Effect of long-acting PEGylated growth hormone for catch-up growth in children with idiopathic short stature: a 2-year real-world retrospective cohort study.

Several evidence gaps exist regarding the use of long-acting polyethylene glycol recombinant human growth hormone (PEG-rhGH) in children with idiopathic short stature (ISS), particularly studies conducted in real-world settings, with long-term follow-up, involving varied dosing regimens, and in comparison with daily rhGH. The study aimed to evaluate the effectiveness, safety, and adherence of once-weekly PEG-rhGH for catch-up growth in children with prepubertal ISS compared to daily rhGH. A real-world retrospective cohort study was conducted in prepubertal children with ISS in China. Children who voluntarily received once-weekly PEG-rhGH or daily rhGH were included and were followed up for 2 years. Ninety-five children were included, 47 received PEG-rhGH 0.2-0.3 mg/kg weekly and 48 received daily rhGH. Outcome measures included effectiveness in catch-up growth, adverse events, and treatment adherence. Height velocity increased significantly in both groups during rhGH therapy. In children who received PEG-rhGH treatment, height velocity was 10.59 ± 1.37 cm/year and 8.75 ± 0.86 cm/year in the first and second year, respectively, which were significantly more than those who received daily rhGH (9.80 ± 1.05 cm/year, P = 0.002, and 8.03 ± 0.89 cm/year, P < 0.001). The height standard deviation score improved at the end of the second year for all children (P < 0.001). However, children who received PEG-rhGH showed more excellent improvement than those with daily rhGH (1.65 ± 0.38 vs. 1.50 ± 0.36, P = 0.001). In children who received PEG-rhGH, lower missed doses were observed than those with daily rhGH (0.75 ± 1.06 vs. 4.4 ± 2.0, P < 0.001). No serious adverse events were observed. CONCLUSION: PEG-rhGH demonstrated superior effectiveness and adherence compared to daily rhGH in the treatment of children with ISS. The safety profiles were similar between the two treatments. WHAT IS KNOWN: • Recombinant human growth hormone (rhGH) has been used to increase adult height in children with idiopathic short stature (ISS), and its safety profile is comparable to other indications for growth hormone treatment. • The use of long-acting rhGH in children with ISS is still an area of uncertainty. WHAT IS NEW: • This 2-year real-world study provides new evidence that PEGylated rhGH (PEG-rhGH) is more effective than daily rhGH in promoting catch-up growth in children with ISS. • PEG-rhGH also demonstrated superior treatment adherence compared to daily rhGH in children with ISS. • The safety profiles of PEG-rhGH and daily rhGH were found to be similar.

Hyperglycemia-induced oxidative stress exacerbates mitochondrial apoptosis damage to cochlear stria vascularis pericytes via the ROS-mediated Bcl-2/CytC/AIF pathway.

OBJECTIVES: Diabetes is closely linked to hearing loss, yet the exact mechanisms remain unclear. Cochlear stria vascularis and pericytes (PCs) are crucial for hearing. This study investigates whether high glucose induces apoptosis in the cochlear stria vascularis and pericytes via elevated ROS levels due to oxidative stress, impacting hearing loss. METHODS: We established a type II diabetes model in C57BL/6J mice and used auditory brainstem response (ABR), Evans blue staining, HE staining, immunohistochemistry, and immunofluorescence to observe changes in hearing, blood-labyrinth barrier (BLB) permeability, stria vascularis morphology, and apoptosis protein expression. Primary cultured stria vascularis pericytes were subjected to high glucose, and apoptosis levels were assessed using flow cytometry, Annexin V-FITC, Hoechst 33342 staining, Western blot, Mitosox, and JC-1 probes. RESULTS: Diabetic mice showed decreased hearing thresholds, reduced stria vascularis density, increased oxidative stress, cell apoptosis, and decreased antioxidant levels. High glucose exposure increased apoptosis and ROS content in pericytes, while mitochondrial membrane potential decreased, with AIF and cytochrome C (CytC) released from mitochondria to the cytoplasm. Adding oxidative scavengers reduced AIF and CytC release, decreasing pericyte apoptosis. DISCUSSION: Hyperglycemia may induce mitochondrial apoptosis of cochlear stria vascularis pericytes through oxidative stress.

