Application of a virtual ruler (VR) in predicting postoperative rebleeding from esophageal varices in patients with liver cirrhosis.

BACKGROUND: Esophageal variceal diameter (EVD) is one of the most important predictors of variceal bleeding, as well as an important predictor of the effectiveness of endoscopic esophageal varices (EV) treatments. EVD is currently determined using visual inspection by endoscopic operators, meaning that results can vary widely between operators. This approach also means that cases unsuitable for Endoscopic variceal ligation(EVL) can be complicated by postoperative hemorrhage. Thus, the purpose of this study was to explore the value of a virtual ruler (VR) in predicting rebleeding after the endoscopic treatment of EV in patients with cirrhosis. METHODS: We enrolled 588 patients with cirrhosis and EV (with and without gastric varices), who were treated with EVL or Endoscopic injection sclerotherapy (EIS) across three hospitals. We categorized participants into a non-bleeding group and a rebleeding group according to whether they bled again after surgery. We compared basic demographic and clinical data, laboratory tests, EVD, and treatment modalities between the two groups. Potential risk factors for rebleeding after EV operations were analyzed using univariate and multivariable regression analyses. Correlations between esophageal variceal rebleeding and EVD were also analyzed, as was consistency between visual EVD estimates and EVD measured using a VR. RESULTS: Child-Pugh class, Albumin (ALB)levels, Prothrombin Time (PT) levels, EVD (Visual value), EVD(VR value), red sign, and the number of laps used for EVL showed statistically significant differences between the rebleeding and non-bleeding groups. Univariate regression analysis showed that Child-Pugh classification, ALB levels, PT levels, EVD( VR value), and red sign were strongly associated with rebleeding after endoscopic treatment of EV, while multivariable regression analysis showed that Child-Pugh classification, ALB levels, and EVD (VR value) were predictive factors for rebleeding after endoscopic treatment of EV. Differences between visual EVD estimates and VR EVD measurements were large. (Kappa value: 0.391, p < 0.001). However, the two methods showed high agreement for EVD > 1cm (87/95) CONCLUSIONS: EVD (VR value) can more accurately predict rebleeding rates. It can also provide a basis for selecting appropriate endoscopic treatment modalities for EV and effectively circumvent postoperative EV rebleeding.

Higher-Form Symmetries under Weak Measurement.

We aim to address the following question: if we start with a quantum state with a spontaneously broken higher-form symmetry, what is the fate of the system under weak local quantum measurements? We demonstrate that under certain conditions, a phase transition can be driven by weak measurements, which suppresses the spontaneous breaking of the 1-form symmetry and weakens the 1-form symmetry charge fluctuation. We analyze the nature of the transitions employing the tool of duality, and we demonstrate that some of the transitions driven by weak measurement enjoy a line of fixed points with self-duality.

The TaGW2-TaSPL14 module regulates the trade-off between tiller number and grain weight in wheat.

IDEAL PLANT ARCHITECTURE1 (IPA1) is a pivotal gene controlling plant architecture and grain yield. However, little is known about the effects of Triticum aestivum SQUAMOSA PROMOTER-BINDING-LIKE 14 (TaSPL14), an IPA1 ortholog in wheat, on balancing yield traits and its regulatory mechanism in wheat (T. aestivum L.). Here, we determined that the T. aestivum GRAIN WIDTH2 (TaGW2)-TaSPL14 module influences the balance between tiller number and grain weight in wheat. Overexpression of TaSPL14 resulted in a reduced tiller number and increased grain weight, whereas its knockout had the opposite effect, indicating that TaSPL14 negatively regulates tillering while positively regulating grain weight. We further identified TaGW2 as a novel interacting protein of TaSPL14 and confirmed its ability to mediate the ubiquitination and degradation of TaSPL14. Based on our genetic evidence, TaGW2 acts as a positive regulator of tiller number, in addition to its known role as a negative regulator of grain weight, which is opposite to TaSPL14. Moreover, combinations of TaSPL14-7A and TaGW2-6A haplotypes exhibit significantly additive effects on tiller number and grain weight in wheat breeding. Our findings provide insight into how the TaGW2-TaSPL14 module regulates the trade-off between tiller number and grain weight and its potential application in improving wheat yield.

Treatment of manganese and lead poisoning with sodium para-aminosalicylic acid: A contemporary update.

