Metabolic Engineering of Corynebacterium glutamicum for the High-Level Production of l-Valine under Aerobic Conditions.

l-Valine, an essential amino acid, serves as a valuable compound in various industries. However, engineering strains with both high yield and purity are yet to be delivered for microbial l-valine production. We engineered a Corynebacterium glutamicum strain capable of highly efficient production of l-valine. We initially introduced an acetohydroxy acid synthase mutant from an industrial l-valine producer and optimized a cofactor-balanced pathway, followed by the activation of the nonphosphoenolpyruvate-dependent carbohydrate phosphotransferase system and the introduction of an exogenous Entner-Doudoroff pathway. Subsequently, we weakened anaplerotic pathways, and attenuated the tricarboxylic acid cycle via start codon substitution in icd, encoding isocitrate dehydrogenase. Finally, to balance bacterial growth and l-valine production, an l-valine biosensor-dependent genetic circuit was established to dynamically repress citrate synthase expression. The engineered strain Val19 produced 103 g/L of l-valine with a high yield of 0.35 g/g glucose and a productivity of 2.67 g/L/h. This represents the highest reported l-valine production in C. glutamicum via direct fermentation and exhibits potential for its industrial-scale production, leveraging the advantages of C. glutamicum over other microbes.

Reverse Hydrogen Spillover on Metal Oxides for Water-Promoted Catalytic Oxidation Reactions.

Understanding the water-involved mechanism on metal oxide surface and the dynamic interaction of water with active sites is crucial in solving water poisoning in catalytic reactions. Herein, this work solves this problem by designing the water-promoted function of metal oxides in the ethanol oxidation reaction. In situ multimodal spectroscopies unveil that the competitive adsorption of water-dissociated *OH species with O2 at Sn active sites results in water poisoning and the sluggish proton transfer in CoO-SnO2 imparts water-resistant effect. Carbon material as electron donor and proton transport channel optimizes the Co active sites and expedites the reverse hydrogen spillover from CoO to SnO2. The water-promoted function arises from spillover protons facilitating O2 activation on the SnO2 surface, leading to crucial *OOH intermediate formation for catalyzing C-H and C-C cleavage. Consequently, the tailored CoO-C-SnO2 showcases a remarkable 60-fold enhancement in ethanol oxidation reaction compared to bare SnO2 under high-humidity conditions.

Epidermal growth factor-loaded, dehydrated physical microgel-formed adhesive hydrogel enables integrated care of wet wounds.

Integrated wound care, a sequential process of promoting wound hemostasis, sealing, and healing, is of great clinical significance. However, the wet environment of wounds poses formidable challenges for integrated care. Herein, we developed an epidermal growth factor (EGF)-loaded, dehydrated physical microgel (DPM)-formed adhesive hydrogel for the integrated care of wet wounds. The DPMs were designed using the rational combination of hygroscopicity and reversible crosslinking of physical hydrogels. Unlike regular bioadhesives, which consider interfacial water as a barrier to adhesion, DPMs utilize water to form desirable adhesive structures. The hygroscopicity allowed the DPMs to absorb interfacial water and subsequently, the interfacial adhesion was realized by the interactions between tissue and DPMs. The reversible crosslinks further enabled DPMs to integrate into hydrogels (DPM-Gels), thus achieving wet adhesion. Importantly, the water-absorbing gelation mode of DPMs enabled facile loading of biologically active EGF to promote wound healing. We demonstrated that the DPM-Gels possessed wet tissue adhesive performance, with about 40 times the wet adhesive strength of fibrin glue and about 4 times the burst pressure of human blood pressure. Upon application at the injury site, the EGF-loaded DPM-Gels sequentially promoted efficient wound hemostasis, stable sealing, and quick healing, achieving integrated care of wet wounds.

Changes on Cognition and Brain Network Temporal Variability After Pediatric Neurosurgery.