A Prognostic Model Based on Nutritional Indexes for Patients With Pan-Cancer: A Real-World Cohort Study.

BACKGROUND: The aim was to identify the nutritional indexes, construct a prognostic model, and develop a nomogram for predicting individual survival probability in pan-cancers. METHODS: Nutritional indicators, clinicopathological characteristics, and previous major treatment details of the patients were collected. The enrolled patients were randomly divided into training and validation cohorts. Least absolute shrinkage and selection operator (Lasso) regression cross-validation was used to determine the variables to include in the cox regression model. The training cohort was used to build the prediction model, and the validation cohort was used to further verify the discrimination, calibration, and clinical effectiveness of the model. RESULTS: A total of 2020 patients were included. The median OS was 56.50 months (95% CI, 50.36-62.65 months). In the training cohort of 1425 patients, through Lasso regression cross-validation, 13 characteristics were included in the model. Cox proportional hazards model was developed and visualized as a nomogram. The C-indexes of the model for predicting 1-, 3-, 5-, and 10-year OS were 0.848, 0.826, 0.814, and 0.799 in the training cohort and 0.851, 0.819, 0.814, and 0.801 in the validation cohort. The model showed great calibration in the two cohorts. Patients with a score of less than 274.29 had a better prognosis (training cohort: HR, 6.932; 95% CI, 5.723-8.397; log-rank p < 0.001; validation cohort: HR, 8.429; 95% CI, 6.180-11.497; log-rank p < 0.001). CONCLUSION: The prognostic model based on the nutritional indexes of pan-cancer can divide patients into different survival risk groups and performed well in the validation cohort.

HCR-Assisted RTF-EXPAR-Based Lateral Flow Analysis for Sensitive Detection of H1N1 Influenza Virus.

The H1N1 influenza virus is a significant pathogen responsible for seasonal influenza, and its frequent outbreaks pose substantial challenges to global public health. The present study successfully developed a lateral flow analysis platform that integrates reverse transcription-free exponential amplification reaction (RTF-EXPAR) and hybridization chain reaction (HCR) processes with functionalized quantum dots for the direct detection of H1N1 influenza virus RNA, eliminating the need for reverse transcription. The fluorescence signal on the band recorded with a smartphone can be utilized for the quantitative determination of the target. Interestingly, the dual signal amplification strategy exhibits high sensitivity with a remarkably low detection limit of 10 aM. Moreover, this platform exhibits excellent flexibility and universality, where the various pathogens can be determined by replacing the specific nucleic acid fragments in RTF-EXPAR. The aforementioned advantages reveal its huge potential in the early diagnosis of H1N1 influenza virus infection and developing point-of-care testing (POCT) equipment for nucleic acid analysis.

Seasonal and Spatial Fluctuations of Reactive Oxygen Species in Riparian Soils and Their Contributions on Organic Carbon Mineralization.

Reactive oxygen species (ROS) are ubiquitous in the natural environment and play a pivotal role in biogeochemical processes. However, the spatiotemporal distribution and production mechanisms of ROS in riparian soil remain unknown. Herein, we performed uninterrupted monitoring to investigate the variation of ROS at different soil sites of the Weihe River riparian zone throughout the year. Fluorescence imaging and quantitative analysis clearly showed the production and spatiotemporal variation of ROS in riparian soils. The concentration of superoxide (O2•-) was 300% higher in summer and autumn compared to that in other seasons, while the highest concentrations of 539.7 and 20.12 µmol kg-1 were observed in winter for hydrogen peroxide (H2O2) and hydroxyl radicals (•OH), respectively. Spatially, ROS production in riparian soils gradually decreased along with the stream. The results of the structural equation and random forest model indicated that meteorological conditions and soil physicochemical properties were primary drivers mediating the seasonal and spatial variations in ROS production, respectively. The generated •OH significantly induced the abiotic mineralization of organic carbon, contributing to 17.5-26.4% of CO2 efflux. The obtained information highlighted riparian zones as pervasive yet previously underestimated hotspots for ROS production, which may have non-negligible implications for carbon turnover and other elemental cycles in riparian soils.

