Cardiovascular events in crush syndrome: on-site therapeutic strategies and pharmacological investigations.

Crush syndrome often occurs after severe crush injury caused by disasters or accidents, and is associated with high mortality and poor prognosis. Cardiovascular complications, such as cardiac arrest, hypovolemic shock, and hyperkalemia-related cardiac dysfunction, are the primary causes of on-site death in crush syndrome. Prehospital evaluation, together with timely and correct treatment, is of great benefit to crush syndrome patients, which is difficult in most cases due to limited conditions. Based on current data and studies, early fluid resuscitation remains the most important on-site treatment for crush syndrome. Novel solutions and drugs used in fluid resuscitation have been investigated for their effectiveness and benefits. Several drugs have proven effective for the prevention or treatment of cardiovascular complications in crush syndrome, such as hypovolemic shock, hyperkalemia-induced cardiac complications, myocardial ischemia/reperfusion injury, ventricular dysfunction, and coagulation disorder experimentally. Moreover, these drugs are beneficial for other complications of crush syndrome, such as renal dysfunction. In this review, we will summarize the existing on-site treatments for crush syndrome and discuss the potential pharmacological interventions for cardiovascular complications to provide clues for clinical therapy of crush syndrome.

NF-кB promotes aggresome formation via upregulating HDAC6 and in turn maintaining Vimentin cage.

Proteasome inhibitors have been applied to anticancer therapy by accumulating toxic misfolded proteins. However, chemical inactivation of proteasome generates aggresome, a Vimentin cage-enclosed subcellular structure quarantining HDAC6-Dynein-transported misfolded proteins before the protein toxicants are degraded by autophagy. Hence, aggresome may attenuate proteasome inhibitor drugs-induced cytotoxicity. To solve the problem, it is imperative to characterize how cells assemble aggresome. By examining aggresomes in six cell lines, A549 cells were selectively studied for their bigger cell size and moderate aggresome forming activity. Aggresome grew in size upon continuous exposure of A549 cells to proteasome inhibitor MG132, and reached a mature size around 16th to 24th hour of treatment. Mechanistic studies revealed that NF-кB translocated to nucleus in MG132 treated cells, and chemical activation or knockdown of NF-кB enhanced or prohibited aggresome assembly. Further analyses showed that NF-кB upregulated HDAC6, and HDAC6 maintained Vimentin cage by interacting with Vimentin p72, a key modification of the intermediate filament contributing to aggresome formation. Remarkably, chemical inactivation of NF-кB synergized MG132-induced cell mortality. All the findings suggest that NF-кB dictates aggresome assembly via upregulating HDAC6, and NF-кB inhibitor may serve as a potential drug potentiating proteasome inhibitor medicine-induced cytotoxicity during the treatment of cancer cells.

Biomechanical effects of a new crimpable gate spring combined with conventional rectangular archwires for torque adjustment of individual anterior teeth : A comparative finite element study.

OBJECTIVE: Precise root torque adjustment of anterior teeth is indispensable for optimizing dental esthetics and occlusal stability in orthodontics. The efficiency of traditional rectangular archwire manipulation within bracket slots seems to be limited. The crimpable gate spring, a novel device, has emerged as a promising alternative. Yet, there is a paucity of guidelines for its optimal clinical application. This study used finite element analysis (FEA) to investigate the biomechanical impact of the gate spring on torque adjustment of individual anterior teeth and to elucidate the most effective application strategy. METHODS: A FEA model was constructed by a maxillary central incisor affixed with an edgewise bracket featuring a 0.022â€¯× 0.028 inch (in) slot. A range of stainless steel rectangular archwires, in conjunction with a gate spring, were modeled and simulated within the bracket slots. A control group utilized a conventional rectangular wire devoid of a gate spring. Palatal root moments were standardized to 9, 18, and 36 Nmm for both experimental and control groups. RESULTS: The gate spring significantly amplified palatal root movement, notably with the 0.019â€¯× 0.025 in archwire. However, this was accompanied by an increase in stress on the tooth and periodontal ligament, particularly in the cervical regions. The synergistic use of a 0.019â€¯× 0.025 in rectangular archwire with a gate spring in a 0.022â€¯× 0.028 in bracket slot was identified as most efficacious for torque control of individual anterior teeth. CONCLUSIONS: The gate spring is a viable auxiliary device for enhancing torque adjustment on individual teeth. However, caution is advised as excessive initial stress may concentrate in the cervical and apical regions of the periodontal ligament and tooth.

