Mechanisms of bacterial and fungal community assembly in leaf miners during transition from natural to laboratory environments.

Environmental heterogeneity partly drives microbial succession in arthropods, while the microbial assembly mechanisms during environmental changes remain largely unknown. Here, we explored the temporal dynamics and assembly mechanisms within both bacterial and fungal communities in Liriomyza huidobrensis (Blanchard) during the transition from field to laboratory conditions. We observed a decrease in bacterial diversity and complexity of bacterial-fungal co-occurrence networks in leaf miners transitioning from wild to captive environments. Both neutral and null models revealed that stochastic processes, particularly drift (contributing over 70%), play a crucial role in governing bacterial and fungal community assembly. The relative contribution of ecological processes such as dispersal, drift, and selection varied among leaf miners transitioning from wild to captive states. Furthermore, we propose a hypothetical scenario for the assembly and succession of microbial communities in the leaf miner during the short- and long-term transition from the wild to captivity. Our findings suggest that environmental heterogeneity determines the ecological processes governing bacterial and fungal community assembly in leaf miners, offering new insights into microbiome and mycobiome assembly mechanisms in invasive pests amidst environmental change.

GATIS score for predicting the prognosis of rectal neuroendocrine neoplasms: A Chinese multicenter study of 12-year experience.

BACKGROUND: There is currently a shortage of accurate, efficient, and precise predictive instruments for rectal neuroendocrine neoplasms (NENs). AIM: To develop a predictive model for individuals with rectal NENs (R-NENs) using data from a large cohort. METHODS: Data from patients with primary R-NENs were retrospectively collected from 17 large-scale referral medical centers in China. Random forest and Cox proportional hazard models were used to identify the risk factors for overall survival and progression-free survival, and two nomograms were constructed. RESULTS: A total of 1408 patients with R-NENs were included. Tumor grade, T stage, tumor size, age, and a prognostic nutritional index were important risk factors for prognosis. The GATIS score was calculated based on these five indicators. For overall survival prediction, the respective C-indexes in the training set were 0.915 (95% confidence interval: 0.866-0.964) for overall survival prediction and 0.908 (95% confidence interval: 0.872-0.944) for progression-free survival prediction. According to decision curve analysis, net benefit of the GATIS score was higher than that of a single factor. The time-dependent area under the receiver operating characteristic curve showed that the predictive power of the GATIS score was higher than that of the TNM stage and pathological grade at all time periods. CONCLUSION: The GATIS score had a good predictive effect on the prognosis of patients with R-NENs, with efficacy superior to that of the World Health Organization grade and TNM stage.

Global, regional, national epidemiology and trends of neglected tropical diseases in youths and young adults aged 15-39 years from 1990 to 2019: findings from the global burden of disease study 2019.

BACKGROUND: In recent years, the escalating concern for neglected tropical diseases (NTDs) has been recognized as a pressing global health issue. This concern is acutely manifested in low- and middle-income countries, where there is an escalating prevalence among adolescents and young adults. The burgeoning of these conditions threatens to impair patients' occupational capabilities and overall life quality. Despite the considerable global impact of NTDs, comprehensive studies focusing on their impact in younger populations remain scarce. Our study aims to describe the global prevalence of neglected tropical diseases among people aged 15 to 39 years over the 30-year period from 1990 to 2019, and to project the disease burden of the disease up to 2040. METHODS: Annual data on incident cases, mortality, and disability-adjusted life years (DALYs) for NTDs were procured from the Global Burden of Disease Study 2019 (GBD 2019). These data were stratified by global and regional distribution, country, social development index (SDI), age, and sex. We computed age-standardized rates (ASRs) and the numbers of incident cases, mortalities, and DALYs from 1990 to 2019. The estimated annual percentage change (EAPC) in the ASRs was calculated to evaluate evolving trends. RESULTS: In 2019, it was estimated that there were approximately 552 million NTD cases globally (95% Uncertainty Interval [UI]: 519.9 million to 586.3 million), a 29% decrease since 1990. South Asia reported the highest NTD prevalence, with an estimated 171.7 million cases (95% UI: 150.4 million to 198.6 million). Among the five SDI categories, the prevalence of NTDs was highest in the moderate and low SDI regions in 1990 (approximately 270.5 million cases) and 2019 (approximately 176.5 million cases). Sub-Saharan Africa recorded the most significant decline in NTD cases over the past three decades. Overall, there was a significant inverse correlation between the disease burden of NTDs and SDI. CONCLUSION: NTDs imposed over half a billion incident cases and 10.8 million DALYs lost globally in 2019-exerting an immense toll rivaling major infectious and non-communicable diseases. Encouraging declines in prevalence and disability burdens over the past three decades spotlight the potential to accelerate progress through evidence-based allocation of resources. Such strategic integration could substantially enhance public awareness about risk factors and available treatment options.