Quercetin attenuates cisplatin-induced mitochondrial apoptosis via PI3K/Akt mediated inhibition of oxidative stress in pericytes and improves the blood labyrinth barrier permeability.

Cisplatin (CDDP) is broadly employed to treat different cancers, whereas there are no drugs approved by the Food and Drug Administration (FDA) for preventing its side effects, including ototoxicity. Quercetin (QU) is a widely available natural flavonoid compound with anti-tumor and antioxidant properties. The research was designed to explore the protective effects of QU on CDDP-induced ototoxicity and its underlying mechanisms in male C57BL/6 J mice and primary cultured pericytes (PCs). Hearing changes, morphological changes of stria vascularis, blood labyrinth barrier (BLB) permeability and expression of apoptotic proteins were observed in vivo by using the auditory brainstem response (ABR) test, HE staining, Evans blue staining, immunohistochemistry, western blotting, etc. Oxidative stress levels, mitochondrial function and endothelial barrier changes were observed in vitro by using DCFH-DA probe detection, flow cytometry, JC-1 probe, immunofluorescence and the establishment in vitro BLB models, etc. QU pretreatment activates the PI3K/AKT signaling pathway, inhibits CDDP-induced oxidative stress, protects mitochondrial function, and reduces mitochondrial apoptosis in PCs. However, PI3K/AKT specific inhibitor (LY294002) partially reverses the protective effects of QU. In addition, in vitro BLB models were established by coculturing PCs and endothelial cells (ECs), which suggests that QU both reduces the CDDP-induced apoptosis in PCs and improves the endothelial barrier permeability. On the whole, the research findings suggest that QU can be used as a novel treatment to reduce CDDP-induced ototoxicity.

Crop bioengineering via gene editing: reshaping the future of agriculture.

Genome-editing technologies have revolutionized research in plant biology, with major implications for agriculture and worldwide food security, particularly in the face of challenges such as climate change and increasing human populations. Among these technologies, clustered regularly interspaced short palindromic repeats [CRISPR]-CRISPR-associated protein [Cas] systems are now widely used for editing crop plant genomes. In this review, we provide an overview of CRISPR-Cas technology and its most significant applications for improving crop sustainability. We also review current and potential technological advances that will aid in the future breeding of crops to enhance food security worldwide. Finally, we discuss the obstacles and challenges that must be overcome to realize the maximum potential of genome-editing technologies for future crop and food production.

Analysis of the role of PANoptosis in seizures via integrated bioinformatics analysis and experimental validation.