Quantitative comparison of CSVD imaging markers between patients with possible amyloid small vessel disease and with non-amyloid small vessel disease.

The spatial distribution patterns of cerebral microbleeds are associated with different types of cerebral small vessel disease (CSVD). This study aims to examine the disparities in brain imaging markers of CSVD among patients diagnosed with possible amyloid and non-amyloid small vessel disease. The head MR scans including susceptibility-weighted imaging (SWI) sequences from 351 patients at our institute were collected for analysis. CSVD imaging markers were quantified or graded across various CSVD dimensions in the patient images. Patients were categorized into the cerebral amyloid angiopathy group (CAA), hypertensive arteriopathy group (HA), or mixed small vessel disease group (Mixed), based on the spatial distribution of microbleeds. White matter lesions (WML) were segmented using an artificial neural network and assessed via a voxel-wise approach. Significant differences were observed among the three groups in several indices: microbleed count, lacune count at the centrum semiovale and basal ganglia levels, grade of enlarged perivascular space (EPVS) at the basal ganglia, and white matter lesion volume. These indices were substantially higher in the Mixed group compared to the other groups. Additionally, the incidences of cerebral hemorrhages (χ2 = 7.659, P = 0.006) and recent small subcortical infarcts (χ2 = 4.660, P = 0.031) were significantly more frequent in the HA group than in the CAA group. These results indicate that mixed spatial distribution patterns of microbleeds demonstrated the highest burden of cerebral small vessel disease. Microbleeds located in the deep brain regions were associated with a higher incidence of recent small subcortical infarcts and cerebral hemorrhages compared to those in the cortical areas.

Tryptophan regulates the expression of IGFBP1 in bovine endometrial epithelial cells in vitro via the TDO2-AHR pathway.

BACKGROUND: This study aimed to identify the roles of L-tryptophan (Trp) and its rate-limiting enzymes on the receptivity of bovine endometrial epithelial cells. Real-time PCR was conducted to analyze the differential expression of genes between different groups of bovine endometrial epithelial cells. Western blot was performed to detect Cyclooxygenase-2 (COX2) expression after treatment with Trp or kynurenine (the main metabolites of Trp). The kynurenine assay was used to examine if Trp or prostaglandin E2 (PGE2) can increase the production of kynurenine in the bovine endometrial epithelial cells. RESULTS: Trp significantly stimulates insulin growth factor binding protein 1 (IGFBP1) expression, a common endometrial marker of conceptus elongation and uterus receptivity for ruminants. When bovine endometrial epithelial cells are treated with Trp, tryptophan hydroxylase-1 remains unchanged, but tryptophan 2,3-dioxygenase 2 (TDO2) is significantly increased, suggesting tryptophan is mainly metabolized through the kynurenine pathway. Kynurenine significantly stimulates IGFBP1 expression. Furthermore, Trp and kynurenine significantly increase the expression of aryl hydrocarbon receptor (AHR). CH223191, an AHR inhibitor, abrogates the induction of Trp and kynurenine on IGFBP1. PGE2 significantly induces the expression of TDO2, AHR, and IGFBP1. CONCLUSIONS: The regulation between Trp / kynurenine and PGE2 may be crucial for the receptivity of the bovine uterus.

Identification of AS1842856 as a novel small-molecule GSK3α/ß inhibitor against Tauopathy by accelerating GSK3α/ß exocytosis.

