Drug-resistance characteristics, genetic diversity, and transmission dynamics of multidrug-resistant or rifampicin-resistant Mycobacterium tuberculosis from 2019 to 2021 in Sichuan, China.

BACKGROUND: Multidrug- or rifampicin-resistant tuberculosis (TB; MDR/RR-TB) is a significant public health threat. However, the mechanisms involved in its transmission in Sichuan, China are unclear. To provide a scientific basis for MDR/RR-TB control and prevention, we investigated the drug-resistance characteristics, genetic diversity, and transmission dynamics and analyzed the demographic and clinical characteristics of patients to identify risk factors for the acquisition of MDR/RR-TB in Sichuan, Western China. METHODS: Whole-genome sequencing was performed using a sample comprised of all MDR/RR-TB strains isolated from patients with pulmonary TB (≥ 15 years) at the 22 surveillance sites in Sichuan province between January 2019 and December 2021, to analyze genotypic drug resistance and genetic diversity. Moreover, we performed statistical analyses of the epidemiological characteristics and risk factors associated with the transmission dynamics of MDR/RR-TB. RESULTS: The final analysis included 278 MDR/RR TB strains. Lineage 2.2, the major sub-lineage, accounted for 82.01% (228/278) of isolates, followed by lineage 4.5 (9.72%, 27/278), lineage 4.4 (6.83%, 19/278), and lineage 4.2 (1.44%, 4/278). The drug resistance rates, ranging from high to low, were as follows: isoniazid (229 [82.37%]), streptomycin (177 [63.67%]), ethambutol (144 [51.80%]), pyrazinamide (PZA, 119 [42.81%]), fluoroquinolones (FQs, 93 [33.45%]). Further, the clofazimine, bedaquiline, and delamanid resistance rates were 2.88, 2.88, and 1.04%, respectively. The gene composition cluster rate was 32.37% (90/278). In addition, 83.81% (233/278) of MDR/RR-TB cases were determined to be likely caused by transmission. Finally, patients infected with lineage two strains and strains with the KatG S315T amino acid substitution presented a higher risk of MDR/RR-TB transmission. CONCLUSION: Transmission plays a significant role in the MDR/RR-TB burden in Sichuan province, and lineage 2 strains and strains harboring KatG S315T have a high probability of transmission. Further, high levels of FQ and PZA drug resistance suggest an urgent need for drug susceptibility testing prior to designing therapeutic regimens. New anti-TB drugs need to be used standardly and TB strains should be regularly monitored for resistance to these drugs.

The effect of anionic emulsifiers' diversity and manufacturing processes on the stability and mechanical properties of the water-based epoxy-emulsified asphalt.

Emulsified asphalt mixtures' cold mix and paving features facilitate asphalt pavements in fulfilling dual-carbon and energy-saving demands. Anionic emulsifiers can enhance emulsion stability, ensure uniform dispersion of oil and water, possess good decompression viscosity, thickening, and lubricating properties, and maintain good stability under acidic conditions. Nevertheless, anionic emulsified asphalt is restricted in engineering applications due to problems like its storage stability. In this paper, eight anionic emulsifiers and two preparation procedures were chosen for stability tests. Through static tests, storage tests, sieve residue tests, and laser particle size tests, the impacts of emulsifiers on the storage stability and dispersion of asphalt were analyzed. Waterborne epoxy resin exhibits excellent adhesive properties, mechanical properties, chemical resistance, and heat stability. A fluorescence microscope test, static and storage test, laser particle size test, and cementation test were employed to explore the effects of different preparation processes and waterborne epoxy mixing ratios on emulsified asphalt's storage stability, dispersion stability, and structural stability. The results showed that: (1) the emulsified asphalt prepared with the BWH-02 emulsifier exhibits the best storage stability, and blending with 20% of the waterborne epoxy modifier can notably enhance the bonding properties; (2) the shear strength of the BWH-02 waterborne epoxy emulsified asphalt prepared can reach 1.543 MPa, and the tensile viscosity can reach 0.848 MPa; (3), The emulsified asphalt prepared by the process of modification has better storage stability than that prepared by the side of the emulsification process. Moreover, the storage stability of emulsified asphalt prepared by emulsification and modification is superior to that of the emulsification and modification process. This research provides theoretical and technical support for popularizing and applying cold-mixed cold-paving asphalt mixtures.