BACE1 inhibitors from the fruits of Alpinia oxyphylla have efficacy to treat T2DM-related cognitive disorder.

The fruits of Alpinia oxyphylla (Alpiniae Oxyphyllae Fructus, AOF) are one of the "Four Famous South Medicines" in China. In this study, beta-site amyloid protein precursor cleaving enzyme 1 (BACE1) was applied to explore the active components in AOF responsible for type 2 diabetes mellitus (T2DM)-related cognitive disorder. As a result, 24 compounds including three unreported ones (1, 3, 4) were isolated from AOF. Compound 1 is an unusual carbon­carbon linked diarylheptanoid dimer, and compound 4 is the first case of 3,4-seco-eudesmane sesquiterpenoid with a 5/6-bicyclic skeleton. Four diarylheptanoids (3, 5-7), one flavonoid (9) and two sesquiterpenoids (14 and 20) showed BACE1 inhibitory activity, of which the most active 6 was revealed to be a non-competitive and anti-competitive mixed inhibitor. Docking simulation suggested that OH-4' of 6 played important roles in maintaining activity by forming hydrogen bonds with Ser36 and Ile126 residues. Compounds 3, 5, 9 and 20 displayed neuroprotective effects against amyloid ß (Aß)-induced damage in BV2 cells. Mechanism study revealed that compounds 5 and 20 downregulated the expression of BACE1 and upregulated the expression of Lamp2 to exert effects. Thus, the characteristic diarylheptanoids and sesquiterpenoids in AOF had the efficacy to alleviate T2DM-related cognitive disorder by inhibiting BACE1 activity and reversing Aß-induced neuronal damage.

Does type 1 diabetes serve as a protective factor against inflammatory bowel disease: A Mendelian randomization study.

BACKGROUND: The impact of type 1 diabetes (T1D) on inflammatory bowel disease (IBD) remains unclear. AIM: To analyze the causal relationship between T1D and IBD using Mendelian ran-domization (MR). METHODS: Single nucleotide polymorphisms were sourced from FinnGen for T1D, IBD, ulcerative colitis (UC) and Crohn's disease (CD). Inverse variance-weighted, MR-Egger, and weighted median tests were used to assess exposure-outcome causality. The MR-Egger intercept was used to assess horizontal pleiotropy. Co-chran's Q and leave-one-out method were used to analyze heterogeneity and sensitivity, respectively. RESULTS: Our MR analysis indicated that T1D was associated with a reduced risk of IBD [odds ratio (OR): 0.959; 95% confidence interval (CI): 0.938-0.980; P < 0.001] and UC (OR: 0.960; 95%CI: 0.929-0.992; P = 0.015), with no significant association observed in terms of CD risk (OR: 0.966; 95%CI: 0.913-1.022; P = 0.227). The MR-Egger intercept showed no horizontal pleiotropy (P > 0.05). Cochran's Q and leave-one-out sensitivity analyses showed that the results were not heterogeneous (P > 0.05) and were robust. CONCLUSION: This MR analysis suggests that T1D serves as a potential protective factor against IBD and UC but is independent of CD.

Promoting the healing of infected diabetic wound by nanozyme-containing hydrogel with anti-bacterial inflammation suppressing, ROS-scavenging and oxygen-generating properties.