Glycogen synthase kinase-3α/ß (GSK3α/ß) is a critical kinase for Tau hyperphosphorylation which contributes to neurodegeneration. Despite the termination of clinical trials for GSK3α/ß inhibitors in Alzheimer's disease (AD) treatment, there is a pressing need for novel therapeutic strategies targeting GSK3α/ß. Here, we identified the compound AS1842856 (AS), a specific forkhead box protein O1 (FOXO1) inhibitor, reduced intracellular GSK3α/ß content in a FOXO1-independent manner. Specifically, AS directly bound to GSK3α/ß, promoting its translocation to the multivesicular bodies (MVBs) and accelerating exocytosis, ultimately decreasing intracellular GSK3α/ß content. Expectedly, AS treatment effectively suppressed Tau hyperphosphorylation in cells exposed to okadaic acid or expressing the TauP301S mutant. Furthermore, AS was visualized to penetrate the blood-brain barrier (BBB) using an imaging mass microscope. Long-term treatment of AS enhanced cognitive function in P301S transgenic mice by mitigating Tau hyperphosphorylation through downregulation of GSK3α/ß expression in the brain. Altogether, AS represents a novel small-molecule GSK3α/ß inhibitor that facilitates GSK3α/ß exocytosis, holding promise as a therapeutic agent for GSK3α/ß hyperactivation-associated disorders.

Management strategies and outcomes in pregnancy-related acute aortic dissection: a multicentre cohort study in China.

BACKGROUND: Acute aortic dissection (AD) in pregnancy poses a lethal risk to both mother and fetus. However, well-established therapeutic guidelines are lacking. This study aimed to investigate clinical features, outcomes and optimal management strategies for pregnancy-related AD. METHODS: We conducted a retrospective multicentre cohort study including 67 women with acute AD during pregnancy or within 12 weeks postpartum from three major cardiovascular centres in China between 2003 and 2021. Patient characteristics, management strategies and short-term outcomes were analysed. RESULTS: Median age was 31 years, with AD onset at median 32 weeks gestation. Forty-six patients (68.7%) had type A AD, of which 41 underwent immediate surgery. Overall maternal mortality was 10.4% (7/67) and fetal mortality was 26.9% (18/67). Compared with immediate surgery, selective surgery was associated with higher risk of composite maternal and fetal death (adjusted RR: 12.47 (95% CI 3.26 to 47.73); p=0.0002) and fetal death (adjusted RR: 8.77 (95% CI 2.33 to 33.09); p=0.001). CONCLUSIONS: Immediate aortic surgery should be considered for type A AD at any stage of pregnancy or postpartum. For pregnant women with AD before fetal viability, surgical treatment with the fetus in utero should be considered. Management strategies should account for dissection type, gestational age, and fetal viability. TRIAL REGISTRATION NUMBER: NCT05501145.

Astrocyte-derived lactoferrin inhibits neuronal ferroptosis by reducing iron content and GPX4 degradation in APP/PS1 transgenic mice.

Increased astrocytic lactoferrin (Lf) expression was observed in the brains of elderly individuals and Alzheimer's disease (AD) patients. Our previous study revealed that astrocytic Lf overexpression improved cognitive capacity by facilitating Lf secretion to neurons to inhibit ß-amyloid protein (Aß) production in APP/PS1 mice. Here, we further discovered that astrocytic Lf overexpression inhibited neuronal loss by decreasing iron accumulation and increasing glutathione peroxidase 4 (GPX4) expression in neurons within APP/PS1 mice. Furthermore, human Lf (hLf) treatment inhibited ammonium ferric citrate (FAC)-induced ferroptosis by chelating intracellular iron. Additionally, machine learning analysis uncovered a correlation between Lf and GPX4. hLf treatment boosted low-density lipoprotein receptor-related protein 1 (LRP1) internalization and facilitated its interaction with heat shock cognate 70 (HSC70), thereby inhibiting HSC70 binds to GPX4, and eventually attenuating GPX4 degradation and FAC-induced ferroptosis. Overall, astrocytic Lf overexpression inhibited neuronal ferroptosis through two pathways: reducing intracellular iron accumulation and promoting GPX4 expression via inhibiting chaperone-mediated autophagy (CMA)-mediated GPX4 degradation. Hence, upregulating astrocytic Lf expression is a promising strategy for combating AD.

Expression and significance of CEMIP and CYP11B2 in serum in women with foetal growth restriction.

