Cardiovascular health and cancer mortality: evidence from US NHANES and UK Biobank cohort studies.

BACKGROUND: The American Heart Association recently introduced a novel cardiovascular health (CVH) metric, Life's Essential 8 (LE8), for health promotion. However, the relationship between LE8 and cancer mortality risk remains uncertain. METHODS: We investigated 17,076 participants from US National Health and Nutrition Examination Survey (US NHANES) and 272,727 participants from UK Biobank, all free of cancer at baseline. The CVH score, based on LE8 metrics, incorporates four health behaviors (diet, physical activity, smoking, and sleep) and four health factors (body mass index, lipid, blood glucose, and blood pressure). Self-reported questionnaires assessed health behaviors. Primary outcomes were mortality rates for total cancer and its subtypes. The association between CVH score (continuous and categorical variable) and outcomes was examined using Cox model with adjustments. Cancer subtypes-related polygenic risk score (PRS) was constructed to evaluate its interactions with CVH on cancer death risk. RESULTS: Over 141,526 person-years in US NHANES, 424 cancer-related deaths occurred, and in UK Biobank, 8,872 cancer deaths were documented during 3,690,893 person-years. High CVH was associated with reduced overall cancer mortality compared to low CVH (HR 0.58, 95% CI 0.37-0.91 in US NHANES; 0.51, 0.46-0.57 in UK Biobank). Each one-standard deviation increase in CVH score was linked to a 19% decrease in cancer mortality (HR: 0.81; 95% CI: 0.73-0.91) in US NHANES and a 19% decrease (HR: 0.81; 95% CI: 0.79-0.83) in UK Biobank. Adhering to ideal CVH was linearly associated with decreased risks of death from lung, bladder, liver, kidney, esophageal, breast, colorectal, pancreatic, and gastric cancers in UK Biobank. Furthermore, integrating genetic data revealed individuals with low PRS and high CVH exhibited the lowest mortality from eight cancers (HRs ranged from 0.36 to 0.57) compared to those with high PRS and low CVH. No significant modification of the association between CVH and mortality risk for eight cancers by genetic predisposition was observed. Subgroup analyses showed a more pronounced protective association for overall cancer mortality among younger participants and those with lower socio-economic status. CONCLUSIONS: Maintaining optimal CVH is associated with a substantial reduction in the risk of overall cancer mortality. Adherence to ideal CVH correlates linearly with decreased mortality risk across multiple cancer subtypes. Individuals with both ideal CVH and high genetic predisposition demonstrated significant health benefits. These findings support adopting ideal CVH as an intervention strategy to mitigate cancer mortality risk and promote healthy aging.

First Report of Klebsiella variicola Causing Tomato Pith Necrosis in Yunnan Province, China.