Causal effects of sepsis on structural changes in cerebral cortex: A Mendelian randomization investigation.

Previous research has shown a strong correlation between sepsis and brain structure. However, whether this relationship represents a causality remains elusive. In this study, we employed Mendelian randomization (MR) to probe the associations of genetically predicted sepsis and sepsis-related death with structural changes in specific brain regions. Genome-wide association study (GWAS) data for sepsis phenotypes (sepsis and sepsis-related death) were obtained from the IEU OpenGWAS. Correspondingly, GWAS data for brain structural traits (volume of the subcortical structure, cortical thickness, and surface area) were derived from the ENIGMA consortium. Inverse variance weighted was mainly utilized to assess the causal effects, while weighted median and MR-Egger regression served as complementary methods. Sensitivity analyses were implemented with Cochran Q test, MR-Egger regression, and MR-PRESSO. In addition, a reverse MR analysis was carried out to assess the possibility of reverse causation. We identified that genetic liability to sepsis was normally significantly associated with a reduced surface area of the postcentral gyrus (ß = -35.5280, SE = 13.7465, P = .0096). The genetic liability to sepsis-related death showed a suggestive positive correlation with the surface area of fusiform gyrus (ß = 11.0920, SE = 3.6412, P = .0023) and posterior cingulate gyrus (ß = 3.6530, SE = 1.6684, P = .0286), While it presented a suggestive negative correlation with surface area of the caudal middle frontal gyrus (ß = -11.4586, SE = 5.1501, P = .0261) and frontal pole (ß = -1.0024, SE = 0.4329, P = .0206). We also indicated a possible bidirectional causal association between genetic liability to sepsis-related death and the thickness of the transverse temporal gyrus. Sensitivity analyses verified the robustness of the above associations. These findings suggested that genetically determined liability to sepsis might influence the specific brain structure in a causal way, offering new perspectives to investigate the mechanism of sepsis-related neuropsychiatric disorders.

Prognosis and Factors 4 to 10 Years After Deep Vein Thrombosis: A Long-Term Follow-up Cohort Study.

Post-thrombotic syndrome (PTS) is one of the most common long-term complications of lower extremity deep vein thrombosis (DVT). In order to study the long-term adverse prognosis of patients with DVT, explore the influencing factors for the prognosis of DVT, and provide a reliable reference for future research in the field of venous thrombosis, we collected and summarized information about the incidence of PTS, the PTS score and grading, the associated symptoms and drug-related adverse reactions in 501 patients with DVT. In our study, 54.1% of patients with DVT (271 of 501) experienced indications and manifestations of PTS, the male to female ratio was approximately 1:1. During the long-term follow up, the most common symptoms of PTS were anterior tibial edema and pain. By statistical analysis, we found that the outcome of thrombosis was the influencing factor of PTS score (1-4 points, P<.05). The grading of PTS was primarily influenced by the history of varicose veins and DVT in the lower extremities. The duration of taking antithrombotic drugs affected the outcome of thrombosis (P<.05), especially among the female patients. In addition, varied factors, such as lower extremity DVT complicated with pulmonary embolism and the duration of antithrombotic drug use were found to increase the chances of experiencing drug-related adverse reactions (odds ratio [OR]=2.798, 95% confidence interval [CI]: 1.413-5.541 / OR=2.778, 95% CI: 1.231-6.269). The above 2 factors were significant only among female patients with DVT (OR=4.03, 95% CI: 1.608-10.103 / OR=3.918, 95% CI: 1.123-13.669).

Vinyl-bearing sp2 carbon-conjugated covalent organic framework composites for enhanced electrochemical performance in hydrogen evolution reaction and lithium-sulfur batteries.