Bacterial infections already pose a significant threat to skin wounds, especially in diabetic patients who have difficulty healing wounds. However, wound or bacterial infections are known to produce excess reactive oxygen species (ROS), and hypoxia may further hinder wound healing and the development of chronic wounds. In this study, a multifunctional hydrogel for ROS scavenging and bacterial inhibition was developed by cross-linking polyvinyl alcohol (PVA) and sodium alginate (SA) with graphene oxide (GO) loaded with silver-platinum hybrid nanoparticles (GO@Ag-Pt). The PVA/SA hydrogel loaded with GO@Ag-Pt exhibited the ability to scavenge different types of ROS, generate O2, and kill a broad spectrum of bacteria in vitro. The silver-platinum hybrid nanoparticles significantly increased the antibacterial ability against Escherichia coli and Staphylococcus aureus compared with silver nanoparticles (AgNps). GO@Ag-Pt loaded hydrogel was effective in treating infections caused by S.aureus, thereby significantly promoting wound healing during the inflammatory phase. Hydrogel therapy significantly reduced the level of ROS and alleviated inflammation levels. Notably, our ROS-scavenging, antibacterial hydrogels can be used to effectively treat various types of wounds, including difficult-to-heal diabetic wounds with bacterial infections. Thus, this study proposes an effective strategy for various chronic wound healing based on ROS clearance and bacteriostatic hydrogels.

Enhanced Visible-Light-Driven Photocatalytic Overall Splitting of Pure Water in a Porous Microreactor.

Photocatalytic overall splitting of pure water (H2O) without sacrificial reagent to hydrogen (H2) and oxygen (O2) holds a great potential for achieving carbon neutrality. Herein, by anchoring cobalt sulfide (Co9S8) as cocatalyst and cadmium sulfide (CdS) as light absorber to channel wall of a porous polymer microreactor (PP12), continuous violent H2 and O2 bubbling productions from photocatalytic overall splitting of pure H2O without sacrificial reagent is achieved, with H2 and O2 production rates as high as 4.41 and 2.20 mmol h-1 gcat.-1 respectively. These are significantly enhanced than those in the widely used stirred tank-type reactor in which no O2 is produced and H2 production rate is only 0.004 mmol h-1 gcat.-1. Besides improved charge separation and interaction of H2O with photocatalyst in PP12, bonding interaction of Co9S8 with PP12 creates abundant catalytic active sites for simultaneous productions of H2 and O2, thus leading to the significantly enhanced H2 and O2 bubbling productions in PP12. This offers a new strategy to enhance photocatalytic overall splitting of pure H2O without sacrificial reagent.

A thalamic nucleus reuniens-lateral septum-lateral hypothalamus circuit for comorbid anxiety-like behaviors in chronic itch.

Chronic itch often clinically coexists with anxiety symptoms, creating a vicious cycle of itch-anxiety comorbidities that are difficult to treat. However, the neuronal circuit mechanisms underlying the comorbidity of anxiety in chronic itch remain elusive. Here, we report anxiety-like behaviors in mouse models of chronic itch and identify γ-aminobutyric acid-releasing (GABAergic) neurons in the lateral septum (LS) as the key player in chronic itch-induced anxiety. In addition, chronic itch is accompanied with enhanced activity and synaptic plasticity of excitatory projections from the thalamic nucleus reuniens (Re) onto LS GABAergic neurons. Selective chemogenetic inhibition of the Re → LS circuit notably alleviated chronic itch-induced anxiety, with no impact on anxiety induced by restraint stress. Last, GABAergic neurons in lateral hypothalamus (LH) receive monosynaptic inhibition from LS GABAergic neurons to mediate chronic itch-induced anxiety. These findings underscore the potential significance of the Re → LS → LH pathway in regulating anxiety-like comorbid symptoms associated with chronic itch.

New species and new records of Laccaria (Agaricales, Basidiomycota) from Northern Thailand.

Two new species Laccariapseudoalba and L.subroseoalbescens are described and illustrated, based on morphological characteristics and molecular phylogenetic analysis. Two new records, Laccariaumbilicata and L.yunnanensis from Thailand, are also reported. Laccariasubroseoalbescens is characterized by small basidiomata, stipe equal with an enlarged base, and nearly subclavate, pale pink to light orange. Laccariapseudoalba is characterized by pale orange to orange white pileus, has umbo when young on the pileus, and fistulose stipe of the pale to pastel red color. Phylogenetic analysis based on sequence data from rDNA internal transcribed spacer ITS1-5.8S-ITS2 rDNA (ITS), nuc 28S rDNA (28S), RNA polymerase II subunit 2 (rpb2), and translation elongation factor 1-α (tef1-α) are provided as further evidence. Molecular analysis confirms the phylogenetic positions of the two new species and two new records. The differences in characteristics of these two new species and closely related species are discussed herein.