Sodium para-aminosalicylic acid (PAS-Na) treatment for manganese (Mn) intoxication has shown efficacy in experimental and clinical studies, giving rise to additional studies on its efficacy for lead (Pb) neurotoxicity and its associated mechanisms of neuroprotection. The difference between PAS-Na and other metal complexing agents, such as edetate calcium sodium (CaNa2-EDTA), is firstly that PAS-Na can readily pass through the blood-brain barrier (BBB), and complex and facilitate the excretion of manganese and lead. Secondly, PAS-Na has anti-inflammatory effects. Recent studies have broadened the understanding on the mechanisms associated with efficacy of PAS-Na. The latter has been shown to modulate multifarious manganese- and lead- induced neurotoxicity, via its anti-apoptotic and anti-inflammatory effects, as well as its ability to inhibit pyroptosis, and regulate abnormal autophagic processes. These observations provide novel scientific bases and new concepts for the treatment of lead, mercury, copper, thallium, as well as other toxic encephalopathies, and implicate PAS-Na as a compound with greater prospects for clinical medical application.

The impact of CYP3A4 genetic polymorphism on crizotinib metabolism and drug-drug interactions.

To elucidate the impact of CYP3A4 activity inhibition and genetic polymorphism on the metabolism of crizotinib. Enzymatic incubation systems for crizotinib were established, and Sprague-Dawley rats were utilized for in vivo experiments. Analytes were quantified using LC-MS/MS. Upon screening 122 drugs and natural compounds, proanthocyanidins emerged as inhibitor of crizotinib metabolism, exhibiting a relative inhibition rate of 93.7%. The IC50 values were 24.53 ± 0.32 µM in rat liver microsomes and 18.24 ± 0.12 µM in human liver microsomes. In vivo studies revealed that proanthocyanidins markedly affected the pharmacokinetic parameters of crizotinib. Co-administration led to a significant reduction in the AUC(0-t), Cmax of PF-06260182 (the primary metabolite of crizotinib), and the urinary metabolic ratio. This interaction is attributed to the mixed-type inhibition of liver microsome activity by proanthocyanidins. CYP3A4, being the principal metabolic enzyme for crizotinib, has its genetic polymorphisms significantly influencing crizotinib's pharmacokinetics. Kinetic data showed that the relative metabolic rates of crizotinib across 26 CYP3A4 variants ranged from 13.14% (CYP3A4.12, 13) to 188.57% (CYP3A4.33) when compared to the wild-type CYP3A4.1. Additionally, the inhibitory effects of proanthocyanidins varied between CYP3A4.12 and CYP3A4.33, when compared to the wild type. Our findings indicate that proanthocyanidins coadministration and CYP3A4 genetic polymorphism can significantly influence crizotinib metabolism.

Ability of Helicobacter pylori to internalize into Candida.

The following are our views regarding the "letter to the editor" (Helicobacter is preserved in yeast vacuoles! Does Koch's postulates confirm it?) by Alipour and Gaeini, and the response "letter to the editor" (Candida accommodates non-culturable Helicobacter pylori in its vacuole-Koch's postulates aren't applicable) by Siavoshi and Saniee. Alipour and Gaeini rejected the methods, results, discussion, and conclusions summarized in a review article by Siavoshi and Saniee. The present article reviews and discusses evidence on the evolutionary adaptation of Helicobacter pylori (H. pylori) to thrive in Candida cell vacuoles and concludes that Candida could act as a Trojan horse, transporting potentially infectious H. pylori into the stomach of humans.

Disorder Operator and Rényi Entanglement Entropy of Symmetric Mass Generation.

The "symmetric mass generation" (SMG) quantum phase transition discovered in recent years has attracted great interest from both condensed matter and high energy theory communities. Here, interacting Dirac fermions acquire a gap without condensing any fermion bilinear mass term or any concomitant spontaneous symmetry breaking. It is hence beyond the conventional Gross-Neveu-Yukawa-Higgs paradigm. One important question we address in this Letter is whether the SMG transition corresponds to a true unitary conformal field theory. We employ the sharp diagnosis including the scaling of disorder operator and Rényi entanglement entropy in large-scale lattice model quantum Monte Carlo simulations. Our results strongly suggest that the SMG transition is indeed an unconventional quantum phase transition and it should correspond to a true (2+1)d unitary conformal field theory.