Tomato (Solanum lycopersicum L.) is a key vegetable crop in China. In August 2023, an outbreak of bacterial pith necrosis in tomato occurred in Lufeng County, Yunnan Province, China, affecting over 40% of the tomato plants in a greenhouse. The stems of infected plants developed a waterlogged soft rot and the disease progressed, the lower leaves and lateral branches of infected plants gradually wilted and died. A longitudinal cut of the stem revealed hollow pith with brown vascular tissue. To isolate the pathogen, the plant surface was disinfested with 75% ethanol. Then, a piece of infected tissue from the base of the stem was excised and immersed in sterile water for 2 min. A small amount of liquid was streaked onto TTC (2,3,5-triphenyltetrazolium chloride) agar medium using an inoculation loop, and plates were incubated at 28℃ for 24 h. Colonies on the TTC plate were white, indicating that the pathogen was not Ralstonia solanacearum. Colonies grown on LB (Luria-Bertani) agar medium were randomly selected and subjected to preliminary pathogenicity tests. Based on the results, a colony named Kv4 was selected and purified through six subcultures in LB agar medium. Biochemical tests showed the strain utilized D-sorbitol, raffinose and citrate but not adonitol, and was positive for methyl red, D-glucose (acid), urea hydrolysis, lysine decarboxylase, and motility, and negative for phenylalanine deaminase, H2S production, indole production, and ornithine decarboxylase. These characteristics align with Klebsiella species (Garrity et al. 2007). To determine the species of strain Kv4, partial sequences of the 16S rDNA, phoE, leuS, and rpoB genes were amplified (Barrios-Camacho et al. 2019) and sequenced. Through BLASTn analysis, strain Kv4 sequences of 16S rDNA (OR888750) had 99.47% identity (1488/1496 bp), phoE (OR899599) had 98.69% (605/613 bp) identity, leuS (OR899598) had 99.07% identity (959/968 bp), and rpoB (OR899597) had 97.69% (633/648 bp) identity with Klebsiella variicola strain FF0907. Using the ClustalW algorithm in MEGA11 for nucleotide sequence alignment, phylogenetic trees were constructed with 16S and phoE, leuS, and rpoB via the neighbor-joining method, confirming strain Kv4 as K. variicola. To test pathogenicity, the roots of 25 'Moneymaker' tomato plants with four to five true leaves were wounded, then each plant inoculated with a 15 mL bacterial suspension (OD600=0.6) of strain Kv4, while the control plants received sterile water. Plants were incubated at 28℃ with a 16 h photoperiod. Experiments were done twice. At 15 days after inoculation (DAI), all plants inoculated with Kv4 showed yellowing, unevenly distributed small black necrotic spots on the leaf surface, and purple-brown soft rot at the stem base. By 18 DAI, there was a gradual transformation of the stem bases from green to purplish brown. At 21 DAI, 60% of the inoculated plants displayed brownish soft rot at the stem base. In contrast, the control plants remained symptom-free. The pathogen was re-isolated from the stem and identified as K. variicola via sequence analysis of 16S, phoE, leuS, and rpoB. In recent years, several new bacterial pith necrosis diseases were reported in tomato (Guo et al. 2023; Ivic et al. 2023). This is the first study documenting K. variicola causing bacterial pith necrosis in tomato. Once considered a benign plant endophyte, Sun et al. (2023) reported K. variicola causing banana sheath rot in Guangdong and Guangxi Provinces, China. Malik et al. (2023) reported that K. variicola caused leaf streak in sorghum in India. This report of bacterial pith necrosis in tomato caused by K. variicola strain Kv4 underscores the escalating threat posed by emerging pathogens to agricultural production. The emergence of K. variicola as a tomato pathogen complicates plant disease management strategies.

FGF21 relieves calcium oxalate-induced cell injury, apoptosis, oxidative damage and ferroptosis of renal tubular epithelial cells through activating Nrf2 signaling pathway.

Nephrolithiasis is a common urological disease accompanied by high morbidity worldwide. Evidences indicate that high-level CaOx crystals in the body can lead to renal tubular epithelial cell (RTEC) injury and RTEC injury is a critical precipitating factor for the formation of kidney stones. FGF21 has recently been revealed as the considerable marker in various kidney dysfunction and exerts the nephroprotective effects in various kidney diseases. This current study was formulated to fully elucidate the biological role of FGF21 in nephrolithiasis and probe into the intrinsic mechanisms underlying the protective effects of FGF21 against RTEC injury. In this work, HK-2 cells were incubated with 100 mg/ml COM for 24 h to establish in vitro RTEC injury model. COM-treated HK-2 cells were transfected with Oe-FGF21 to perform gain-of-function experiments. For rescue experiments, HK-2 cells were pretreated with 10 µM Nrf2 inhibitor ML385 for 24 h to thoroughly discuss the role of Nrf2 signaling in FGF21-mediating nephroprotective effects. It was verified that overexpression of FGF21 relieved COM-induced proliferation inhibition, cell injury, apoptosis, oxidative damage and ferroptosis of RTECs. ML385 treatment partially abolished the protective effects of FGF21 against COM injury in RTECs. In conclusion, up-regulation of FGF21 can relieve COM-induced proliferation inhibition, cell injury, apoptosis, oxidative damage and ferroptosis of RTECs through activating Nrf2 signaling pathway.