Reduction of eEF2 kinase alleviates the learning and memory impairment caused by acrylamide.

BACKGROUND: The impact of acrylamide (ACR) on learning and memory has garnered considerable attention. However, the targets and mechanisms are still unclear. RESULTS: Elongation factor 2 (eEF2) was significantly upregulated in the results of serum proteomics. Results from in vitro and in vivo experiments indicated a notable upregulation of Eukaryotic elongation factor 2 kinase (eEF2K), the sole kinase responsible for eEF2 phosphorylation, following exposure to ACR (P < 0.05). Subsequent in vitro experiments using eEF2K siRNA and in vivo experiments with eEF2K-knockout mice demonstrated significant improvements in abnormal indicators related to ACR-induced learning and memory deficits (P < 0.05). Proteomic analysis of the hippocampus revealed Lpcat1 as a crucial downstream protein regulated by eEF2K. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated that eEF2K may play a role in the process of ACR-induced learning and memory impairment by affecting ether lipid metabolism. CONCLUSIONS: In summary, eEF2K as a pivotal treatment target in the mechanisms underlying ACR-induced learning and memory impairment, and studies have shown that it provides robust evidence for potential clinical interventions targeting ACR-induced impairments.

Recurrent spinal subdural hematoma following percutaneous kyphoplasty: A unique case report.

Spinal intradural (subdural and subarachnoid) hematoma following percutaneous kyphoplasty is an extremely rare complication. In this report, we described a case of 2 episodes of subarachnoid hemorrhage with delayed paralysis after kyphoplasty. A 73-year-old man underwent percutaneous kyphoplasty in our hospital an osteoporotic vertebral fracture at the T12 level. On the 55 h after kyphoplasty for T12 osteoporotic vertebral fracture, he developed paralysis of the lower limbs. An emergency posterior decompression from T8 to L2 was performed. And the subarachnoid hematomas were removed. Postoperatively, the neurological symptoms improved rapidly. However, 2 weeks after the operation, the patient experienced a setback with severe neurological decline (paraplegia with sensory and autonomic dysfunction). An emergency posterior decompression from T5 to L2 was performed. The subarachnoid hematomas were removed. This case reflects the cause and progression of spinal subdural hematoma. Previous literature has debated the best treatment approach for spinal subarachnoid hemorrhage, but the prognosis of patients is heavily dependent on precise symptom evaluation and localization.

Photoinduced Co/Ni-cocatalyzed Markovnikov hydroarylation of unactivated olefins with aryl bromides.

Transition-metal-catalyzed hydroarylation of unactivated alkenes via metal hydride hydrogen atom transfer (MHAT) is an attractive approach for the construction of C(sp2)-C(sp3) bonds. However, this kind of reaction focuses mainly on using reductive hydrosilane as a hydrogen donor. Here, a novel photoinduced Co/Ni-cocatalyzed Markovnikov hydroarylation of unactivated alkenes with aryl bromides using protons as a hydrogen source has been developed. This reaction represents the first example of photoinduced MHAT via a reductive route intercepting an organometallic coreactant. The key to this transformation was that the CoIII-H species was generated from the protonation of the CoI intermediate, and the formed CoIII-C(sp3) intermediate interacted with the organometallic coreactant rather than reacting with nucleophiles, a method which has been well developed in photoinduced Co-catalyzed MHAT reactions. This reaction is characterized by its high catalytic efficiency, construction of quaternary carbons, simple reaction conditions and expansion of the reactive mode of Co-catalyzed MHAT reactions via a reductive route. Moreover, this catalytic system could also be applied to complex substrates derived from glycosides.

Light-Induced 1,3-Thiosulfonylation of ß,γ-Unsaturated Ketones with Thiosulfonates.

Sulfur-containing compounds exhibit potent significance in drug molecules. Thiosulfonates as 1,3-thiosulfonylation reactants to olefins have yet to be investigated. Herein, we report photoinduced 1,3-difunctionalization of ß,γ-unsaturated ketones with thiosulfonates, which undergo a radical 1,2-acyl shift. The protocol features mild conditions, high regioselectivity, and 100% atom economy.