Vinyl-bearing triazine-functionalized covalent organic frameworks (COFs) have emerged as promising materials for electrocatalysis and energy storage. Guided by density functional theory calculations, a vinyl-enriched COF (VCOF-1) featuring a donor-acceptor structure was synthesized based on the Knoevenagel reaction. Moreover, the VCOF-1@Ru without pyrolysis was obtained through chemical coordination interactions between VCOF-1 and RuCl3, exhibiting enhanced electrocatalytic performance in the hydrogen evolution reaction when exposed to 0.5 M H2SO4. The results demonstrated that the protonation of VCOF-1@Ru enhanced the electrical conductivity and accelerated the generation of H2 on the catalytically active site Ru. Additionally, VCOF-1@CNT with a tubular structure was prepared by uniformly wrapping VCOF-1 onto carbon nanotubes (CNTs) and using it as a cathode for lithium-sulfur batteries by chemically and physically encapsulating S. The enhanced performance of VCOF-1@CNT was attributed to the effective suppression of lithium polysulfide migration. This suppression was achieved through several mechanisms, including the inverse vulcanization of vinyl on VCOF-1@CNT, the enhancement of material conductivity, and the interaction between N in the materials and Li ions. This study demonstrated a strategy for enhancing material performance by precisely modulating the COF structure at the molecular level.

Type III adenylyl cyclase is essential for follicular development in female mice and their reproductive lifespan.

Premature ovarian failure (POF) is a complex and heterogeneous disease that causes infertility and subfertility. However, the molecular mechanism of POF has not been fully elucidated. Here, we show that the loss of adenylyl cyclase III (Adcy3) in female mice leads to POF and a shortened reproductive lifespan. We found that Adcy3 is abundantly expressed in mouse oocytes. Adcy3 knockout mice exhibited the excessive activation of primordial follicles, progressive follicle loss, follicular atresia, and ultimately POF. Mechanistically, we found that mitochondrial oxidative stress in oocytes significantly increased with age in Adcy3-deficient mice and was accompanied by oocyte apoptosis and defective folliculogenesis. In contrast, compared with wild-type female mice, humanized ADCY3 knock-in female mice exhibited improved fertility with age. Collectively, these results reveal that the previously unrecognized Adcy3 signaling pathway is tightly linked to female ovarian aging, providing potential pharmaceutical targets for preventing and treating POF.

The causal relationship between rheumatoid arthritis and bronchiectasis: a bidirectional Mendelian randomization study.

Background: Several observational studies suggested an association between rheumatoid arthritis (RA) and bronchiectasis. Nevertheless, the presence of a causal relationship between these conditions is yet to be determined. This study aimed to investigate whether genetically predicted RA is associated with the risk of bronchiectasis and vice versa. Methods: We obtained RA genome-wide association study (GWAS) data from FinnGen consortium, and bronchiectasis GWAS data from IEU Open GWAS project. Univariate Mendelian randomization (MR) analysis was performed using inverse variance weighted (IVW) estimation as the main method. Furthermore, bidirectional and replication MR analysis, multivariate MR (MVMR), Mediation analysis, and sensitivity analyses were conducted to validate the findings. Results: In the UVMR analysis, the IVW results revealed that RA had an increased risk of bronchiectasis (OR = 1.18, 95% CI = 1.10-1.27; p = 2.34 × 10-6). In the reverse MR analysis, no evidence of a causal effect of bronchiectasis on the risk of RA was detected. Conversely, in the replication MR analysis, RA remained associated with an increased risk of bronchiectasis. Estimates remained consistent in MVMR analyses after adjusting for the prescription of non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids. Immunosuppressants were found to mediate 58% of the effect of the RA on bronchiectasis. Sensitivity analyses confirmed the stability of these associations. Conclusion: This study demonstrated a positive causal relationship between RA and an increased risk of bronchiectasis, offering insights for the early prevention of bronchiectasis in RA patients and shedding new light on the potential role of immunosuppressants as mediators in promoting the effects of RA on bronchiectasis.

Enhancing Structural Rigidity of Ultrahigh-Ni Oxide Through Al and Nb Dual-Bulk-Doping for High-Voltage Lithium-Ion Batteries.