Recent advances in genetic engineering to enhance plant-polysaccharide-degrading enzyme expression in Penicillium oxalicum: A brief review.

With the depletion of non-renewable fossil fuels, there has been an increasing emphasis on renewable biomass. Penicillium oxalicum is notable for its exceptional capacity to secrete a diverse array of enzymes that degrade plant polysaccharides into monosaccharides. These valuable monosaccharides can be harnessed in the production of bioethanol and other sustainable forms of energy. By enhancing the production of plant-polysaccharide-degrading enzymes (PPDEs) in P. oxalicum, we can optimize the utilization of plant biomass. This paper presents recent advances in augmenting PPDE expression in P. oxalicum through genetic engineering strategies involving protoplast preparation, transformation, and factors influencing PPDE gene expression.

Proteomic Stratification of Prognosis and Treatment Options for Small Cell Lung Cancer.

Small cell lung cancer (SCLC) is a highly malignant and heterogeneous cancer with limited therapeutic options and prognosis prediction models. Here, we analyzed formalin-fixed, paraffin-embedded (FFPE) samples of surgical resections by proteomic profiling, and stratified SCLC into three proteomic subtypes (S-I, S-II, and S-III) with distinct clinical outcomes and chemotherapy responses. The proteomic subtyping was an independent prognostic factor and performed better than current tumor-node-metastasis or Veterans Administration Lung Study Group staging methods. The subtyping results could be further validated using FFPE biopsy samples from an independent cohort, extending the analysis to both surgical and biopsy samples. The signatures of the S-II subtype in particular suggested potential benefits from immunotherapy. Differentially overexpressed proteins in S-III, the worst prognostic subtype, allowed us to nominate potential therapeutic targets, indicating that patient selection may bring new hope for previously failed clinical trials. Finally, analysis of an independent cohort of SCLC patients who had received immunotherapy validated the prediction that the S-II patients had better progression-free survival and overall survival after first-line immunotherapy. Collectively, our study provides the rationale for future clinical investigations to validate the current findings for more accurate prognosis prediction and precise treatments.

Associations between leisure-time physical activity and the prevalence and incidence of osteoporosis disease: Cross-sectional and prospective findings from the UK biobank.

BACKGROUND: Previous studies underscore the protective role of physical activity (PA) in bone health, yet the relationship between different PA categories and osteoporosis risk remains less explored. Understanding the relationships helps tailor health recommendations and policies to maximize the effects of preventing osteoporosis. METHODS: The cross-sectional study involves 488,403 UK Biobank participants with heel quantitative ultrasound-estimated bone mineral density (eBMD) data. The longitudinal cohort involves 471,394 UK Biobank participants without initial osteoporosis and with follow-up records. PA exposure categories in our study included sedentary behavior (SB), total PA (TPA), and different category-specific PA including household, leisure, and work PA. The cases of osteoporosis were assessed using the International Classification of Diseases, 10th revision (ICD-10). The linear, logistic, and Cox proportional hazard regression models were used in our study. RESULTS: In the cross-sectional study, 15,818 (3.28 %) participants had osteoporosis. TPA levels have a positive correlation with eBMD and a negative correlation with osteoporosis prevalence. Among different categories of PA, higher levels of leisure PA were correlated with increased eBMD and a lower osteoporosis risk (leisure PA: OR: 0.83, 95 % CI: 0.79 to 0.86;). In the longitudinal study, 16,058 (17.6 % male, 82.4 % female) (3.41 %) individuals developed osteoporosis during an average follow-up of 13 years. We observed consistent protective effects of high levels of PA on osteoporosis incidence risk, particularly within the category of leisure PA (TPA: HR: 0.78, 95 % CI: 0.74 to 0.82; leisure PA:HR: 0.83, 95 % CI: 0.80 to 0.87). Such associations are independent of genetic predisposition, with no evidence of gene-PA interactions, and keep steady among individuals using drugs affecting bone-density. Moreover, among different leisure PA items, strenuous sports, other exercises, and walking for pleasure conferred a substantial protective effect against osteoporosis. Additionally, non-elderly individuals and males exhibited lower osteoporosis risk from PA. CONCLUSION: This study highlights activity categories differently associated with the risk of osteoporosis. Adherence to frequent leisure PA may have a protective effect against osteoporosis. Such associations are independent of genetic susceptibility to osteoporosis and keep steady among individuals using drugs affecting bone-density. This highlights that leisure PA could be suggested as a more effective intervention in the primary prevention of osteoporosis.