Prediction of non-muscle invasive bladder cancer recurrence using deep learning of pathology image.

We aimed to build a deep learning-based pathomics model to predict the early recurrence of non-muscle-infiltrating bladder cancer (NMIBC) in this work. A total of 147 patients from Xuzhou Central Hospital were enrolled as the training cohort, and 63 patients from Suqian Affiliated Hospital of Xuzhou Medical University were enrolled as the test cohort. Based on two consecutive phases of patch level prediction and WSI-level predictione, we built a pathomics model, with the initial model developed in the training cohort and subjected to transfer learning, and then the test cohort was validated for generalization. The features extracted from the visualization model were used for model interpretation. After migration learning, the area under the receiver operating characteristic curve for the deep learning-based pathomics model in the test cohort was 0.860 (95% CI 0.752-0.969), with good agreement between the migration training cohort and the test cohort in predicting recurrence, and the predicted values matched well with the observed values, with p values of 0.667766 and 0.140233 for the Hosmer-Lemeshow test, respectively. The good clinical application was observed using a decision curve analysis method. We developed a deep learning-based pathomics model showed promising performance in predicting recurrence within one year in NMIBC patients. Including 10 state prediction NMIBC recurrence group pathology features be visualized, which may be used to facilitate personalized management of NMIBC patients to avoid ineffective or unnecessary treatment for the benefit of patients.

Global, regional, and national burden of ischemic stroke, 1990-2021: an analysis of data from the global burden of disease study 2021.

Background: Ischemic stroke remains a major contributor to global mortality and morbidity. This study aims to provide an updated assessment of rates in ischemic stroke prevalence, incidence, mortality, and disability-adjusted life-years (DALYs) from 1990 to 2021, specifically focusing on including prevalence investigation alongside other measures. The analysis is stratified by sex, age, and socio-demographic index (SDI) at global, regional, and national levels. Methods: Data for this study was obtained from the 2021 Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). To quantify temporal patterns and assess trends in age-standardized rates of ischemic stroke prevalence (ASPR), incidence (ASIR), mortality (ASDR), and DALYs, estimated annual percentage changes (EAPCs) were computed over the study period. The analyses were disaggregated by gender, 20 age categories, 21 GBD regions, 204 nations/territories, and 5 SDI quintiles. R statistical package V 4.4.2 was performed for statistical analyses and plot illustrations. Findings: In 2021, the global burden of ischemic stroke remained substantial, with a total of 69,944,884.8 cases with an ASPR of 819.5 cases per 100,000 individuals (95% UI: 760.3-878.7). The ASIR was 92.4 per 100,000 people (95% UI: 79.8-105.8), while the ASDR was 44.2 per 100,000 persons (95% UI: 39.3-47.8). Additionally, the age-standardized DALY rate was 837.4 per 100,000 individuals (95% UI: 763.7-905). Regionally, areas with high-middle SDI exhibited the greatest ASPR, ASIR, ASDR, and age-standardized DALY rates, whereas high SDI regions had the lowest rates. Geospatially, Southern Sub-Saharan Africa had the highest ASPR, while Eastern Europe showed the highest ASIR. The greatest ASDR and age-standardized DALY rates were observed in Eastern Europe, Central Asia, as well as North Africa, and the Middle East. Among countries, Ghana had the highest ASPR, and North Macedonia had both the highest ASIR and ASDR. Furthermore, North Macedonia also exhibited the highest age-standardized DALY rate. Interpretation: Regions with high-middle and middle SDI continued to experience elevated ASPR, ASIR, ASDR and age-standardized DALY rates. The highest ischemic stroke burden was observed in Southern Sub-Saharan Africa, Central Asia, Eastern Europe, and the Middle East. Funding: None.

Global, regional, and national burden and trends of migraine among youths and young adults aged 15-39 years from 1990 to 2021: findings from the global burden of disease study 2021.

