HP and heavy metals remains unclear. This study investigated the adsorption mechanism and soil remediation effect of HP on heavy metals. The results showed that the maximum adsorption capacity of HP increased by an average of 30.74 % compared to conventional composting products. HP transformed 34.87 % of copper, 42.55 % of zinc, and 35.63 % of lead from exchangeable and reducible forms into residual and oxidizable forms, thus reducing the soil risk level. In conclusion, HP significantly enhanced the adsorption of heavy metals and their transformation from unstable to stable forms, primarily due to the higher content of hydroxyl and carboxyl groups. This study aims to demonstrate the effectiveness of HP for remediating heavy metal pollution and to enhance the understanding of the underlying mechanism, which lays a foundation for waste utilization.

The Economic Burden of Brucellosis Care in China: Socioeconomic Status Inequality.

The economic burden of brucellosis care on patients can lead to significant financial strain, despite partial coverage by medical insurance. However, there is limited research on the out-of-pocket costs faced by brucellosis patients. Therefore, our study aimed to investigate the costs and out-of-pocket expenses of brucellosis care, specifically examining the varying socioeconomic status of patients in Xinjiang, China. We collected cost and demographic data from 563 respondents and their hospital bills and employed latent variable analysis to assess socioeconomic status. The majority of patients belonged to the middle and lower socioeconomic status categories (85.97%), and they were primarily farmers and herders (82.77%). The median direct cost per brucellosis episode was USD 688.65, with out-of-pocket expenses amounting to USD 391.44. These costs exceeded both the 2020 Xinjiang and national per capita health expenditures (USD 233.66 and USD 267.21, respectively). Notably, the overall medical reimbursement rate was 48.60%, and for outpatient costs, it was merely 12.82%. Despite higher out-of-pocket costs among high socioeconomic status patients, the percentage of income spent was higher (37.23%) for patients in the lower socioeconomic status group compared to other groups (16.25% and 12.96%). In conclusion, our findings highlight that brucellosis patients are predominantly from the middle and lower socioeconomic status, with high out-of-pocket expenses placing them under significant financial pressure. Moreover, there is notable inequity in economic consequences across different socioeconomic status groups. These results call for policy interventions aimed at reducing brucellosis-related poverty and promoting equitable access to care.

[Progress and perspectives of natural cell factories for chemical production from methanol].

Methanol has been considered one of the most important alternative carbon sources for the next-generation biomanufacturing due to its low price, mature production processes, and potential sustainability. Constructing microbial cell factories for methanol to chemical biotransformation has become a research hotspot in the green biomanufacturing industry. Focusing on the microorganisms that can naturally use methanol, we compare them with non-natural cell factories for chemical production from methanol. We discuss the key issues and challenges associated with natural cell factories for chemical production from methanol, summarize recent research progress surrounding these issues, and propose possible solutions to these challenges. This review helps to generate feasible guidelines and research strategies for the modification of natural cell factories for efficient methanol to chemical production in the future.