Neurotrophic keratitis caused by lightning injury: a case report.

BACKGROUND: This study aimed to report a case of neurotrophic keratitis caused by lightning. CASE PRESENTATION: A 38-year-old man was hit by lightning and suffered eye injury. He eventually developed neurotrophic keratitis. RESULTS: The patient's injury history and burn site were analyzed, and it was judged that lightning directly damaged his cornea, eventually resulting in neurotrophic keratitis. Fortunately, the patient's vision improved after treatment. CONCLUSION: Lightning can cause eye damage, and the clinical manifestations are diverse. Lightning currents cause corneal nerve loss, resulting in neurotrophic keratitis. To maintain corneal integrity and prevent disease progression, early assessment and appropriate treatment are necessary.

A multicenter, randomized, open-label, phase 2 clinical study of telitacicept in adult patients with generalized myasthenia gravis.

BACKGROUND AND PURPOSE: This study aimed to investigate the clinical efficacy and safety of telitacicept in patients with generalized myasthenia gravis (gMG) who tested positive for acetylcholine receptor antibodies or muscle-specific kinase antibodies and were receiving standard-of-care therapy. METHODS: Patients meeting the eligibility criteria were randomly assigned to receive telitacicept subcutaneously once a week for 24 weeks in addition to standard-of-care treatment. The primary efficacy endpoint was the mean change in the quantitative myasthenia gravis (QMG) score from baseline to week 24. Secondary efficacy endpoints included mean change in QMG score from baseline to week 12 and gMG clinical absolute score from baseline to week 24. Additionally, safety, tolerability and pharmacodynamics were assessed. RESULTS: Twenty-nine of the 41 patients screened were randomly selected and enrolled. The mean (± standard deviation [SD]) reduction in QMG score from baseline to week 24 was 7.7 (± 5.34) and 9.6 (± 4.29) in the 160 mg and 240 mg groups, respectively. At week 12, mean reductions in QMG scores for these two groups were 5.8 (± 5.85) and 9.5 (± 5.03), respectively, indicating rapid clinical improvement. Safety analysis revealed no adverse events leading to discontinuation or mortalities. All patients showed consistent reductions in serum immunoglobulin (Ig) A, IgG and IgM levels throughout the study. CONCLUSION: Telitacicept demonstrated safety, good tolerability and reduced clinical severity throughout the study period. Further validation of the clinical efficacy of telitacicept in gMG will be conducted in an upcoming phase 3 clinical trial.

Microwave-Solvothermal Synthesis of Mesoporous CeO2/CNCs Nanocomposite for Enhanced Room Temperature NO2 Detection.

Nitrogen dioxide (NO2) gas sensors are pivotal in upholding environmental integrity and human health, necessitating heightened sensitivity and exceptional selectivity. Despite the prevalent use of metal oxide semiconductors (MOSs) for NO2 detection, extant solutions exhibit shortcomings in meeting practical application criteria, specifically in response, selectivity, and operational temperatures. Here, we successfully employed a facile microwave-solvothermal method to synthesize a mesoporous CeO2/CNCs nanocomposite. This methodology entails the rapid and comprehensive dispersion of CeO2 nanoparticles onto helical carbon nanocoils (CNCs), resulting in augmented electronic conductivity and an abundance of active sites within the composite. Consequently, the gas-sensing sensitivity of the nanocomposite at room temperature experienced a notable enhancement. Moreover, the presence of cerium oxide and the conversion of Ce3+ and Ce4+ ions facilitated the generation of oxygen vacancies in the composites, thereby further amplifying the sensing performance. Experimental outcomes demonstrate that the nanocomposite exhibited an approximate 9-fold increase in response to 50 ppm NO2 in comparison to pure CNCs at room temperature. Additionally, the CeO2/CNCs sensor displayed remarkable selectivity towards NO2 when exposed to gases such as NH3, CO, SO2, CO2, and C2H5OH. This straightforward microwave-solvothermal method presents an appealing strategy for the research and development of intelligent sensors based on CNCs nanomaterials.