BACKGROUND AND OBJECTIVES: Pediatric intracranial space-occupying lesions are common, with prognoses improving markedly in recent years, significantly extending survival. As such, there is an imperative to pay increased attention to the postoperative cognitive functions and brain network alterations in these children because these factors significantly influence their quality of life. Temporal variability (TV) analysis of brain networks captures the full extent of resting-state activities, reflecting cognitive functions and rehabilitation potential. However, previous research rarely uses TV analyses and most focus on adults or children after multidisciplinary treatments, not reflecting the combined effect caused by neurosurgery only and self-repair. This study gives our insights into this field from a holistic perspective. METHODS: We studied 35 children with intracranial space-occupying lesions, analyzing pre- and postsurgery MRI and cognitive tests. We used TV analysis to assess changes and correlated imaging indicators with cognitive performance. RESULTS: We observed a tendency for cognitive recovery after about 3 months postsurgery, primarily in the domains of social cognition and nonverbal reasoning. TV analysis of brain networks indicated increased nodal variability within systems such as the visual and sensorimotor networks, which are integral to external interactions. Correlative analysis showed that alterations in certain occipital regions were associated with changes in social cognition and nonverbal reasoning. CONCLUSION: These findings suggest significant intrinsic repair in cognitive functions and brain networks at around 3 months postneurosurgery in children. This study not only enriches our comprehension of postoperative cognitive and brain network self-repair processes in children but also furnishes potential therapeutic targets for rehabilitation interventions and establishes a theoretical foundation for proactive surgical interventions.

Long-term Application of Agricultural Amendments Regulate Hydroxyl Radicals Production during Oxygenation of Paddy Soils.

Hydroxyl radicals (•OH) play a significant role in contaminant transformation and element cycling during redox fluctuations in paddy soil. However, these important processes might be affected by widely used agricultural amendments, such as urea, pig manure, and biochar, which have rarely been explored, especially regarding their impact on soil aggregates and associated biogeochemical processes. Herein, based on five years of fertilization experiments in the field, we found that agricultural amendments, especially coapplication of fertilizers and biochar, significantly increased soil organic carbon contents and the abundances of iron (Fe)-reducing bacteria. They also substantially altered the fraction of soil aggregates, which consequently enhanced the electron-donating capacity and the formation of active Fe(II) species (i.e., 0.5 M HCl-Fe(II)) in soil aggregates (0-2 mm), especially in small aggregates (0-3 µm). The highest contents of active Fe(II) species in small aggregates were mainly responsible for the highest •OH production (increased by 1.7-2.4-fold) and naphthalene attenuation in paddy soil with coapplication of fertilizers and biochar. Overall, this study offers new insights into the effects of agricultural amendments on regulating •OH formation in paddy soil and proposes feasible strategies for soil remediation in agricultural fields, especially in soils with frequent occurrences of redox fluctuations.

Soil moisture alters the responses of alpine ecosystem productivity to environmental factors, especially VPD, on the Qinghai-Tibetan Plateau.

Water availability, which can be represented by soil water content (SWC), plays a crucial role in plant growth and productivity across the cold and arid Qinghai-Tibetan Plateau. However, the indirect effects of SWC are less well understood, and a more comprehensive understanding of its regulating effects may enhance the recognition of its importance, as this factor is pivotal for accurately predicting the future response of alpine ecosystems to climate change. In this study, in situ eddy covariance observation data from typical alpine ecosystems and satellite data covering the Qinghai-Tibetan region were used to comprehensively reveal the effects of SWC on ecosystem productivity. The results indicated that SWC played an important role in regulating the responses of gross primary productivity (GPP) to other environmental factors over both time and space, especially in terms of the responses of GPP to vapor pressure deficit (VPD). The regulating effect can be summarized as follows: there was a specific SWC value (SWC = 0.24 m3 m-3 on the Qinghai-Tibetan Plateau) above which SWC was no longer the primary limiting factor. The responses of GPP to certain environmental factors shifted from negative to positive when the SWC increased above this value. The responses of GPP to VPD exhibited the highest sensitivity to the regulating effects of SWC, with a general response pattern found across different temporal and spatial scales. The findings revealed divergent responses of GPP to environmental factors under different SWC conditions and between arid and humid regions, emphasizing the importance of soil water conditions. These findings suggest that water conditions should be given primary consideration in global change studies.