Associations of per- and polyfluoroalkyl substances (PFAS) and their mixture with risk of rheumatoid arthritis in the U.S. adult population.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are known environmental contaminants with immunosuppressive properties. Their connection to rheumatoid arthritis (RA), a condition influenced by the immune system, is not well studied. This research explores the association between PFAS exposure and RA prevalence. METHODS: This research utilized data from the NHANES, encompassing a sample of 10,496 adults from the 2003-2018 cycles, focusing on serum levels of several PFAS. The presence of RA was determined based on self-reports. This study used multivariable logistic regression to assess the relationship between individual PFAS and RA risk, adjusting for covariates to calculate odds ratios (ORs). The combined effects of PFAS mixtures were evaluated using BKMR, WQS regression, and quantile g-computation. Additionally, sex-specific associations were explored through stratified analysis. RESULTS: Higher serum PFOA (OR = 0.88, 95% CI: 0.79, 0.98), PFHxS (OR = 0.91, 95% CI: 0.83, 1.00), PFNA (OR = 0.87, 95% CI: 0.77, 0.98), and PFDA (OR = 0.89, 95% CI: 0.81, 0.99) concentration was related to lower odds of RA. Sex-specific analysis in single chemical models indicated the significant inverse associations were only evident in females. BKMR did not show an obvious pattern of RA estimates across PFAS mixture. The outcomes of sex-stratified quantile g-computation demonstrated that an increase in PFAS mixture was associated with a decreased odds of RA in females (OR: 0.76, 95% CI: 0.62, 0.92). We identified a significant interaction term of the WQS*sex in the 100 repeated hold out WQS analysis. Notably, a higher concentration of the PFAS mixture was significantly associated with reduced odds of RA in females (mean OR = 0.93, 95% CI: 0.88, 0.98). CONCLUSIONS: This study indicates potential sex-specific associations of exposure to various individual PFAS and their mixtures with RA. Notably, the observed inverse relationships were statistically significant in females but not in males. These findings contribute to the growing body of evidence indicating that PFAS may have immunosuppressive effects.

A facile and smart strategy to enhance bone regeneration with efficient vitamin D3 delivery through sterosome technology.

The spontaneous healing of critical-sized bone defects is often limited, posing an increased risk of complications and suboptimal outcomes. Osteogenesis, a complex process central to bone formation, relies significantly on the pivotal role of osteoblasts. Despite the well-established osteogenic properties of vitamin D3 (VD3), its lipophilic nature confines administration to oral or muscle injection routes. Therefore, a strategic therapeutic approach involves designing a multifunctional carrier to enhance efficacy, potentially incorporating it into the delivery system. Here, we introduce an innovative sterosome-based delivery system, utilizing palmitic acid (PA) and VD3, aimed at promoting osteogenic differentiation and facilitating post-defect bone regeneration. The delivery system exhibited robust physical characteristics, including excellent stability, loading efficiency, sustained drug release and high cellular uptake efficiency. Furthermore, comprehensive investigations demonstrated outstanding biocompatibility and osteogenic potential in both 2D and 3D in vitro settings. A critical-sized calvarial defect model in mice recapitulated the notable osteogenic effects of the sterosomes in vivo. Collectively, our research proposes a clinically applicable strategy for bone healing, leveraging PA/VD3 sterosomes as an efficient carrier to deliver VD3 and enhance bone regenerative effects.

Association between ambient particulate matter exposure and mitochondrial DNA copy number: A systematic review and meta-analysis.

BACKGROUND: Ambient particulate matter (PM) has been recognized as inducing oxidative stress, which could contribute to mitochondrial damage and dysfunction. However, studies investigating the association between ambient PM and mitochondria, particularly mitochondrial DNA copy number (mtDNA-CN), have yielded inconsistent results. METHODS: We conducted comprehensive literature searches to identify observational studies published before July 17, 2023, examining the association between ambient PM exposure and mtDNA-CN. Meta-analysis using random effects model was employed to calculate the pooled effect estimates for general individual exposures, as well as for prenatal exposure with specific trimester. Additionally, the quality and level of evidence for each exposure-outcome pair was evaluated. RESULTS: A total of 10 studies were included in the systematic review and meta-analysis. The results indicated that general individual exposure to PM2.5 (ß = -0.084, 95 % CI: -0.521, 0.353; I2 = 93 %) and PM10 (ß = 0.035, 95 % CI: -0.129, 0.199; I2 = 95 %) did not significantly affect mtDNA-CN. Prenatal exposure to PM2.5 (ß = 0.023, 95 % CI: -0.087, 0.133; I2 = 0 %) and PM10 (ß = 0.006, 95 % CI: -0.135; 0.147; I2 = 51 %) were also not significantly associated with mtDNA-CN in offspring. The level of evidence for each tested exposure-outcome pair was assessed as "inadequate." CONCLUSIONS: The findings of this systematic review and meta-analysis indicate that there is an "inadequate" strength of evidence for the association between general individual or prenatal exposure to ambient PM and mtDNA-CN. Future research necessitates studies with more rigorous design, enhanced control of confounding factors, and improved measures of exposure to substantiate our findings.