BACKGROUND: Migraine, a widespread neurological condition, substantially affects the quality of life, particularly for adolescents and young adults. While its impact is significant, there remains a paucity of comprehensive global research on the burden of migraine in younger demographics. Our study sought to elucidate the global prevalence, incidence, and disability-adjusted life-years (DALYs) associated with migraine in the 15-39 age group from 1990 to 2021, utilizing data from the Global Burden of Disease (GBD) 2021 study. METHODS: Our comprehensive study analyzed migraine data from the GBD 2021 report, examining the prevalence, incidence, and DALYs across 204 countries and territories over a 32-year span. We stratified the information by age, sex, year, geographical region, and Socio-demographic Index (SDI). To evaluate temporal trends in these metrics, we employed the estimated annual percentage change (EAPC) calculation. RESULTS: Between 1990 and 2021, the worldwide prevalence of migraine among 15-39 year-olds increased substantially. By 2021, an estimated 593.8 million cases were reported, representing a 39.52% rise from 425.6 million cases in 1990. Global trends showed increases in age-standardized prevalence rate, incidence rate, and DALY rate for migraine during this period. The EAPC were positive for all three metrics: 0.09 for ASPR, 0.03 for ASIR, and 0.09 for DALY rate. Regions with medium SDI reported the highest absolute numbers of prevalent cases, incident cases, and DALYs in 2021. However, high SDI regions demonstrated the most elevated rates overall. Across the globe, migraine prevalence peaked in the 35-39 age group. Notably, female rates consistently exceeded male rates across all age categories. CONCLUSION: The global impact of migraine on youths and young adults has grown considerably from 1990 to 2021, revealing notable variations across SDI regions, countries, age groups, and sexes. This escalating burden necessitates targeted interventions and public health initiatives, especially in areas and populations disproportionately affected by migraine.

Connectomic insights into the impact of 1p/19q co-deletion in dominant hemisphere insular glioma patients.

Objectives: This study aimed to elucidate the influences of 1p/19q co-deletion on structural connectivity alterations in patients with dominant hemisphere insular diffuse gliomas. Methods: We incorporated 32 cases of left insular gliomas and 20 healthy controls for this study. Using diffusion MRI, we applied correlational tractography, differential tractography, and graph theoretical analysis to explore the potential connectivity associated with 1p/19q co-deletion. Results: The study revealed that the quantitative anisotropy (QA) of key deep medial fiber tracts, including the anterior thalamic radiation, superior thalamic radiation, fornix, and cingulum, had significant negative associations with 1p/19q co-deletion (FDR = 4.72 × 10-5). These tracts are crucial in maintaining the integrity of brain networks. Differential analysis further supported these findings (FWER-corrected p < 0.05). The 1p/19q non-co-deletion group exhibited significantly higher clustering coefficients (FDR-corrected p < 0.05) and reduced betweenness centrality (FDR-corrected p < 0.05) in regions around the tumor compared to HC group. Graph theoretical analysis indicated that non-co-deletion patients had increased local clustering and decreased betweenness centrality in peritumoral brain regions compared to co-deletion patients and healthy controls (FDR-corrected p < 0.05). Additionally, despite not being significant through correction, patients with 1p/19q co-deletion exhibited lower trends in weighted average clustering coefficient, transitivity, small worldness, and global efficiency, while showing higher tendencies in weighted path length compared to patients without the co-deletion. Conclusion: The findings of this study underline the significant role of 1p/19q co-deletion in altering structural connectivity in insular glioma patients. These alterations in brain networks could have profound implications for the neural functionality in patients with dominant hemisphere insular gliomas.

Global, regional, and national burden of HIV-negative tuberculosis, 1990-2021: findings from the Global Burden of Disease Study 2021.