The value of D-dimer and platelet-lymphocyte ratio combined with CT signs for predicting intestinal ischemia in patients with bowel obstruction.

OBJECTIVE: To investigate the diagnostic value of D-dimer, platelet-lymphocyte rate (PLR) and CT signs for intestinal ischemia in patients with bowel obstruction. METHODS: We retrospectively analyzed the clinical and imaging data of 105 patients diagnosed with bowel obstruction, and performed univariate and multivariate analyses to determine the independent risk factors for intestinal ischemia in patients with bowel obstruction. Moreover, the receiver operating characteristic curve (ROC) was plotted to examine the diagnostic value of D-dimer, PLR and CT signs in patients with bowel obstruction. Besides, Kappa tests were used to assess inter-observer agreement. RESULTS: We included 56 men (53%) and 49 women (47%) with mean age of 66.05 ± 16 years. Univariate and multivariate analyses showed that D-dimer, PLR and two significant CT signs (i.e., increased unenhanced bowel-wall attenuation and mesenteric haziness) were independent risk factors for intestinal ischemia in patients with bowel obstruction. ROC analysis showed that the combined use of D-dimer, PLR and the said two CT signs had better performance than single indicators in predicting intestinal ischemia in patients with bowel obstruction. The area under the curve (AUC) of the joint model III was 0.925 [95%CI: 0.876-0.975], with a sensitivity of 79.2% [95CI%: 67.2-91.1] and a specificity of 91.2% [95%CI: 83.7-98.9]. CONCLUSION: The combined use of D-dimer, PLR and CT signs has high diagnostic value for intestinal ischemia in patients with bowel obstruction and will prompt surgical exploration to evaluate intestinal blood flow.

PyBox-La(OTf)3-Catalyzed Enantioselective Diels-Alder Cycloadditions of 2-Alkenoylpyridines with Cyclopentadiene.

The PyBox-La(OTf)3-catalyzed enantioselective Diels-Alder cycloaddition of 2-alk-2-enoylpyridines with cyclopentadiene is realized, producing enantiopure disubstituted norbornenes, which possess four contiguous stereocenters and are biologically relevant structures in up to 92:8 dr and 99:1 er.

Destination Restaurants' Practices and the Production of Locality: The Case of Michelin Restaurants in China.

Dining plays a pivotal role in the travel experience, with numerous studies identifying the significant impacts of restaurant attributes on tourists' destination experiences and their sense of place. The identified attributes include the origin of food produce, menu design, the physical and social servicescape, and restaurant reputation, all of which have the potential to enhance customers' sense of place. Therefore, based on theories of the production of locality, this study explores how destination restaurants "put place on the plate" and identifies how destination restaurants promote place. Semi-structured interviews were conducted with the representatives of seventeen Michelin (one star, two stars, three stars, and Bib Gourmand)-awarded restaurants across Mainland China. The results reveal three primary strategies employed by destination restaurants in promoting place: forging partnerships with the local community to produce, present, and reproduce localities; leveraging local knowledge embedded in the local produce, recipes, cooking techniques, and local culture; and practicing translocality to introduce a regional cuisine to diverse and cosmopolitan consumers. This research provides a comprehensive understanding of the way in which notions of locality and place are used by destination restaurants and the way in which this may promote not only restaurants but also regional culinary cultures and destination attractiveness.

Dual-Component Interlayer Enables Uniform Lithium Deposition and Dendrite Suppression for Solid-State Batteries.

ß-Lithium thiophosphate (LPS) exhibits high Li+ conductivity and has been identified as a promising ceramic electrolyte for safe and high-energy-density all-solid-state batteries. Integrating LPS into solid-state lithium (Li) batteries would enable the use of a Li electrode with the highest deliverable capacity. However, LPS-based batteries operate at a limited current density before short-circuiting, posing a major challenge for the development of application-relevant batteries. In this work, we designed a dual-component interfacial protective layer called LiSn-LiN that forms in situ between the Li electrode and LPS electrolyte. The LiSn component, Li22Sn5, exhibits enhanced Li diffusivity compared with the metallic lithium and facilitates a more uniform lithium deposition across the electrode surface, thus eliminating Li dendrite formation. Meanwhile, the LiN component, Li3N, shows enhanced mechanical stiffness compared with LPS and functions to suppress dendrite penetration. This chemically robust LiSn-LiN interlayer provides a more than doubled deliverable critical current density compared to systems without interfacial protection. Through combined XPS and XAFS analyses, we determined the local structure and the formation kinetics of the key functional Li22Sn5 phase formed via the electrochemical reduction of a Sn3N4 precursor. This work demonstrates an example of the structural-specific design of a protective interlayer with a desired function - dendrite suppression. The structure of a functional protective layer for a given solid-state battery should be tailored based on the given battery configuration and its unique interfacial chemistry.