New entity of adult ultra-short coeliac disease: the first international cohort and case-control study.

BACKGROUND: Ultra-short coeliac disease (USCD) is defined as villous atrophy only present in the duodenal bulb (D1) with concurrent positive coeliac serology. We present the first, multicentre, international study of patients with USCD. METHODS: Patients with USCD were identified from 10 tertiary hospitals (6 from Europe, 2 from Asia, 1 from North America and 1 from Australasia) and compared with age-matched and sex-matched patients with conventional coeliac disease. FINDINGS: Patients with USCD (n=137, median age 27 years, IQR 21-43 years; 73% female) were younger than those with conventional coeliac disease (27 vs 38 years, respectively, p<0.001). Immunoglobulin A-tissue transglutaminase (IgA-tTG) titres at index gastroscopy were lower in patients with USCD versus conventional coeliac disease (1.8×upper limit of normal (ULN) (IQR 1.1-5.9) vs 12.6×ULN (IQR 3.3-18.3), p<0.001).Patients with USCD had the same number of symptoms overall (median 3 (IQR 2-4) vs 3 (IQR 1-4), p=0.875). Patients with USCD experienced less iron deficiency (41.8% vs 22.4%, p=0.006).Both USCD and conventional coeliac disease had the same intraepithelial lymphocytes immunophenotype staining pattern; positive for CD3 and CD8, but not CD4.At follow-up having commenced a gluten-free diet (GFD) (median of 1181 days IQR: 440-2160 days) both USCD and the age-matched and sex-matched controls experienced a similar reduction in IgA-tTG titres (0.5 ULN (IQR 0.2-1.4) vs 0.7 ULN (IQR 0.2-2.6), p=0.312). 95.7% of patients with USCD reported a clinical improvement in their symptoms. INTERPRETATION: Patients with USCD are younger, have a similar symptomatic burden and benefit from a GFD. This study endorses the recommendation of D1 sampling as part of the endoscopic coeliac disease diagnostic workup.

Exposure to pesticides and risk of colorectal cancer: A systematic review and meta-analysis.

Colorectal cancer (CRC) is a widespread malignancy worldwide, and its relationship with pesticide exposure remains inconclusive. This study aims to elucidate the relationship between pesticide exposure and the risk of colon, rectal, or CRC, focusing on specific pesticide groups. We conducted an extensive literature search for peer-reviewed studies published up to March 31, 2023. Summary risk ratios (RR) and their corresponding 95% confidence intervals (CI) were calculated using stratified random-effects meta-analyses, taking into account different types of exposure and outcomes, and various exposed populations and pesticide subgroups. This approach aimed to address the substantial heterogeneity observed across the literature. We also assessed heterogeneity and potential small-study effects to ensure the robustness of our findings. From the 50 studies included in this review, 33 contributed to the meta-analysis. Our results indicate a significant association between herbicide exposure and colon cancer in both lifetime-days (LDs) (RR = 1.20; 95% CI = 1.01-1.42) and intensity-weighted lifetime-days (IWLDs) (RR = 1.29, 95% CI = 1.12-1.49) exposure. Similarly, insecticide exposure was associated with an increased risk of colon cancer in IWLDs (RR = 1.32; 95% CI = 1.02-1.70) exposure, and rectal cancer in any versus never exposure (RR = 1.21; 95% CI = 1.07-1.36), IDs (RR = 1.86; 95% CI = 1.30-2.67) and IWLDs (RR = 1.70; 95% CI = 1.03-2.83) exposure. While these findings suggest significant associations of herbicide and insecticide exposure with colon and rectal cancer, respectively, further research is needed to explore the impact of other pesticide groups and deepen our understanding of pesticide exposure. These results have important implications for policymakers and regulators, underscoring the need for stricter supervision and regulation of pesticide use to mitigate CRC risk.