The pursuit of high energy densities propels the design of next-generation nickel-based layered oxide cathodes. The utilization of low-cobalt, ultrahigh-nickel layered oxide cathodes, and the extension of operating voltages promise enhanced energy density. However, stability and safety face challenges associated with nickel content, including structural degradation, lattice oxygen evolution, and thermal instability. In this study, a promising strategy of Al and Nb dual-bulk-doping is presented in high-Ni cathode materials of LiNi0.96Co0.04O2 (NC) to stabilize the bulk structure, suppress oxygen release, and attain superior electrochemical performance at high voltages. The introduction of Al and Nb effectively raises the migration energy of Ni2+ into Li sites and stabilizes lattice oxygen through strengthened Al─O and Nb─O bonds. Furthermore, the substitution of high-valence Nb ions reduces the charge depletion of lattice oxygen and induces an ordered microstructure. The Al and Nb dual-bulk-doping strategy mitigates strain and stress associated with the H2↔H3 phase transition, reducing the generation and propagation of microcracks. The resulting Li(Ni0.96Co0.04)0.985Al0.01Nb0.005O2 (NCAN) cathode exhibits superior cycling stability, with a capacity retention of 77.8% after 300 cycles, even when operating at a high-voltage of 4.4 V, outperforming the NC (48.5%). This work provides a promising perspective for developing high-voltage and high-Ni cathode materials.

Evaluation of the ecological status of shallow-water coral reefs in China using a novel method and identification of environmental factors for coral decline.

Coral reefs worldwide have faced extensive damage due to natural catastrophes and anthropogenic disturbances.The decline can cause their widespread collapse and an inability to recover from natural disturbances, highlighting the urgent need for their protection. This study conducted an extensive ecological condition assessment of seven coral reef regions in China's offshore. Our findings revealed the presence of 204 species of scleractinian corals belonging to 16 families. Massive corals were the predominant reef-building corals in all regions. The degradation of coral reef ecosystems was apparent in the present compared to historical reef conditions. The ecosystem suffered varying degrees of damage in surveyed regions according to a novel assessment approach, impling more effective measures should be taken to mitigate the local pressures. Our research establishes a baseline for understanding the status of coral reefs that can be used in future and provides a crucial foundation to designate protective zones for their conservation.

LKB1 regulates autophagy through AMPK/TOR signaling pathway to alleviate the damage caused by Vibrio alginolyticus infection.

LKB1 (liver kinase B1) is a key upstream kinase of AMPK and plays an important role in various cellular activities. While the function and mechanism of LKB1 have been widely reported in the study of tumor, there are few reports on its role in bacterial infectious diseases, especially in shrimp. In the present study, molecular characterization revealed that LvLKB1 has an open reading frame (ORF) of 1266 bp encoding 421 amino acids with a molecular weight of about 48 KDa, including the kinase region, N-terminal regulatory domain and C-terminal regulatory domain. LvLKB1 in hepatopancreas and hemocytes was significantly upregulated after infection with Vibrio alginolyticus (V. alginolyticus). After silencing LvLKB1 gene in Litopenaeus vannamei (L. vannamei) and artificially infecting V. alginolyticus, the survival rate of L. vannamei was significantly decreased. Subsequently, it was found that the expression of inflammatory factors in hepatopancreas and hemocytes of shrimp was up-regulated, and the expression of lipid oxidation factors was decreased after silencing LKB1, leading to the phenomenon of lipid accumulation in hepatopancreas. In order to explore the mechanism, autophagy levels of shrimp were detected after silencing LKB1, which showed that autophagy levels in hepatopancreas and hemocytes were significantly reduced. Further studies conclusively showed that silencing LvLKB1 inhibited AMPK phosphorylation induced by V. alginolyticus infection, thereby activating TOR pathway and inhibiting autophagy in shrimp. These results indicate that LvLKB1 regulates autophagy through AMPK/TOR signaling pathway to alleviate the damage caused by V. alginolyticus infection.

Multi-functional carbon nanotube encapsulated by covalent organic frameworks for lithium-sulfur chemistry and photothermal electrocatalysis.