Background: Epilepsy is recognized as the most common chronic neurological condition among children, and hippocampal neuronal cell death has been identified as a crucial factor in the pathophysiological processes underlying seizures. In recent studies, PANoptosis, a newly characterized form of cell death, has emerged as a significant contributor to the development of various neurological disorders, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. PANoptosis involves the simultaneous activation of pyroptosis, apoptosis, and necroptosis within the same population of cells. However, its specific role in the context of seizures remains to be fully elucidated. Further investigation is required to uncover the precise involvement of PANoptosis in the pathogenesis of seizures and to better understand its potential implications for the development of targeted therapeutic approaches in epilepsy. Methods: In this study, the gene expression data of the hippocampus following the administration of kainic acid (KA) or NaCl was obtained from the Gene Expression Omnibus (GEO) database. The PANoptosis-related gene set was compiled from the GeneCards database and previous literature. Time series analysis was performed to analyze the temporal expression patterns of the PANoptosis-related genes. Gene set variation analysis (GSVA), Gene ontology (GO), and Kyoto encyclopedia of genes and genomes (KEGG) were employed to explore potential biological mechanisms underlying PANoptosis and its role in seizures. Weighted gene co-expression network analysis (WGCNA) and differential expression analysis were utilized to identify pivotal gene modules and PANoptosis-related genes associated with the pathophysiological processes underlying seizures. To validate the expression of PANoptosis-related genes, Western blotting or quantitative real-time polymerase chain reaction (qRT-PCR) assays were conducted. These experimental validations were performed in human blood samples, animal models, and cell models to verify the expression patterns of the PANoptosis-related genes and their relevance to epilepsy. Results: The GSVA analysis performed in this study demonstrated that PANoptosis-related genes have the potential to distinguish between the control group and KA-induced epileptic mice. This suggests that the expression patterns of these genes are significantly altered in response to KA-induced epilepsy. Furthermore, the Weighted gene co-expression network analysis (WGCNA) identified the blue module as being highly associated with epileptic phenotypes. This module consists of genes that exhibit correlated expression patterns specifically related to epilepsy. Within the blue module, 10 genes were further identified as biomarker genes for epilepsy. These genes include MLKL, IRF1, RIPK1, GSDMD, CASP1, CASP8, ZBP1, CASP6, PYCARD, and IL18. These genes likely play critical roles in the pathophysiology of epilepsy and could serve as potential biomarkers for diagnosing or monitoring the condition. Conclusion: In conclusion, our study suggests that the hippocampal neuronal cell death in epilepsy may be closely related to PANoptosis, a novel form of cell death, which provides insights into the underlying pathophysiological processes of epilepsy and helps the development of novel therapeutic approaches for epilepsy.

Variations of the fungal microbiome in Corydalis Rhizoma with different collection areas, processing methods, and storage conditions.

Corydalis Rhizoma (CR, Yanhusuo in Chinese) has been widely used as an analgesic in herbal medicine and functional food. Cases of fungal and mycotoxin contamination in CR have been reported. In this study, the composition and diversity of fungal microbiome in CR samples from four herbal markets and two processing methods were investigated by DNA metabarcoding. Variations of the fungal microbiome in CR during cold and conventional storage were monitored. Results showed that Aspergillus was the dominant genus and saprotroph was the dominant trophic mode. Six potential toxigenic fungi, namely, Aspergillus fumigatus, Aspergillus ostianus, Aspergillus terreus, Penicillium citrinum, Penicillium oxalicum, and Trichothecium roseum, were detected. Differences in fungal composition and diversity among various groups based on collection areas and processing methods were also observed. Moreover, the relative abundance of dominant genera in CR samples stored at different temperatures was significantly different and changed with storage time. This study is the first to reveal the influence of collection areas, processing methods, and storage conditions on the fungal microbiome in CR, which was expected to provide a basis for control strategies of fungal contamination in the industrial chain of CR.

CRISPR-Based Multiplex Detection of Human Papillomaviruses for One-Pot Point-of-Care Diagnostics.

The World Health Organization's global initiative toward eliminating high-risk Human Papillomavirus (hrHPV)-related cancers recommends DNA testing over visual inspection in all settings for primary cancer screening and HPV eradication by 2100. However, multiple hrHPV types cause different types of cancers, and there is a pressing need for an easy-to-use, multiplex point-of-care diagnostic platform for detecting different hrHPV types. Recently, CRISPR-Cas systems have been repurposed for point-of-care detection. Here, we established a CRISPR-Cas multiplexed diagnostic assay (CRISPRD) to detect cervical cancer-causing hrHPVs in one reaction (one-pot assay). We harnessed the compatibility of thermostable AapCas12b, TccCas13a, and HheCas13a nucleases with isothermal amplification and successfully detected HPV16 and HPV18, along with an internal control in a single-pot assay with a limit of detection of 10 copies and 100% specificity. This platform offers a rapid and practical solution for the multiplex detection of hrHPVs, which may facilitate large-scale hrHPV point-of-care screening. Furthermore, the CRISPRD platform programmability enables it to be adapted for the multiplex detection of any two nucleic acid biomarkers as well as internal control.

Modeling denitrification nitrogen losses in China's rice fields based on multiscale field-experiment constraints.