BACKGROUND: Foetal growth restriction (FGR) occurs when a foetus fails to reach its growth potential. This observational study assessed the expression and significance of cell migration-including protein (CEMIP) and aldosterone synthase (CYP11B2) in the serum of pregnant women with FGR. METHODS: 40 singleton FGR-suffered pregnant women, as well as 40 normal singleton pregnant women, were enrolled. The expression of CEMIP and CYP11B2 in serum was detected in early pregnancy. The correlations between parameters were evaluated. The predictive variables for FGR were determined. The diagnostic value of CEMIP and CYP11B2 for FGR was analysed. RESULTS: CEMIP and CYP11B2 mRNA expression in the serum of pregnant women with FGR decreased (both P < 0.001). CEMIP (95%CI: 0.802-0.921, P < 0.001) and CYP11B2 (95%CI: 0.795-0.907, P < 0.001) mRNA expression in serum and soluble fms like tyrosine kinase-1 (sFLT1)/placental growth factor (PlGF) ratio (95%CI: 0.866-0.974, P < 0.001) were independent predictors of FGR, and CEMIP (r = -0.578, P = 0.001) and CYP11B2 (r = -0.602, P < 0.001) mRNA expression in serum were negatively correlated with sFLT1/PlGF ratio. CEMIP (AUC = 0.741) and CYP11B2 (AUC = 0.764) mRNA expression in serum had good diagnostic value for FGR. CONCLUSION: The expression of CEMIP and CYP11B2 is reduced in the serum of pregnant women with FGR and may become new diagnostic markers for FGR.

Foetal growth restriction is the inability of the foetus to reach its growth potential in the uterus due to various factors. This study aimed to investigate the expression and significance of cell migration-including protein and aldosterone synthase in serum of pregnant women with foetal growth restriction. In our study, we found that the expression of cell migration-including protein and aldosterone synthase in serum of pregnant women with foetal growth restriction were decreased. Cell migration-including protein and aldosterone synthase expression was negatively correlated with soluble fms like tyrosine kinase-1/placental growth factor ratio. In addition, the study also found that cell migration-including protein and aldosterone synthase expression in serum had good diagnostic value for foetal growth restriction.

Cognitive impairment and depression precede increased HDL-C levels in middle-aged and older Chinese adults: cross-lagged panel analyses.

BACKGROUND: High-density lipoprotein cholesterol (HDL-C) is widely recognized for its protective effects against cognitive decline. However, recent studies have presented conflicting results, with some suggesting no significant cognitive benefits or even an increased risk of dementia associated with high HDL-C levels. For those who suffer from depression, the cognitive benefits of HDL-C may be diminished or reversed. The purpose of this study is to investigate the associations between HDL-C, cognitive ability, and depressive symptoms in middle-aged and older Chinese adults. METHODS: The datasets utilized were sourced from the China Health and Retirement Longitudinal Study (CHARLS) for the years 2011 and 2015, comprising 4,302 participants. Cross-lagged models were employed to explore the temporal sequence between cognitive performance and HDL-C levels, and to examine the interplay among depression, cognition, and HDL-C. Confounding factors such as sociodemographic characteristics, sleep conditions, and history of chronic diseases were controlled for. RESULTS: The analysis revealed unidirectional effects of baseline impaired cognition and greater severity of depression on increased HDL-C levels at follow-up (ß = - 0.036 and ß = 0.028, respectively, P < 0.05). However, higher baseline HDL-C levels did not significantly predict cognitive performance or depression 4 years later (ß = - 0.008 and ß = 0.023, respectively, P > 0.05). Depressive symptoms and cognition were found to have a significant bidirectional association (ß = - 0.026 and ß = - 0.053, respectively, P < 0.05). CONCLUSIONS: Cognitive impairment and depression are associated with higher HDL-C levels, whereas higher HDL-C levels do not appear to protect against cognitive decline or depressive symptoms. These findings underscore the importance of preserving cognitive and mental health, which may lower the likelihood of cardiovascular disease and dementia. Future studies should validate these findings and develop targeted interventions tailored to specific populations.

Revealing the links between hair metal(loids) and alterations in blood pressure among children in e-waste recycling areas through urinary metabolomics.