It is significant to tailor multifunctional electrode materials for storing sustainable energy in lithium-sulfur (Li-S) batteries and converting intermittent solar energy into H2, facilitated by electricity. In this context, COF-1@CNT obtained through interfacial interaction fulfilled both requisites via post-functionalization. Upon integrating COF-1@CNT with S as the cathode for Li-S batteries, the system exhibited an initial discharge capacity of 1360 mAh g-1. Subsequently, it maintained a sustained actual capacity even after undergoing 200 charge-discharge cycles at 0.5C. The performance improvement was attributed to the optimized conductivity due to the addition of carbon nanotubes (CNTs). Furthermore, the synergistic interaction between the nitrogen of COF-1 and lithium mitigated the shuttle effect in Li-S batteries. In the modified three-electrode electrolytic cell system, COF-1@CNT-Ru produced by COF-1@CNT with RuCl3 showed better electrochemical reactivity for photothermal-assisted hydrogen evolution reaction (HER). This effect was demonstrated by reducing the overpotential to 140 mV relative to the no-photothermal condition (180 mV) at a current density of 10 mA cm-2. This study marked the first simultaneous application of covalent organic frameworks (COFs) based materials in Li-S batteries and photothermal-assisted electrocatalysts. The modified electrocatalytic system held promise as a novel avenue for exploring solar thermal energy utilization.

Interspecific plant interaction structures the microbiomes of poplar-soil interface to alter nutrient cycling and utilization.

Terrestrial plants can influence the growth and health of adjacent plants through interspecific interaction. Here, the mechanisms of interspecific plant interaction on microbial function and nutrient utilization in the plant-soil interface (non-rhizosphere soil, rhizosphere soil, and root) were studied by soybean- and potato-poplar intercropping. First, metagenomics showed that soybean- and potato-poplar intercropping influenced the composition and co-occurrence networks of microbial communities in different ecological niches, with higher stability of the microbial community in soybean intercropping. Second, the gene abundance related to carbon metabolism, nitrogen cycling, phosphorus cycling, and sulfur cycling was increased at the poplar-soil interface in soybean intercropping. Moreover, soybean intercropping increased soil nutrient content and enzymatic activity. It showed higher metabolic potential in nutrient metabolism and transportation. Third, functional microorganisms that influenced nutrient cycling and transportation in different intercropping have been identified, namely Acidobacteria, Sphingomonas, Gemmatimonadaceae, Alphaproteobacteria, and Bradyrhizobium. Therefore, intercropping can construct microbial communities to alter metabolic functions and improve nutrient cycling and absorption. Interspecific plant interactions to influence the microbiome were revealed, opening up a new way for the precise regulation of plant microbiome.IMPORTANCEPoplar has the characteristics of wide distribution, strong adaptability, and fast growth, which is an ideal tree species for timber forest. In this study, metagenomics and elemental analysis were used to comprehensively reveal the effects of interspecific plant interactions on microbial communities and functions in different ecological niches. It can provide a theoretical basis for the development and application of the precise management model in poplar.

The miR-669a-5p/G3BP/HDAC6/AKAP12 Axis Regulates Primary Cilia Length.

Primary cilia are conserved organelles in most mammalian cells, acting as "antennae" to sense external signals. Maintaining a physiological cilium length is required for cilium function. MicroRNAs (miRNAs) are potent gene expression regulators, and aberrant miRNA expression is closely associated with ciliopathies. However, how miRNAs modulate cilium length remains elusive. Here, using the calcium-shock method and small RNA sequencing, a miRNA is identified, namely, miR-669a-5p, that is highly expressed in the cilia-enriched noncellular fraction. It is shown that miR-669a-5p promotes cilium elongation but not cilium formation in cultured cells. Mechanistically, it is demonstrated that miR-669a-5p represses ras-GTPase-activating protein SH3-domain-binding protein (G3BP) expression to inhibit histone deacetylase 6 (HDAC6) expression, which further upregulates A-kinase anchor protein 12 (AKAP12) expression. This effect ultimately blocks cilia disassembly and leads to greater cilium length, which can be restored to wild-type lengths by either upregulating HDAC6 or downregulating AKAP12. Collectively, these results elucidate a previously unidentified miR-669a-5p/G3BP/HDAC6/AKAP12 signaling pathway that regulates cilium length, providing potential pharmaceutical targets for treating ciliopathies.

What Do Higher Alanine Aminotransferase Levels Mean in Premature Ovarian Insufficiency?