Enhanced abscopal anti-tumor response via a triple combination of thermal ablation, IL-21, and PD-1 inhibition therapy.

Despite the success of immune checkpoint inhibitors (ICIs) in treating solid tumors, lots of patients remain unresponsive to this therapy. Microwave ablation (MWA) stimulates systemic adaptive immunity against tumor cells by releasing tumor antigens. Additionally, IL-21 has demonstrated importance in stimulating T-cell effector function. The combination of these three therapies-MWA, IL-21, and anti-PD-1 monoclonal antibodies (mAbs)-has yet to be explored in the context of cancer treatment.In this study, we explored the impact of thermal ablation on IL-21R expression in tumor-infiltrating lymphocytes (TILs). Subsequently, we assessed alterations in the tumor microenvironment (TME) and peripheral lymphoid organs. Additionally, we conducted a thorough examination of tumor-infiltrating CD45+ immune cells across various treatment groups using single-cell RNA sequencing (scRNA-seq). Moreover, we determined the potential anti-tumor effects of the triple combination involving MWA, IL-21, and anti-PD-1 mAbs.Our findings revealed that MWA upregulated the expression of IL-21R on various immune cells in the untreated tumors. The combination of MWA with IL-21 exhibited a robust abscopal anti-tumor effect, enhancing the effector function of CD8+ T cells and facilitating dendritic cells' maturation and antigen presentation in the untreated tumor. Notably, the observed abscopal anti-tumor effect resulting from the combination is contingent upon T-cell recirculation, indicating the reliance of systemic adaptive immunity for this treatment regimen. Additionally, the combination of MWA, IL-21, and PD-1 mAbs demonstrated profound abscopal anti-tumor efficacy. Our findings provide support for further clinical investigation into a triple combination therapy involving MWA, IL-21, and ICIs for the treatment of metastatic cancer.

Tissue-adhesive, stretchable and compressible physical double-crosslinked microgel-integrated hydrogels for dynamic wound care.

Integrated wound care through sequentially promoting hemostasis, sealing, and healing holds great promise in clinical practice. However, it remains challenging for regular bioadhesives to achieve integrated care of dynamic wounds due to the difficulties in adapting to dynamic mechanical and wet wound environments. Herein, we reported a type of dehydrated, physical double crosslinked microgels (DPDMs) which were capable of in situ forming highly stretchable, compressible and tissue-adhesive hydrogels for integrated care of dynamic wounds. The DPDMs were designed by the rational integration of the reversible crosslinks and double crosslinks into micronized gels. The reversible physical crosslinks enabled the DPDMs to integrate together, and the double crosslinked characteristics further strengthen the formed macroscopical networks (DPDM-Gels). We demonstrated that the DPDM-Gels simultaneously possess outstanding tensile (∼940 kJ/m3) and compressive (∼270 kJ/m3) toughness, commercial bioadhesives-comparable tissue-adhesive strength, together with stable performance under hundreds of deformations. In vivo results further revealed that the DPDM-Gels could effectively stop bleeding in various bleeding models, even in an actual dynamic environment, and enable the integrated care of dynamic skin wounds. On the basis of the remarkable mechanical and appropriate adhesive properties, together with impressive integrated care capacities, the DPDM-Gels may provide a new approach for the smart care of dynamic wounds. STATEMENT OF SIGNIFICANCE: Integrated care of dynamic wounds holds great significance in clinical practice. However, the dynamic and wet wound environments pose great challenges for existing hydrogels to achieve it. This work developed robust adhesive hydrogels for integrated care of dynamic wounds by designing dehydrated, physical double crosslinked microgels (DPDMs). The reversible and double crosslinks enabled DPDMs to integrate into macroscopic hydrogels with high mechanical properties, appropriate adhesive strength and stable performance under hundreds of external deformations. Upon application at the injury site, DPDM-Gels efficiently stopped bleeding, even in an actual dynamic environment and showed effectiveness in integrated care of dynamic wounds. With the fascinating properties, DPDMs may become an effective tool for smart wound care.