BACKGROUND: Tuberculosis (TB) is a major infectious disease with significant public health implications. Its widespread transmission, prolonged treatment duration, notable side effects, and high mortality rate pose severe challenges. This study examines the epidemiological characteristics of TB globally and across major regions, providing a scientific basis for enhancing TB prevention and control measures worldwide. METHODS: The ecological study used data from the Global Burden of Disease (GBD) Study 2021. It assessed new incidence cases, deaths, disability-adjusted life years (DALYs), and trends in age-standardized incidence rates (ASIRs), mortality rates (ASMRs), and DALY rates for drug-susceptible tuberculosis (DS-TB), multidrug-resistant tuberculosis (MDR-TB), and extensively drug-resistant tuberculosis (XDR-TB) from 1990 to 2021. A Bayesian age-period-cohort model was applied to project ASIR and ASMR. RESULTS: In 2021, the global ASIR for all HIV-negative TB was 103.00 per 100,000 population [95% uncertainty interval (UI): 92.21, 114.91 per 100,000 population], declining by 0.40% (95% UI: - 0.43, - 0.38%) compared to 1990. The global ASMR was 13.96 per 100,000 population (95% UI: 12.61, 15.72 per 100,000 population), with a decline of 0.44% (95% UI: - 0.61, - 0.23%) since 1990. The global age-standardized DALY rate for HIV-negative TB was 580.26 per 100,000 population (95% UI: 522.37, 649.82 per 100,000 population), showing a decrease of 0.65% (95% UI: - 0.69, - 0.57 per 100,000 population) from 1990. The global ASIR of MDR-TB has not decreased since 2015, instead, it has shown a slow upward trend in recent years. The ASIR of XDR-TB has exhibited significant increase in the past 30 years. The projections indicate MDR-TB and XDR-TB are expected to see significant increases in both ASIR and ASMR from 2022 to 2035, highlighting the growing challenge of drug-resistant TB. CONCLUSIONS: This study found that the ASIR of MDR-TB and XDR-TB has shown an upward trend in recent years. To reduce the TB burden, it is essential to enhance health infrastructure and increase funding in low-SDI regions. Developing highly efficient, accurate, and convenient diagnostic reagents, along with more effective therapeutic drugs, and improving public health education and community engagement, are crucial for curbing TB transmission.

Anthocyanins-rich cranberry extract attenuates DSS-induced IBD in an intestinal flora independent manner.

Cranberry is abundantly rich in anthocyanins, a type of flavonoid with potent antioxidant properties and the resistance against certain diseases. In this study, anthocyanin-rich cranberry extract was extracted, purified, and its components were analyzed. 92.18 % of anthocyanins was obtained and the total content of anthocyanins was 302.62 mg/g after AB-8 resin purification. Quantification analysis showed that the extract mainly contained cyanidin-3-galactoside, procyanidin B2 and procyanidin B4. Then we explored its effects on dextran sulfate sodium (DSS)-induced inflammatory bowel disease (IBD) in mice. The supplementation of cranberry extract resulted in an alleviation of IBD symptoms, evidenced by improvements in the disease activity index (DAI), restoration of colon length and colonic morphology. Cranberry extract reversed the elevated iron and malondialdehyde (MDA) levels and restored glutathione (GSH) levels in IBD mice. Further analysis revealed that cranberry modulated ferroptosis-associated genes and reduced expression of pro-inflammatory cytokines. Although cranberry influenced the intestinal flora balance by reducing Proteobacteria and Escherichia-Shigella, and increasing Lactobacillus, as well as enhancing SCFAs content, these effects were not entirely dependent on intestinal flora modulation, as indicated by antibiotic intervention and fecal microbiota transplantation (FMT) experiments. In conclusion, our findings suggest that the beneficial impact of cranberry extract on IBD may primarily involve the regulation of colonic ferroptosis, independent of significant alterations in intestinal flora.

Palladium-catalyzed decarboxylative (4 + 3) cycloadditions of bicyclobutanes with 2-alkylidenetrimethylene carbonates for the synthesis of 2-oxabicyclo[4.1.1]octanes.

While cycloaddition reactions of bicyclobutanes (BCBs) have emerged as a potent method for synthesizing (hetero-)bicyclo[n.1.1]alkanes (usually n ≤ 3), their utilization in the synthesis of bicyclo[4.1.1]octane derivatives (BCOs) is still underdeveloped. Here, a palladium-catalyzed formal (4 + 3) reaction of BCBs with 1,4-O/C dipole precursors for the synthesis of oxa-BCOs is described. Unlike previous catalytic polar (3 + X) cycloadditions of BCBs, which are typically achieved through the activation of BCB substrates, the current reaction represents a novel strategy for realizing the cycloaddition of BCBs through the activation of the "X" cycloaddition partner. Moreover, the obtained functionalized oxa-BCOs products can be readily modified through various synthetic transformations.