The objective of this study was to investigate the relationship between alanine aminotransferase and related biochemical parameters and potential risk factors in women with premature ovarian insufficiency (POI). This is a retrospective cohort study with 126 POI patients (including subclinical POI, n= 27) and 130 healthy controls who visited our clinic between April 2021 to November 2022. Associations were investigated by multiple linear regression, Person correlation analysis, the Kruskal-Wallis test, Mann-Whitney U test, and the independent t-test. When compared to controls, analysis of POI patients showed that body mass index (BMI), uric acid (UA) and urea, alanine aminotransferase (ALT), aspartate aminotransferase (AST), monocyte/lymphocyte ratio, monocyte count (MONO), neutrophil count (NEUT), follicle-stimulating hormone (FSH), luteinizing hormone, and neutrophil/lymphocyte ratio (NLR) were significantly higher, while estradiol (E2), the lymphocyte count and the AST/ALT ratio were lower (P < 0.05). According to linear correlation, it was clear that BMI, FSH, white blood cell count (WBC), NEUT, MONO, UA, AST, and NLR were positively associated with ALT (r = 0.215, 0.388, 0.195, 0.187, 0.184, 0.605, 0.819, and 0.189, respectively, all P < 0.05) while E2 was negatively associated with ALT (r = -0.278, P < 0.05). In addition, multiple linear regression revealed a significant, independent, and positive correlation between AST, FSH, and ALT (B =1.403 and 0.069, respectively, P < 0.05). Analysis revealed that the levels of ALT were significantly higher in POI patients. In addition, BMI, FSH, UA, AST, MONO, NLR, NEUT, and WBC were positively associated with ALT in POI patients. E2 was negatively associated with ALT. Multiple linear regression revealed an independent and positive correlation between AST, FSH, and ALT. In addition, there was also a risk of liver function damage in women with POI and subclinical POI. If patients were diagnosed with POI, early examination and corresponding intervention will be required to effectively prevent the further development of liver disease.

Arabidopsis reticulons inhibit ROOT HAIR DEFECTIVE3 to form a stable tubular endoplasmic reticulum network.

The endoplasmic reticulum (ER) is a network of interconnected tubules and sheets stretching throughout the cytoplasm of plant cells. In Arabidopsis (Arabidopsis thaliana), ROOT HAIR DEFECTIVE3 (RHD3) mediates ER tubule fusion, while reticulon proteins induce ER membrane curvature to produce ER tubules. However, it is unclear if and how RHD3-reticulon interplay during the formation of the interconnected tubular ER network. We discovered that RHD3 physically interacts with Arabidopsis reticulon proteins, including reticulon-like protein subfamily B3 (RTNLB3), on ER tubules and at 3-way junctions of the ER. The RTNLB3 protein is widely expressed in Arabidopsis seedlings and localizes to ER tubules. Although the growth of knockout rtnlb3 mutant plants was relatively normal, root hairs of rtnlb3 were shorter than those of wild type. The ER in mature mutant cells was also more sheeted than that in wild type. rhd3 is known to have short roots and root hairs and less branched ER tubules in cells. Interestingly, rtnlb3 genetically antagonizes rhd3 in plant root development and in ER interconnectivity. We show that reticulons including RTNLB3 inhibit the ER fusion activity of RHD3, partly by interfering with RHD3 dimerization. We conclude that reticulon proteins negatively regulate RHD3 to balance its ER fusion activity for the formation of a stable tubular ER network in plant cell growth.

Targeted ablation of the left middle cervical ganglion prevents ventricular arrhythmias and cardiac injury induced by AMI.

Cardiac sympathetic overactivation is a critical driver in the progression of acute myocardial infarction (AMI). The left middle cervical ganglion (LMCG) is an important extracardiac sympathetic ganglion. However, the regulatory effects of LMCG on AMI have not yet been fully documented. In the present study, we detected that the LMCG was innervated by abundant sympathetic components and exerted an excitatory effect on the cardiac sympathetic nervous system in response to stimulation. In canine models of AMI, targeted ablation of LMCG reduced the sympathetic indexes of heart rate variability and serum norepinephrine, resulting in suppressed cardiac sympathetic activity. Moreover, LMCG ablation could improve ventricular electrophysiological stability, evidenced by the prolonged ventricular effective refractory period, elevated action potential duration, increased ventricular fibrillation threshold, and enhanced connexin43 expression, consequently showing antiarrhythmic effects. Additionally, compared with the control group, myocardial infarction size, circulating cardiac troponin I, and myocardial apoptosis were significantly reduced, accompanied by preserved cardiac function in canines subjected to LMCG ablation. Finally, we performed the left stellate ganglion (LSG) ablation and compared its effects with LMCG destruction. The results indicated that LMCG ablation prevented ventricular electrophysiological instability, cardiac sympathetic activation, and AMI-induced ventricular arrhythmias with similar efficiency as LSG denervation. In conclusion, this study demonstrated that LMCG ablation suppressed cardiac sympathetic activity, stabilized ventricular electrophysiological properties and mitigated cardiomyocyte death, resultantly preventing ischemia-induced ventricular arrhythmias, myocardial injury, and cardiac dysfunction. Neuromodulation therapy targeting LMCG represented a promising strategy for the treatment of AMI.