Therapeutic effect of Periploca forrestii on collagen-induced arthritis in rats through JAK2/Nf-κB pathway.

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects the body. Periploca forrestii was a miao ethnic drug in China that was used to treat arthritis for hundreds of years. But, the therapeutic mechanism is so far unknown. Therefore, the chemical component and effect of Periploca forrestii on arthritis in rats were studied using HPLC-QTOF MS, micro-CT, and other experiments in this paper. Method: Male Sprague-Dawley rats were used to assess the in vivo activity. HPLC QTOF-MS was used to analyze the chemical profile of the P. forrestii (PF). Bovine type II collagen and Complete Freund's Adjuvant were used to stimulate and construct the collagen-induced arthritis (CIA) model. Three dosages of PF (100 mg/kg, 200 mg/kg, 400 mg/kg) were used to evaluate in vivo activity. Methotrexate was used as the positive drug. H/E staining and micro-CT methods were used to monitor the pathological changes of CIA rats. ELISA method was used to assess the serum level of immune- and inflammation-related cytokines. Immunohistochemical experiments were used to test the gene expression in JAK and Nf-κB pathways. Results: 42 compounds were identified from PF. PF administration lowered the increased spleen index compared with that of control and MTX groups, and partially restored body weight, reduced paw swelling, and arthritis score compared with the model group. Macroscopic assessment indicated inflamed paw with significant swelling in the model group, while the extent of inflammation and swelling was attenuated by both MTX and PF. H/E staining experiments demonstrated that pathological changes of synovial cells and infiltration of inflammatory cells were observed in the model group. In contrast, the MTX and PF treatment partially reversed these pathological changes. Micro-CT examination showed severe injuries and scars caused by inflammation for the model group, and in the high-dosage group (400 mg/kg) the inflammation-caused injuries and scars were dramatically ameliorated. Mechanism study showed that PF restored Nf-κB phosphorylation and JAK2 expression compared with the model group. Conclusion: P. forrestii possesses a potent effect on CIA rats. Nf-κB and JAK2 pathways are involved in its protective effect on CIA.

Organic radicals driving polycyclic aromatic hydrocarbon polymerization with peracetic acid activation in soil.

The use of peracetic acid (PAA) in advanced oxidation processes has gained significant attention recently, but the knowledge of activating PAA to degrade polycyclic aromatic hydrocarbons (PAHs) is limited due to the variety and selectivity of reactive substances in PAA oxidation system. This paper presented the first systemically study on the degradation of PAHs by PAA activation in soil. It was found that heat-activated peracetic acid (heat/PAA) was capable of degrading phenanthrene (PHE) efficiently with degradation efficiency > 90 % within 30 min. Experimental results demonstrated that a series of reactive oxygen species (ROS) including organic radicals (RO•), hydroxyl radicals (HO•) and singlet oxygen (1O2) were generated, while acetylperoxyl (CH3C(O)OO•) and acetyloxyl (CH3C(O)O•) radicals were primarily responsible for PHE degradation in soil. Further analysis shows that polymerization products such as diphenic acid, 2'-formyl-2-biphenylcarboxylic acid and other macromolecules were dominant products of PHE degradation, suggesting polymerization driving PHE degradation instead of the conventional mineralization process. Toxicity analysis shows that most of the polymerization products had less toxicity than that of PHE. These results indicate that PAA activation was a highly effective remediation method for PAHs contaminated soil, which also provided a novel mechanism for pollutant degradation with the PAA activation process for environmental remediation.

[Carbon Footprint of Spent Ternary Lithium-Ion Battery Waste Recycling].