A circular single-stranded DNA mycovirus infects plants and confers broad-spectrum fungal resistance.

Circular single-stranded DNA (ssDNA) viruses have been rarely found in fungi, and the evolutionary and ecological relationships among ssDNA viruses infecting fungi and other organisms remain unclear. In this study, a novel circular ssDNA virus, tentatively named Diaporthe sojae circular DNA virus 1 (DsCDV1), was identified in the phytopathogenic fungus Diaporthe sojae isolated from pear trees. DsCDV1 has a monopartite genome (3185 nt in size) encapsidated in isometric virions (21-26 nm in diameter). The genome comprises seven putative open reading frames encoding a discrete replicase (Rep) split by an intergenic region, a putative capsid protein (CP), several proteins of unknown function (P1-P4), and a long intergenic region. Notably, the two split parts of DsCDV1 Rep share high identities with the Reps of Geminiviridae and Genomoviridae, respectively, indicating an evolutionary linkage with both families. Phylogenetic analysis based on Rep or CP sequences placed DsCDV1 in a unique cluster, supporting the establishment of a new family, tentatively named Gegemycoviridae, intermediate to both families. DsCDV1 significantly attenuates fungal growth and nearly erases fungal virulence when transfected into the host fungus. Remarkably, DsCDV1 can systematically infect tobacco and pear seedlings, providing broad-spectrum resistance to fungal diseases. Subcellular localization analysis revealed that DsCDV1 P3 is systematically localized in the plasmodesmata, while its expression in trans-complementation experiments could restore systematic infection of a movement-deficient plant virus, suggesting that P3 is a movement protein. DsCDV1 exhibits unique molecular and biological traits not observed in other ssDNA viruses, serving as a link between fungal and plant ssDNA viruses and presenting an evolutionary connection between ssDNA viruses and fungi. These findings contribute to expanding our understanding of ssDNA virus diversity and evolution, offering potential biocontrol applications for managing crucial plant diseases.

Elabela ameliorates neuronal pyroptosis and mitochondrial fission via APJ/ZBP1 signaling in ischemic stroke.

Pyroptosis signifies a significant form of programmed neuronal demise subsequent to ischemic stroke. In our prior investigations, we demonstrated that the Elabela (ELA)-Apelin receptor (APJ) axis alleviated neuronal death by improving collateral circulation and mitigating ferroptosis in a murine model of middle cerebral artery occlusion (MCAO). However, the connection between ELA and neuronal pyroptosis remains further elucidation. Here, we observed an upregulation of ELA and APJ expression in both murine brain specimens and cultured HT-22 hippocampal neurons exposed to experimental ischemic stroke. ELA administration markedly diminished the infarct size in comparison to controls. ELA treatment ameliorated neurological deficits and anxiety-like symptoms in mice with stroke, concurrently inhibiting pyroptosis and mitochondria fission in neurons. Conversely, ELA knockdown yielded the opposite effects. Utilizing RNA-sequencing analysis, we identified a candidate for pyroptosis priming, Z-DNA-binding protein 1 (ZBP1), which was suppressed in ELA-treated HT-22 neurons during oxygen-glucose deprivation/reperfusion (OGD/R). Subsequent co-immunoprecipitation analyses demonstrated the binding between APJ and ZBP1. Specifically, APJ suppressed ZBP1 to inhibit NLRP3 inflammasome activation and dynamin-related protein 1-mediated mitochondrial fission in neurons. In summary, our findings suggest that ELA functions as a stroke-induced signal limiting neuronal pyroptosis and mitochondrial fission via APJ/ZBP1 signaling, thereby underscoring ELA as a potential therapeutic target for ischemic stroke treatment.