Comparison between high-flow nasal cannula and conventional oxygen therapy in COVID-19 patients: a systematic review and meta-analysis.

BACKGROUND: High-flow nasal cannula (HFNC) and conventional oxygen therapy (COT) are important respiratory support strategies for acute hypoxemic respiratory failure (AHRF) in coronavirus disease 2019 (COVID-19) patients. However, the results are conflicting for the risk of intubation with HFNC as compared to COT. OBJECTIVES: We systematically synthesized the outcomes of HFNC relative to COT in COVID-19 patients with AHRF and evaluated these outcomes in relevant subpopulations. DESIGN: This study was designed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. DATA SOURCES AND METHODS: We searched PubMed, EMBASE, Web of Science, Scopus, ClinicalTrials.gov, medRxiv, BioRxiv, and the Cochrane Central Register of Controlled Trials for randomized controlled trials and observational studies that compared the efficacy of HFNC with COT in patients with COVID-19-related AHRF. Primary outcomes were intubation rate and mortality rate. Secondary outcomes were the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2), respiratory rate, hospital length of stay, intensive care unit (ICU) length of stay, and days free from invasive mechanical ventilation. RESULTS: In total, 20 studies with 5732 patients were included. We found a decreased risk of requiring intubation in HFNC compared to COT [odds ratio (OR) = 0.61, 95% confidence interval (CI): 0.46-0.82, p = 0.0009, I2 = 75%]. Similarly, we found HFNC was associated with lower risk of intubation rate compared to COT in the subgroup of patients with baseline PaO2/FiO2 < 200 mmHg (OR = 0.69, 95% CI: 0.55-0.86, p = 0.0007, I2 = 45%), and who were in ICU settings at enrollment (OR = 0.57, 95% CI: 0.38-0.85, p = 0.005, I2 = 80%). HFNC was associated with an improvement of PaO2/FiO2 and respiratory rate compared to COT. The use of HFNC compared to COT did not reduce the mortality rate, days free from invasive mechanical ventilation, hospital length of stay, or ICU length of stay. CONCLUSION: Compared to COT, HFNC may decrease the need for tracheal intubation in patients with COVID-19-related AHRF, particularly among patients with baseline PaO2/FiO2 < 200 mmHg and those in ICU settings. TRIAL REGISTRATION: This systematic review and meta-analysis protocol was prospectively registered with PROSPERO (no. CRD42022339072).

A short-term study of laparoscopic-dominant individualised levator ani resection in abdominoperineal resection: A retrospective investigation.

OBJECTIVE: The objective is to investigate if laparoscopic-dominant abdominoperineal resection (LDAPR) with individualised levator ani resection inhibits local recurrence (LR) and prolongs survival as compared to laparoscopic abdominoperineal resection (APR). MATERIALS AND METHODS: Rectal cancer surgery cases were retrospectively identified from September 2014 to December 2019. LDAPR-treated group (55 patients) and the APR-treated group (71 patients) were included in the study. The operation time, circumferential resection margin (CRM), intraoperative tumor surgery (ITP), post-operative complications, the 2-year overall survival (OS) and LR were compared in the two groups. RESULTS: The CRM and ITP were significantly reduced in the LDAPR as compared to the APR group (3.6% vs. 16.9%, t = 5.522, P = 0.019; 3.6% vs. 14.1%, t = 3.926, P = 0.048). In terms of post-operative complications, the incidence of urinary retention in LDAPR was significantly reduced than the APR group (10.9% vs. 25.4%, χ2 = 4.139, P = 0.041). Similarly, perineal pain at 6 months or 1 year after surgery was significantly down-regulated in LDAPR than in the APR group (72.7% vs. 88.7%, χ2 = 5.320, P = 0.021; 18.2% vs. 43.2%, χ2 = 8.288, P = 0.004). However, there was no statistically significant difference in the post-operative complications between the LDAPR and APR groups. Finally, LDAPR led to a significantly improved 2-year OS and a reduced LR compared to APR. CONCLUSION: LDAPR reduces CMR, ITP and LR and simplified the perineum operation, subsequently protecting the pelvic autonomic nerves. Compared to the conventional APR, LDAPR is a promising procedure worth adopting for rectal cancer treatment.

Multi-imaging platform for rhizosphere studies: Phosphorus and oxygen fluxes.