Denitrification plays a critical role in soil nitrogen (N) cycling, affecting N availability in agroecosystems. However, the challenges in direct measurement of denitrification products (NO, N2 O, and N2 ) hinder our understanding of denitrification N losses patterns across the spatial scale. To address this gap, we constructed a data-model fusion method to map the county-scale denitrification N losses from China's rice fields over the past decade. The estimated denitrification N losses as a percentage of N application from 2009 to 2018 were 11.8 ± 4.0% for single rice, 12.4 ± 3.7% for early rice, and 11.6 ± 3.1% for late rice. The model results showed that the spatial heterogeneity of denitrification N losses is primarily driven by edaphic and climatic factors rather than by management practices. In particular, diffusion and production rates emerged as key contributors to the variation of denitrification N losses. These findings humanize a 38.9 ± 4.8 kg N ha-1 N loss by denitrification and challenge the common hypothesis that substrate availability drives the pattern of N losses by denitrification in rice fields.

Functional analysis of a rice 12-oxo-phytodienoic acid reductase gene (OsOPR1) involved in Cd stress tolerance.

BACKGROUND: The accumulation of cadmium (Cd) in plants may compromise the growth and development of plants, thereby endangering human health through the food chain. Understanding how plants respond to Cd is important for breeding low-Cd rice cultivars. METHODS: In this study, the functions of 12-oxo-phytodienoic acid reductase 1 (OsOPR1) were predicted through bioinformatics analysis. The expression levels of OsOPR1 under Cd stress were analyzed by using qRT-PCR. Then, the role that OsOPR1 gene plays in Cd tolerance was studied in Cd-sensitive yeast strain (ycf1), and the Cd concentration of transgenic yeast was analyzed using inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: Bioinformatics analysis revealed that OsOPR1 was a protein with an Old yellow enzyme-like FMN (OYE_like_FMN) domain, and the cis-acting elements which regulate hormone synthesis or responding abiotic stress were abundant in the promoter region, which suggested that OsOPR1 may exhibit multifaceted biological functions. The expression pattern analysis showed that the expression levels of OsOPR1 were induced by Cd stress both in roots and roots of rice plants. However, the induced expression of OsOPR1 by Cd was more significant in the roots compared to that in roots. In addition, the overexpression of OsOPR1 improved the Cd tolerance of yeast cells by affecting the expression of antioxidant enzyme related genes and reducing Cd content in yeast cells. CONCLUSION: Overall, these results suggested that OsOPR1 is a Cd-responsive gene and may has a potential for breeding low-Cd or Cd-tolerant rice cultivars and for phytoremediation of Cd-contaminated in farmland.

Carbon Nanofibers-Based Anodes for Potassium-Ion Battery.

In recent years, with the global warming getting worse and increasing demand for energy, countries around the world are trying to develop new energy storage technologies to solve this problem. Currently, potassium-ion batteries (PIBs) have attracted tremendous attention from researchers as low-cost and high-performance energy storage devices. However, due to the huge ionic radius of K+, PIBs face significant volume expansion during cycling, which can easily lead to the collapse of electrode structures. In addition, the poor diffusion kinetics of K+ seriously affect the electrochemical performance of the battery. Carbon nanofibers (CNFs)-based materials (including CNFs, metal/CNFs composites, chalcogenide/CNFs composites, and other CNFs-based materials) are widely used as PIBs electrode anode materials due to their three-dimensional conductive network, heteroatom doping and excellent mechanical properties. This review discusses in detail the research progress of CNFs-based materials in PIBs, including material preparation, structural design, and performance optimization. On this basis, this article explores the key issues faced by CNFs-based materials and future development directions, and proposes improvement suggestions for providing new ideas for the development of CNFs-based materials.

Achieving Highly Efficient Photocatalytic Hydrogen Evolution through the Construction of g-C3N4@PdS@Pt Nanocomposites.