A meta-analysis of risk factors for a Dacron-cuffed catheter related infection in hemodialysis.

OBJECTIVE: To provide theoretical basis for prevention of a Dacron-cuffed catheter related infection (CRI), the risk factors of CRI in hemodialysis patients were systematically evaluated. METHODS: Eight databases, including PubMed, Cochrane library, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Database (CBM), Wanfang Database and Chinese Scientific Journal Database (VIP), were searched to screen out literatures related to the risk factors of long-term indwelling a Dacron-cuffed CRI in hemodialysis. Meta-analysis of risk factors for a Dacron-cuffed CRI in hemodialysis and publication bias test were performed using RevMan 5.4 software. RESULTS: After screening, 13 literatures involving a Dacron-cuffed CRI were included, with a total of 625 patients, and the infection rate was 11.7%. The combined OR value and 95% confidence interval (CI) of all factors were: Combined with Diabetes (1.94, 1.51 ~ 2.50), Hb (1.82, 1.35 ~ 2.44), age (2.38, 1.06 ~ 5.34), catheter indwelling time (1.79, 1.21 ~ 2.66), serum albumin (2.26, 1.25 ~ 4.08), catheter indwelling site (3.29, 1.74 ~ 6.23) and the number of tube placement (5.40, 2.65 ~ 11.02). CONCLUSIONS: The main risk factors for a Dacron-cuffed CRI in hemodialysis were combined with diabetes, hemoglobin level, age, catheter indwelling time, serum albumin level, femoral vein catheter indwelling and catheterization times. In other words, hemodialysis patients are at higher risk of CRI if they have diabetes, or if they have a lower hemoglobin level, or if they are older, or if they have a longer duration of catheterization, or if they have a lower serum albumin level, or if they have a femoral vein catheter, or if they have more catheters.

Triple-negative accessory breast cancer occurring concurrently with primary invasive breast carcinoma: a case report.

Introduction: Accessory breast cancer (ABC) is an extremely rare condition, particularly the presence of triple-negative ABC with ipsilateral invasive in situ breast cancer. Binary breast tumors are controversial in terms of surgical methods and comprehensive treatment. Case presentation: We share the case of a 64-year-old postmenopausal woman who presented with an underarm mass for 3 months. Ultrasonography and computed tomography suggested possible breast cancer with axillary lymph node metastasis. The patient underwent a left modified radical mastectomy combined with axillary lymph node dissection. The postoperative pathology confirmed a binary tumor, prompting us to initiate comprehensive treatment. Conclusion: We present the treatment approach for a rare case of triple-negative para-breast cancer complicated with carcinoma in situ of the breast, hoping to contribute new therapeutic ideas for the treatment of this disease.

Natural Allelic Variations of Bch10G006400 Controlling Seed Size in Chieh-qua (Benincasa hispida Cogn. var. Chieh-qua How).

Seeds are the most important reproductive organs of higher plants, the beginning and end of a plant's lifecycle. They are very important to plant growth and development, and also an important factor affecting yield. In this study, genetic analysis and BSA-seq of the F2 population crossed with the large-seeded material 'J16' and small-seeded material 'FJ5' were carried out, and the seed size locus was initially located within the 1.31 Mb region on chr10. In addition, 2281 F2 plants were used to further reduce the candidate interval to 48.8 Kb. This region contains only one gene encoding the N-acetyltransferase (NAT) protein (Bch10G006400). Transcriptome and expression analysis revealed that the gene was significantly more highly expressed in 'J16' than in 'FJ5'. Variation analysis of Bch10G006400 among parents and 50 chieh-qua germplasms revealed that as well as a nonsynonymous mutation (SNP_314) between parents, two mutations (SNP_400 and InDel_551) were detected in other materials. Combining these three mutations completely distinguished the seed size of the chieh-qua. GO and KEGG enrichment analyses revealed that DGEs played the most important roles in carbohydrate metabolism and plant hormone signal transduction, respectively. The results of this study provide important information for molecular marker-assisted breeding and help to reveal the molecular mechanism of seed size.