Road transport is the primary source of greenhouse gas emissions in China's transportation field. As an important means to achieve the "double carbon" goal in the transportation field, the new energy automobile industry will face a large number of power battery scrapping in the future. In order to quantitatively assess the carbon emission reduction benefits generated by the spent ternary lithium-ion battery waste recycling industry, the carbon footprint accounting model of spent ternary lithium-ion battery waste recycling and utilization was constructed from the life cycle perspective. By optimizing the power structure and transportation structure, the carbon emission reduction potential of spent ternary lithium-ion battery waste recycling was predicted and evaluated. In addition, the uncertainty analysis was conducted using the propagation of uncertainty equation to ensure the reliability and effectiveness of the carbon footprint results. The results showed that the current carbon footprint of Chinese enterprises using wet technology to recover 1 kg waste lithium batteries was -2 760.90 g (directional recycling process) and -3 752.78 g (recycling process), and the uncertainty of the carbon footprint was 16 % (directional recycling process) and 15 % (recycling process), respectively. From the analysis of carbon emission contribution, the regenerated product stage was the primary source of carbon reduction in the wet recycling and utilization of waste ternary lithium batteries, whereas the battery acquisition, disassembly, and end treatment stages were the main sources of carbon increase. Compared to optimizing the transportation structure, optimizing the power structure could effectively achieve greater carbon emission reduction potential. Under the collaborative optimization scenario, compared to that before optimization, 14 %-19 % carbon emission reduction could be achieved. Compared with native products, the directional circulation process and recycling process could achieve 9 % and 11 % emission reduction potential, respectively.

Targeted Modulation of Redox and Immune Homeostasis in Acute Lung Injury Using a Thioether-Functionalized Dendrimer.

Acute lung injury (ALI) is the pathophysiological precursor of acute respiratory distress syndrome. It is characterized by increased oxidative stress and exaggerated inflammatory response that disrupts redox reactions and immune homeostasis in the lungs, thereby posing significant clinical challenges. In this study, an internally functionalized thioether-enriched dendrimer Sr-G4-PEG is developed, to scavenge both proinflammatory cytokines and reactive oxygen species (ROS) and restore homeostasis during ALI treatment. The dendrimers are synthesized using an efficient and orthogonal thiol-ene "click" chemistry approach that involves incorporating thioether moieties within the dendritic architectures to neutralize the ROS. The ROS scavenging of Sr-G4-PEG manifests in its capacity to sequester proinflammatory cytokines. The synergistic effects of scavenging ROS and sequestering inflammatory cytokines by Sr-G4-PEG contribute to redox remodeling and immune homeostasis, along with the modulation of the NLRP3-pyroptosis pathway. Treatment with Sr-G4-PEG enhances the therapeutic efficacy of ALIs by alleviating alveolar bleeding, reducing inflammatory cell infiltration, and suppressing the release of inflammatory cytokines. These results suggest that Sr-G4-PEG is a potent nanotechnological candidate for remodeling redox and immune homeostasis in the treatment of ALIs, demonstrating the great potential of dendrimer-based nanomedicine for the treatment of respiratory pathologies.

Mapping the landscape of sleep medicine training across Asia.

STUDY OBJECTIVES: This study assessed the current state of sleep medicine accreditation and training in Asia by conducting a comprehensive survey across 29 Asian countries and regions facilitated by the Asian Society of Sleep Medicine (ASSM) to identify existing gaps and provide recommendations for future enhancements. METHODS: The ASSM Education Task Force Committee designed a survey to gather data on accreditation, education, and training standards in sleep medicine, including information on challenges in enhancing education in the field. RESULTS: With an 86% (25 countries/regions) response rate, the survey showed that sleep medicine is recognized as an independent specialty in just nine countries/regions (36% of the countries/regions surveyed). Ten countries/regions have established sleep medicine training programs, with Japan and Saudi Arabia offering it as a distinct specialty. Significant disparities in training and accreditation standards were identified, with many countries/regions lacking formalized training and practice guidelines. The survey also revealed that most local sleep societies across Asia support the development of an Asian Sleep Medicine Training Curriculum led by the ASSM. However, several barriers significantly impede the establishment and development of sleep medicine training programs, including the scarcity of trained specialists and technologists and the absence of national accreditation for sleep medicine. CONCLUSIONS: The survey highlights the need for standardized sleep medicine training and accreditation across Asia. Developing an Asian Sleep Medicine Training Curriculum and promoting ASSM accreditation guidelines are key recommendations. Implementing these strategies is essential for advancing sleep medicine as a widely recognized discipline throughout Asia.