Selective supported catalysts have emerged as a promising approach to enhance carrier separation, particularly in the realm of photocatalytic hydrogen production. Herein, a pioneering exploration involves the loading of PdS and Pt catalyst onto g-C3N4 nanosheets to construct g-C3N4@PdS@Pt nanocomposites. The photocatalytic activity of nanocomposites was evaluated under visible light and full spectrum irradiation. The results show that g-C3N4@PdS@Pt nanocomposites exhibit excellent properties. Under visible light irradiation, these nanocomposites exhibit a remarkable production rate of 1289 µmol·g-1·h-1, marking a staggering 60-fold increase compared to g-C3N4@Pt (20.9 µmol·g-1·h-1). Furthermore, when subjected to full spectrum irradiation, the hydrogen production efficiency of g-C3N4@PdS@Pt-3 nanocomposites reaches an impressive 11,438 µmol·g-1·h-1, representing an eightfold enhancement compared to g-C3N4@Pt (1452 µmol·g-1·h-1) under identical conditions. Detailed investigations into the microstructure and optical properties of g-C3N4@PdS catalysts were conducted, shedding light on the mechanisms governing photocatalytic hydrogen production. This study offers valuable insights into the potential of these nanocomposites and their pivotal role in advancing photocatalysis.

A portable CRISPR-Cas12a triggered photothermal biosensor for sensitive and visual detection of Staphylococcus aureus and Listeria monocytogenes.

The detection of foodborne pathogens is crucial for ensuring the maintenance of food safety. In the present study, a portable CRISPR-Cas12a triggered photothermal biosensor integrating branch hybrid chain reaction (bHCR) and DNA metallization strategy for sensitive and visual detection of foodborne pathogens was proposed. The sheared probes were utilized to block the locker probes, which enabled preventing the assembly of bHCR in the absence of target bacteria, while target bacteria can activate the cleavage of sheared probes through CRISPR-Cas12a. Therefore, the locker probes functioned as initiating chains, triggering the formation of the branching double-stranded DNA consisting of H1, H2, and H3. The silver particles, which were in situ deposited on the DNA structure, functioned as a signal factor for conducting photothermal detection. Staphylococcus aureus and Listeria monocytogenes were selected as the foodborne pathogens to verify the analytical performance of this CRISPR-Cas12a triggered photothermal sensor platform. The sensor exhibited a sensitive detection with a low detection limit of 1 CFU/mL, while the concentration ranged from 100 to 108 CFU/mL. Furthermore, this method could efficiently detect target bacteria in multiple food samples. The findings demonstrate that this strategy can serve as a valuable reference for the development of a portable platform enabling quantitative analysis, visualization, and highly sensitive detection of foodborne bacteria.

Research progress of microfluidics-based food safety detection.

High demands for food safety detection and analysis have been advocated with people's increasing living standards. Even though numerous analytical testing techniques have been proposed, their widespread adoption is still constrained by the high limit of detection, narrow detection ranges, and high implementation costs. Due to their advantages, such as reduced sample and reagent consumption, high sensitivity, automation, low cost, and portability, using microfluidic devices for food safety monitoring has generated significant interest. This review provides a comprehensive overview of the latest microfluidic detection platforms (published in recent 4 years) and their applications in food safety, aiming to provide references for developing efficient research strategies for food contaminant detection and facilitating the transition of these platforms from laboratory research to practical field use.

Palladium-catalyzed allylation and carbonylation: access to allylhydrazones and allyl acylhydrazones.

A palladium-catalyzed allylation of hydrazines with allyl alcohols and aldehydes was developed, enabling the syntheses of a series of allylhydrazones in good to excellent yields with high regioselectivity. Furthermore, the four-component tandem allylation carbonylation of hydrazines with allyl alcohols and aldehydes was established using the catalytic system, producing various allyl acylhydrazones. Additionally, the functionalized allyl acylhydrazones could be smoothly constructed with the catalytic system employing allylhydrazones as a partner. The catalytic system exhibited good functional tolerance with excellent regioselectivities and scaled-up capability, overcoming the limitations of chemoselectivity of the multicomponent transformation and poor conversion of the weak nucleophile.

Colorectal cancer's burden attributable to a diet high in processed meat in the Belt and Road Initiative countries.