Trend analysis and prediction of the incidence and mortality of CKD in China and the US.

BACKGROUND: Currently, limited research is available on the comparative analysis of chronic kidney disease (CKD) incidence and mortality rates between China and the United States. This study aimed to explore the trends in CKD incidence and mortality rates in both countries, as well as make some future predictions. METHODS: The data on CKD incidence and mortality in China and the US from 1990 to 2019 were derived from the 2019 Global Burden of Disease database. A Joinpoint regression model was used to analyze temporal trends in CKD incidence and mortality. An age-period-cohort model was used to assess the effects of age, period, and birth cohort on CKD risk and forecast the age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) of CKD in China and the US over the next 15 years. RESULTS: CKD incidence in China and the US showed an upward trend. Its mortality rate showed a downward trend in China but an upward one in the US. The relative risk (RR) of CKD incidence and mortality increases with age. The RR of CKD incidence in the 0-5 age group exceeds that in the 5-55 age group, and the RR for mortality surpasses that in the 5-35 age group. Over time, the RR of CKD incidence has gradually increased in China and the US. Individuals born in later birth cohorts had a lower RR of CKD incidence and mortality. The ASIR of CKD may increase in both China and the US, whereas its ASMR may decline over the next 15 years. CONCLUSION: Screening measures should be strengthened among populations at high risk of CKD; prenatal examinations of pregnant women should be emphasized to reduce CKD incidence in newborns. It is imperative to increase health education and encourage individuals to adopt healthy lifestyles.

Exploring the impact of high-altitude de-acclimatization on renal function: The roles of oxidative and endoplasmic reticulum stress in rat models.

BACKGROUND: High-altitude de-acclimatization (HADA) significantly impacts physiological functions when individuals acclimatize to high altitudes return to lower altitudes. This study investigates HADA's effects on renal function and structure in rats, focusing on oxidative and endoplasmic reticulum stress as potential mechanisms of renal injury. OBJECTIVE: To elucidate the pathophysiological mechanisms of renal damage in HADA and evaluate the efficacy of antioxidants Vitamin C (Vit C) and tauroursodeoxycholic acid (TUDCA) in mitigating these effects. METHODS: 88 male Sprague-Dawley rats were randomly divided into a control group, a high-altitude (HA) group, a high-altitude de-acclimatization (HADA) group, and a treatment group. The control group was housed in a sea level environment (500 m), while the HA, HADA, and treatment groups were placed in a simulated high-altitude chamber (5000 m) for 90 days. After this period, the HA group completed the modeling phase; the HADA group was further subdivided into four subgroups, each continuing to be housed in a sea level environment for 3, 7, 14, and 30 days, respectively. The treatment group was split into the Vit C group, the TUDCA group, and two placebo groups, receiving medication for 3 consecutive days, once daily upon return to the sea level. The Vit C group received 100 mg/kg Vit C solution via intravenous injection, the TUDCA group received 250 mg/kg TUDCA solution via intraperitoneal injection, and the placebo groups received an equivalent volume of saline similarly. Serum, urine, and kidney tissues were collected immediately after the modeling phase. Renal function and oxidative stress levels were assessed using biochemical and ELISA methods. Renal histopathology was observed with H&E, Masson's trichrome, PAS, and PASM staining. Transmission electron microscopy was used to examine the ultrastructure of glomeruli and filtration barrier. TUNEL staining assessed cortical apoptosis in the kidneys. Metabolomics was employed for differential metabolite screening and pathway enrichment analysis. RESULTS: Compared to the control and HA groups, the HADA 3-day group (HADA-3D) exhibited elevated renal function indicators, significant pathological damage, observable ultrastructural alterations including endoplasmic reticulum expansion and apoptosis. TUNEL-positive cells significantly increased, indicating heightened oxidative stress levels. Various differential metabolites were enriched in pathways related to oxidative and endoplasmic reticulum stress. Early intervention with Vit C and TUDCA markedly alleviated renal injury in HADA rats, significantly reducing the number of apoptotic cells, mitigating endoplasmic reticulum stress, and substantially lowering oxidative stress levels. CONCLUSION: This study elucidates the pivotal roles of oxidative and endoplasmic reticulum stress in the early-stage renal injury in rats undergoing HADA. Early intervention with the Vit C and TUDCA significantly mitigates renal damage caused by HADA. These findings provide insights into the pathophysiological mechanisms of HADA and suggest potential therapeutic strategies for its future management.