Excess multi-cause mortality linked to influenza virus infection in China, 2012-2021: a population-based study.

Objectives: The aim of this study is to estimate the excess mortality burden of influenza virus infection in China from 2012 to 2021, with a concurrent analysis of its associated disease manifestations. Methods: Laboratory surveillance data on influenza, relevant population demographics, and mortality records, including cause of death data in China, spanning the years 2012 to 2021, were incorporated into a comprehensive analysis. A negative binomial regression model was utilized to calculate the excess mortality rate associated with influenza, taking into consideration factors such as year, subtype, and cause of death. Results: There was no evidence to indicate a correlation between malignant neoplasms and any subtype of influenza, despite the examination of the effect of influenza on the mortality burden of eight diseases. A total of 327,520 samples testing positive for influenza virus were isolated between 2012 and 2021, with a significant decrease in the positivity rate observed during the periods of 2012-2013 and 2019-2020. China experienced an average annual influenza-associated excess deaths of 201721.78 and an average annual excess mortality rate of 14.53 per 100,000 people during the research period. Among the causes of mortality that were examined, respiratory and circulatory diseases (R&C) accounted for the most significant proportion (58.50%). Fatalities attributed to respiratory and circulatory diseases exhibited discernible temporal patterns, whereas deaths attributable to other causes were dispersed over the course of the year. Conclusion: Theoretically, the contribution of these disease types to excess influenza-related fatalities can serve as a foundation for early warning and targeted influenza surveillance. Additionally, it is possible to assess the costs of prevention and control measures and the public health repercussions of epidemics with greater precision.

Associations of sex-related and thyroid-related hormones with risk of metabolic dysfunction-associated fatty liver disease in T2DM patients.

BACKGROUND: We aimed to examine sex-specific associations between sex- and thyroid-related hormones and the risk of metabolic dysfunction-associated fatty liver disease (MAFLD) in patients with type 2 diabetes mellitus (T2DM). METHODS: Cross-sectional analyses of baseline information from an ongoing cohort of 432 T2DM patients (185 women and 247 men) in Xiamen, China were conducted. Plasma sex-related hormones, including estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), progesterone, and total testosterone (TT), and thyroid-related hormones, including free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and parathyroid hormone (PTH), were measured using chemiluminescent immunoassays. MAFLD was defined as the presence of hepatic steatosis (diagnosed by either hepatic ultrasonography scanning or fatty liver index (FLI) score > 60) since all subjects had T2DM in the present study. RESULTS: Prevalence of MAFLD was 65.6% in men and 61.1% in women with T2DM (P = 0.335). For men, those with MAFLD showed significantly decreased levels of FSH (median (interquartile range (IQR)):7.2 (4.9-11.1) vs. 9.8 (7.1-12.4) mIU/ml) and TT (13.2 (10.4-16.5) vs. 16.7 (12.8-21.6) nmol/L) as well as increased level of FT3 (mean ± standard deviation (SD):4.63 ± 0.68 vs. 4.39 ± 0.85 pmol/L) than those without MAFLD (all p-values < 0.05). After adjusting for potential confounding factors, FSH and LH were negative, while progesterone was positively associated with the risk of MAFLD in men, and the adjusted odds ratios (ORs) (95% confidence intervals (CIs)) were 0.919 (0.856-0.986), 0.888 (0.802-0.983), and 8.069 (2.019-32.258) (all p-values < 0.05), respectively. In women, there was no statistically significant association between sex- or thyroid-related hormones and the risk of MAFLD. CONCLUSION: FSH and LH levels were negative, whereas progesterone was positively associated with the risk of MAFLD in men with T2DM. Screening for MAFLD and monitoring sex-related hormones are important for T2DM patients, especially in men.