miR-2765 involved in ammonia nitrogen stress via negative regulation of autophagy in shrimp.

MicroRNA (miRNA) is a highly conserved non-coding tiny endogenous RNA molecule that regulates various cellular functions by inhibiting mRNA translation or promoting the degradation of proteins. In this study, we identified a specific miRNA (designed as Pva-miR-2765) from Penaeus vannamei, which widely distributed in different tissues of shrimp, with the highest concentration found in the intestine. Through fluorescence in situ hybridization (FISH), we observed that Pva-miR-2765 is primarily located in the cytoplasm. Interestingly, we found that the expression of Pva-miR-2765 significantly decreased in hemocytes, hepatopancreas and gill under ammonia nitrogen stress. Furthermore, when Pva-miR-2765 was silenced, the autophagy level in shrimp significantly increased. Additionally, Pva-miR-2765 was found to promote pathological damage in the hepatopancreas of shrimp. Subsequently, correlation analysis revealed a negative relationship between the expression of Pva-miR-2765 and PvTBC1D7. To confirm this interaction, we conducted a dual luciferase reporter gene assay, which demonstrated that Pva-miR-2765 inhibit the expression of PvTBC1D7 by interacting with its 3'UTR. And the expression level of PvTBC1D7 in shrimp decreased significantly under ammonia nitrogen stress in Pva-miR-2765 overexpressed. Our findings suggest that Pva-miR-2765 can reduce autophagy in P. vannamei by inhibiting the regulation of PvTBC1D7, thereby participating in the oxidative stress of shrimp caused by ammonia nitrogen stress.

An Arabidopsis Rab18 GTPase promotes autophagy by tethering ATG18a to the ER in response to nutrient starvation.

The expansion of autophagosomes requires a controlled association with the endoplasmic reticulum (ER). However, the mechanisms governing this process are not well defined. In plants, ATG18a plays a key role in autophagosome formation in response to stress, yet the factors regulating the process are unknown. This study finds that ATG18a acts as a downstream effector of RABC1, a member of the poorly characterized Rab18/RabC GTPase subclass in plants. Active RABC1 interacts with ATG18a on the ER, particularly under nutrient starvation. In rabc1 mutants, autophagy is compromised, especially under nutrient deprivation, affecting the ER association and expansion of ATG18a-positive autophagosomes. Furthermore, both dominant-negative and constitutively active RABC1 forms inhibit autophagy. The dominant inactive RABC1 impedes the ER association of ATG18a, whereas the constitutively active RABC1 delays ATG18a detachment from the ER. Collectively, RABC1 regulates the ER association and the subsequent detachment of ATG18a-positive autophagosomes during nutrient starvation.

Metabolic heterogeneity in different subtypes of malformations of cortical development causing epilepsy: a proton magnetic resonance spectroscopy study.