Rhizosphere is a soil volume of high spatio-temporal heterogeneity and intensive plant-soil-microbial interactions, for which visualization and process quantification is of highest scientific and applied relevance, but still very challenging. A novel methodology for quick assessment of two-dimensional distribution of available phosphorus (P) in rhizosphere was suggested, tested, and development up to the application platform. Available P was firstly trapped by an in-situ diffusive gradients in thin-films (DGT) sampler with precipitated zirconia as the binding gel, and subsequently, the loaded gel was analyzed with an optimized colorimetric imaging densitometry (CID). The imaging platform was established linking: i) DGT, ii) planar optode, and iii) soil zymography techniques to simultaneously determine available P, oxygen, and acid phosphatase in rhizosphere at sub-millimeter spatial scales. The DGT identified available P level in rice rhizosphere were spatially overlapping to the localized redox hotspots and phosphatase activity. The spatial relationship between available P and acid phosphatase activity was dependent on root development. The root radial oxygen loss (ROL) remained active during the experimental observations (2-3 days), while a flux of available P of 10 pg cm-2 s-1 was visualized within 2-3 mm of roots, confirming the correlative response of rice roots to oxygen secretion and P uptake. Summarizing, the established imaging platform is suitable to capture spatial heterogeneity and temporal dynamics of root activities, nutrient bioavailability, ROL and enzyme activities in rhizosphere.

Effects of Manganese and Iron, Alone or in Combination, on Apoptosis in BV2 Cells.

The aim of study was to address the effects of manganese and iron, alone and in combination, on apoptosis of BV2 microglia cells, and to determine if combined exposure to these metals augments their individual toxicity. We used a murine microglial BV2 cell line. Cell cytotoxicity was analyzed by propidium iodide (PI) exclusion assay. Cell ROS production was analyzed by 2', 7'-dichlorofluorescin diacetate (DCFH-DA) probe staining. Pro-inflammatory cytokine production was monitored by ELISA. Cell apoptosis was analyzed by PE Annexin V/7-AAD staining. Mitochondrial membrane integrity was analyzed by flow cytometry. We used immunoblotting to analyze the effect of manganese, iron alone, or their combined exposure on the activation of caspase9, P53, Bax, and Bcl2 apoptosis signaling pathways. Caspase3 activity was determined using a Colorimetric. Manganese, iron, and their combined exposure for 24 h induced the activation of BV2 microglia cells and increased ROS production and the expression of the inflammatory cytokines, IL-1ß and TNF-α. And we also found that the apoptosis rate increased, mitochondrial membrane potential decreased, apoptosis-related proteins caspase9, P53, Bax, and Bcl2 expression increased, and caspase3 activity increased. Furthermore, we found that combined manganese-iron cytotoxicity was lower than that induced by manganese exposure alone. Manganese, iron alone, or their combination exposure can induce apoptosis in glial cells. Iron can reduce the toxicity of manganese, and there is an antagonistic effect between manganese and iron.

Patterns and drivers of avian taxonomic and phylogenetic beta diversity in China vary across geographical backgrounds and dispersal abilities.

Geographical background and dispersal ability may strongly influence assemblage dissimilarity; however, these aspects have generally been overlooked in previous large-scale beta diversity studies. Here, we examined whether the patterns and drivers of taxonomic beta diversity (TBD) and phylogenetic beta diversity (PBD) of breeding birds in China vary across (1) regions on both sides of the Hu Line, which demarcates China's topographical, climatic, economic, and social patterns, and (2) species with different dispersal ability. TBD and PBD were calculated and partitioned into turnover and nestedness components using a moving window approach. Variables representing climate, habitat heterogeneity, and habitat quality were employed to evaluate the effects of environmental filtering. Spatial distance was considered to assess the impact of dispersal limitation. Variance partitioning analysis was applied to assess the relative roles of these variables. In general, the values of TBD and PBD were high in mountainous areas and were largely determined by environmental filtering. However, different dominant environmental filters on either side of the Hu Line led to divergent beta diversity patterns. Specifically, climate-driven species turnover and habitat heterogeneity-related species nestedness dominated the regions east and west of the line, respectively. Additionally, bird species with stronger dispersal ability were more susceptible to environmental filtering, resulting in more homogeneous assemblages. Our results indicated that regions with distinctive geographical backgrounds may present different ecological factors that lead to divergent assemblage dissimilarity patterns, and dispersal ability determines the response of assemblages to these ecological factors. Identifying a single universal explanation for the observed pattern without considering these aspects may lead to simplistic or incomplete conclusions. Consequently, a comprehensive understanding of large-scale beta diversity patterns and effective planning of conservation strategies necessitate the consideration of both geographical background and species dispersal ability.