BACKGROUND: Colorectal cancer (CRC) plays a significant role in morbidity, mortality, and economic cost in the Belt and Road Initiative ("B and R") countries. In addition, these countries have a substantial consumption of processed meat. However, the burden and trend of CRC in relation to the consumption of a diet high in processed meat (DHPM-CRC) in these "B and R" countries remain unknown. AIM: To analyze the burden and trend of DHPM-CRC in the "B and R" countries from 1990 to 2019. METHODS: We used the 2019 Global Burden of Disease Study to collate information regarding the burden of DHPM-CRC. Numbers and age-standardized rates (ASRs) of deaths along with the disability-adjusted life years (DALYs) were determined among the "B and R" countries in 1990 and 2019. Using joinpoint regression analysis, the average annual percent change (AAPC) was used to analyze the temporal trends of age-standardized DALYs rate (ASDALR) from 1990 to 2019 and in the final decade (2010-2019). RESULTS: We found geographical differences in the burden of DHPM-CRC among "B and R" countries, with the three highest-ranking countries being the Russian Federation, China, and Ukraine in 1990, and China, the Russian Federation, and Poland in 2019. The burden of DHPM-CRC generally increased in most member countries from 1990 to 2019 (all P < 0.05). The absolute number of deaths and DALYs in DHPM-CRC were 3151.15 [95% uncertainty interval (UI) 665.74-5696.64] and 83249.31 (95%UI 15628.64-151956.31) in China in 2019. However, the number of deaths (2627.57-2528.51) and DALYs (65867.39-55378.65) for DHPM-CRC in the Russian Federation has declined. The fastest increase in ASDALR for DHPM-CRC was observed in Vietnam, Southeast Asia, with an AAPC value of 3.90% [95% confidence interval (CI): 3.63%-4.16%], whereas the fastest decline was observed in Kyrgyzstan, Central Asia, with an AAPC value of -2.05% (95% CI: -2.37% to -1.73%). A substantial upward trend in ASR of mortality, years lived with disability, years of life lost, and DALYs from DHPM-CRC changes in 1990-2019 and the final decade (2010-2019) for most Maritime Silk Route members in East Asia, South Asia, Southeast Asia, North Africa, and the Middle East, as well as Central Europe, while those of the most Land Silk Route members in Central Asia and Eastern Europe have decreased markedly (all P < 0.05). The ASDALR for DHPM-CRC increased more in males than in females (all P < 0.05). For those aged 50-74 years, the ASDALR for DHPM-CRC in 40 members exhibited an increasing trend, except for 20 members, including 7 members in Central Asia, Maldives, and 12 high or high-middle social development index (SDI) members in other regions (all P < 0.05). CONCLUSION: The burden of DHPM-CRC varies substantially across "B and R" countries and threatens public health. Relevant evidence-based policies and interventions tailored to the different trends of countries in SDIs or Silk Routes should be adopted to reduce the future burden of CRC in "B and R" countries via extensive collaboration.

Promoting the proliferation of osteoarthritis chondrocytes by resolvin D1 regulating the NLRP3/caspase-1 signaling pathway.

Osteoarthritis (OA) is a degenerative joint disease commonly found in middle-aged and older people. Chondrocytes are the only cells in joint cartilage that are difficult to heal after pyroptosis, and they will aggravate the wear and tear of joint cartilage and affect the progression of OA. Pyroptosis is a novel form of programmed cell death, and the classical pyroptosis pathway is a programmed cell death pattern mediated by inflammatory cysteine protease-1. Activation of NLRP3 leads to activation and cleavage of caspase-1 precursors, which in turn leads to activation and cleavage of GSDMD proteins and the release of proinflammatory factors. Resolvin D1 (RvD1) is a specialized pro-resolving mediator (SPM) derived from omega-3 unsaturated fatty acids that reduces inflammation and catabolic responses in OA chondrocytes. However, it is unclear whether RvD1 promotes OA chondrocyte proliferation and thus joint cartilage repair. Our results show that RvD1 regulates the NLRP3/caspase-1 signaling pathway by inhibiting the expression of caspase-1, promoting the proliferation of OA chondrocytes, promoting the repair of articular cartilage in rats and delaying the progression of osteoarthritis.