The immune cell infiltration-associated molecular subtypes and gene signature predict prognosis for osteosarcoma patients.

Host immune dysregulation involves in the initiation and development of osteosarcoma (OS). However, the exact role of immune cells in OS remains unknown. We aimed to distinguish the molecular subtypes and establish a prognostic model in OS patients based on immunocyte infiltration. The gene expression profile and corresponding clinical feature of OS patients were obtained from TARGET and GSE21257 datasets. MCP-counter and univariate Cox regression analyses were applied to identify immune cell infiltration-related molecular subgroups. Functional enrichment analysis and immunocyte infiltration analysis were performed between two subgroups. Furthermore, Cox regression and LASSO analyses were performed to establish the prognostic model for the prediction of prognosis and metastasis in OS patients. The subgroup with low infiltration of monocytic lineage (ML) was related to bad prognosis in OS patients. 435 DEGs were screened between the two subgroups. Functional enrichment analysis revealed these DEGs were involved in immune- and inflammation-related pathways. Three important genes (including TERT, CCDC26, and IL2RA) were identified to establish the prognostic model. The risk model had good prognostic performance for the prediction of metastasis and overall survival in OS patients. A novel stratification system was established based on ML-related signature. The risk model could predict the metastasis and prognosis in OS patients. Our findings offered a novel sight for the prognosis and development of OS.

Modulating root system architecture: cross-talk between auxin and phytohormones.

Root architecture is an important agronomic trait that plays an essential role in water uptake, soil compactions, nutrient recycling, plant-microbe interactions, and hormone-mediated signaling pathways. Recently, significant advancements have been made in understanding how the complex interactions of phytohormones regulate the dynamic organization of root architecture in crops. Moreover, phytohormones, particularly auxin, act as internal regulators of root development in soil, starting from the early organogenesis to the formation of root hair (RH) through diverse signaling mechanisms. However, a considerable gap remains in understanding the hormonal cross-talk during various developmental stages of roots. This review examines the dynamic aspects of phytohormone signaling, cross-talk mechanisms, and the activation of transcription factors (TFs) throughout various developmental stages of the root life cycle. Understanding these developmental processes, together with hormonal signaling and molecular engineering in crops, can improve our knowledge of root development under various environmental conditions.

Mage transposon: a novel gene delivery system for mammalian cells.

Transposons, as non-viral integration vectors, provide a secure and efficient method for stable gene delivery. In this study, we have discovered Mage (MG), a novel member of the piggyBac(PB) family, which exhibits strong transposability in a variety of mammalian cells and primary T cells. The wild-type MG showed a weaker insertion preference for near genes, transcription start sites (TSS), CpG islands, and DNaseI hypersensitive sites in comparison to PB, approaching the random insertion pattern. Utilizing in silico virtual screening and feasible combinatorial mutagenesis in vitro, we effectively produced the hyperactive MG transposase (hyMagease). This variant boasts a transposition rate 60% greater than its native counterpart without significantly altering its insertion pattern. Furthermore, we applied the hyMagease to efficiently deliver chimeric antigen receptor (CAR) into T cells, leading to stable high-level expression and inducing significant anti-tumor effects both in vitro and in xenograft mice models. These findings provide a compelling tool for gene transfer research, emphasizing its potential and prospects in the domains of genetic engineering and gene therapy.