Hepatic arterial infusion therapy for advanced hepatocellular carcinoma after systemic treatment failure: Multicenter, real-world study.

AIM: The study was conducted to evaluate the feasibility and safety profile of hepatic arterial infusion chemotherapy with oxaliplatin, 5-fluorouracil, and leucovorin (HAIC-FOLFOX) as an alternative therapeutic choice for patients with advanced hepatocellular carcinoma (HCC) that is refractory to systemic treatment including immune checkpoint blockades or molecular targeting agents. METHODS: Two hundred and forty five consecutive patients with advanced HCC who received HAIC-FOLFOX treatment after systemic treatment failure were retrospectively reviewed in six institutions and their survival, tumor response, and tolerance were assessed. RESULTS: The median overall survival (OS) and progression-free survival of the 209 included participants were 10.5 months (95% confidence interval [CI], 8.1-12.9) and 6.0 months (95% CI, 5.1-6.9), respectively. According to Response Evaluation Criteria in Solid Tumors 1.1 criteria, the objective response rate was 21.1%, and the disease control rate was 64.6%. Multivariate analysis of risk factors of OS were albumin-bilirubin grade (2 and 3 vs. 1, hazard ratio [HR] 1.57; 95% CI, 1.05-2.34; p = 0.028), tumor number (>3 vs. 1-3, HR 2.18; 95% CI, 1.10-4.34; p = 0.026), extrahepatic spread (present vs. absent, HR 1.61, 95% CI, 1.06-2.45; p = 0.027), synchronous systemic treatment (present vs. absent, HR 0.55, 95% CI, 0.37-0.83; p = 0.004) and treatment response (responder vs. nonresponder, HR 0.30, 95% CI, 0.17-0.53; p < 0.001). Grade 3-4 adverse events (AEs) occurred in 59 (28.2%) HCC patients. All AEs were manageable, and deaths related to hepatic artery infusion chemotherapy treatment were not observed. CONCLUSIONS: Our findings support the effectiveness and safety of HAIC-FOLFOX treatment for patients with advanced HCC who have failed systemic treatment.

Combined exposure to manganese and iron decreases oxidative stress-induced nerve damage by increasing Nrf2/HO-1/NQO1 expression.

BACKGROUND: Manganese (Mn) and iron (Fe) are essential trace elements for humans, yet excessive exposure to Mn or Fe can accumulate in the central nervous system (CNS) and cause neurotoxicity. The purpose of this study was to investigate the effects of Mn and Fe exposure, alone or in combination, on inducing oxidative stress-induced neurological damage in rat cortical and SH-SY5Y cells, and to determine whether combined exposure to these metals increases their individual toxicity. METHODS: SH-SY5Y cells and male Sprague-Dawley rats were used to observe the effects of oxidative stress-induced neurological damage induced by exposure to manganese and iron alone or in combination. To detect the expression of anti-oxidative stress-related proteins, Nrf2, HO-1, and NQO1, and the apoptosis-related proteins, Bcl2 and Bax, and the neurological damage-related protein, α-syn. To detect reactive oxygen species generation and apoptosis. To detect the expression of the rat cortical protein Nrf2. To detect the production of proinflammatory cytokines. RESULTS: We demonstrate that juvenile developmental exposure to Mn and Fe and their combination impairs cognitive performance in rats by inducing oxidative stress causing neurodegeneration in the cortex. Mn, Fe, and their combined exposure increased the expression of ROS, Bcl2, Bax, and α-syn, activated the inflammatory factors IL-6 and IL-12, inhibited the activities of SOD and GSH, and induced oxidative stress-induced neurodegeneration both in rats and SH-SY5Y cells. Combined Mn-Fe exposure attenuated the oxidative stress induced by Mn and Fe exposure alone by increasing the expression of antioxidant factors Nrf2, HO-1, and NQO1. CONCLUSION: In both in vivo and in vitro studies, manganese and iron alone or in combination induced oxidative stress, leading to neuronal damage. In contrast, combined exposure to manganese and iron mitigated the oxidative stress induced by exposure to manganese and iron alone by increasing the expression of antioxidant factors. Therefore, studies to elucidate the main causes of toxicity and establish the molecular mechanisms of toxicity should help to develop more effective therapeutic modalities in the future.