Background: The most common subtypes of malformations of cortical development (MCDs) are gray matter heterotopia (GMH), focal cortical dysplasia (FCD), and polymicrogyria (PMG). This study aimed to characterize the possible neurometabolic abnormalities and heterogeneity in different MCDs subtypes using proton magnetic resonance spectroscopy (1H-MRS). Methods: In this prospective cross-sectional study, we recruited 29 patients with MCDs and epilepsy, including ten with GMH, ten with FCD, and nine with PMG, as well as 25 age- and sex-matched healthy controls (HC) from the Epilepsy Center of West China Hospital of Sichuan University between August 2018 and November 2021. Inclusion criteria for the patients were based upon typical magnetic resonance imaging (MRI) findings of MCDs and full clinical assessment for epilepsy. Single-voxel point-resolved spectroscopy was used to acquire data from both the lesion and the normal-appearing contralateral side (NACS) in patients and from the frontal lobe in HC. Metabolite measures, including N-acetyl aspartate (NAA), myoinositol (Ins), choline (Cho), creatine (Cr), and glutamate + glutamine (Glx) concentrations, were quantitatively estimated with linear combination model (LCModel) software and corrected for the partial volume effect of cerebrospinal fluid (CSF). Results: The NAA concentration was lower and the Ins concentration was higher in the MCDs lesions than in the NACS and in HC (P=0.002-0.007), and the Cho and Cr concentrations were higher in MCDs lesions than in HC (P=0.001-0.016). Moreover, the Cho concentration was higher in NACS than in HC (P=0.015). In the GMH lesions, the only metabolic alteration was an NAA reduction (GMH_lesion vs. HC: P=0.001). In the FCD lesions, there were more metabolite abnormalities than in the other two subtypes, particularly a lower NAA and a higher Ins than in HC and NACS (P=0.012-0.042). In the PMG lesions, Cr (lesion vs. HC or NACS: P=0.017-0.021) and Glx (lesion vs. NACS: P=0.043) were increased, while NAA was normal. Correlation analysis revealed that the Cr concentration in MCDs lesions was positively correlated with seizure frequency (r=0.411; P=0.027). Conclusions: Based upon 1H-MRS, our study demonstrated that different MCDs subtypes exhibited variable metabolic features, which may be associated with distinct functional and cytoarchitectural properties.

Study on the correlation between bioelectrical impedance analysis index and protein energy consumption in maintenance dialysis patients.

BACKGROUND: Protein-energy wasting (PEW) has been reported to be pretty common in maintenance dialysis patients. However, the existing PEW diagnostic standard is limited in clinical use due to the complexity of it. Bioelectrical impedance analysis (BIA), as a non-invasive nutritional assessment method, can objectively and quantitatively analyze the changes of body tissue components under different nutritional states. We aim to explore the association between PEW and BIA and establish a reliable diagnostic model of PEW. METHODS: We collected cross-sectional data of 609 maintenance dialysis patients at the First Affiliated Hospital, College of Medicine, Zhejiang University. PEW was diagnosed according to International Society of Renal Nutrition and Metabolism (ISRNM) criteria. Among them, 448 consecutive patients were included in the training set for the establishment of a diagnostic nomogram. 161 consecutive patients were included for internal validation. 52 patients from Zhejiang Hospital were included for external validation of the diagnostic model. Correlation analysis of BIA indexes with other nutritional indicators was performed. Logistic regression was used to examine the association of BIA indexes with PEW. 12 diagnostic models of PEW in maintenance dialysis patients were developed and the performance of them in terms of discrimination and calibration was evaluated using C statistics and Hosmer-Lemeshow-type χ2 statistics. After comparing to existing diagnostic models, and performing both internal and external validation, we finally established a simple but reliable PEW diagnostic model which may have great value of clinical application. RESULTS: A total of 609 individuals from First Affiliated Hospital, College of Medicine, Zhejiang University and 52 individuals from Zhejiang Hospital were included. After full adjustment, age, peritoneal dialysis (compared to hemodialysis), subjective global assessment (SGA, compared to non-SGA) and water ratio were independent risk factors, while triglyceride, urea nitrogen, calcium, ferritin, BCM, VFA and phase angle were independent protective factors of PEW. The model incorporated water ratio, VFA, BCM, phase angle and cholesterol revealed best performance. A nomogram was developed according to the results of model performance. The model achieved high C-indexes of 0.843 in the training set, 0.841 and 0.829 in the internal and external validation sets, respectively, and had a well-fitted calibration curve. The net reclassification improvement (NRI) showed 8%, 13%, 2%, 38%, 36% improvement of diagnostic accuracy of our model compared with "PEW score model", "modified PEW score model", "3-index model", "SGA model" and "BIA decision tree model", respectively. CONCLUSIONS: BIA can be used as an auxiliary tool to evaluate PEW risk and may have certain clinical application value.