Hypertension is prevalent in e-waste recycling areas, and elevated blood pressure in children significantly increases the risk of hypertension in adulthood. However, the associations and toxic pathways between chronic exposure to metal(loids) and elevated blood pressure are rarely investigated. In this study, we measured the levels of 29 hair metal(loids) (chronic exposure biomarkers) and blood pressure in 667 susceptible children from an e-waste recycling area to explore their relationships. Paired urine metabolomics analysis was also performed to interpret potential mechanistic pathways. Results showed that the hypertension prevalence in our recruited children (13.0 %) exceeded the average rate (9.5 %) for Chinese children aged 6-17 years. The top five abundant metal(loids), including lead, strontium, barium, and zinc, demonstrated the most profound associations with elevated systolic blood pressure. Quantile g-computation, weighted quantile sum, and Bayesian kernel machine regression analysis jointly demonstrated a significant association between chronic exposure to metal(loids) mixture and systolic blood pressure. Interestingly, selenium showed significant antagonistic interactions with these four metals, suggesting that supplementing selenium may help children resist the elevated blood pressure induced by metal(loids) exposure. Increased metal(loids) and blood pressure levels were significantly linked to changes in urine metabolomics. Structural equation model indicated that androsterone glucuronide and N-Acetyl-1-aspartylglutamic acid were the significant mediators of the associations between metal(loids) and blood pressure, with mediation effects of 77.4 % and 29.0 %, respectively, suggesting that androsterone glucuronide and N-Acetyl-1-aspartylglutamic acid may be involved in the development of metal-induced blood pressure elevating effect. Girls were more vulnerable to metal(loids)-induced hormonal imbalance, especially androsterone glucuronide, than boys. Chronic exposure to metal(loids) at e-waste recycling sites may contribute to elevated blood pressure in children through disrupting various metabolism pathways, particularly hormonal balance. Our study provides new insights into potential mechanistic pathways of metal(loids)-induced changes in children's blood pressure.

Trade-off between soil enzyme activities and hotspots area depends on long-term fertilization: In situ field zymography.

Mineral fertilizers and livestock manure have been found to impact soil enzyme activities and distributions, but their trade-off and subsequent effects on soil functioning related to nutrient cycling are rarely evaluated. Here, we investigated the long-term effects of manure and mineral fertilization on the spatial distribution of enzyme activities related to carbon, nitrogen, and phosphorus cycling under field-grown maize. We found that the legacy of mineral fertilizers increased the rhizosphere extension for ß-glucosidase and N-acetylglucosaminidase by 16-170 %, and the hotspots area by 37-151 %, compared to manure. The legacy of manure, especially combined with mineral fertilizers, increased enzyme activities and formed non-rhizosphere hotspots. Furthermore, we found a trade-off between hotspots area and enzyme activities under the legacy effect of long-term fertilization. This suggested that plants and microorganisms regulate nutrient investments by altering spatial distribution of enzyme activities. The positive correlation between hotspots area and nutrient contents highlights the importance of non-rhizosphere hotspots induced by manure in maintaining soil fertility. Compared to mineral fertilization, the legacy effect of manure expanded the soil functions for nutrient cycling in both rhizosphere and non-rhizosphere by >1.7 times. In conclusion, the legacy of manure expands non-rhizosphere hotspots and enhances soil functioning, while mineral fertilization expands rhizosphere extension and intensifies hotspots area for nutrient exploitation.

Analysis of Clinical Diagnosis and Treatment Modes for Congenital Branchial Cleft Anomalies.

OBJECTIVE: The objective of this study was to investigate and assess the clinical data of 123 patients diagnosed with congenital branchial cleft anomalies (CBCAs), to summarize pivotal aspects concerning their clinical diagnosis and treatment process. MATERIALS AND METHODS: The authors conducted a retrospective analysis of 123 patients who underwent surgical intervention for CBCAs at our institution between August 2005 and September 2021. The clinical demographic characteristics of the patients, primary symptoms, treatment chronology, preoperative diagnostic assessments, surgical strategies, occurrences of postoperative complications, and rates of recurrence were subjected to statistical analysis. RESULTS: Among the enrolled patients, there were 43 cases (34.9%) of congenital first branchial cleft anomalies (CFBCA), 76 cases (61.8%) of congenital second branchial cleft anomalies (CSBCA), and 4 cases (3.3%) of congenital third branchial cleft anomalies (CTBCA), with no cases of congenital fourth branchial anomalies (CFBA). Notably, among all cases, 43 anomalies were situated in the upper one-third of the sternocleidomastoid muscle, while 80 anomalies were located in the lower one-third. Different surgical approaches were selected for patients based on the specific type of anomaly presented. Following surgery, there was recurrence in 14 cases, with factors such as patient age, clinical categorization, lesion type, and history of preoperative infection and surgical intervention identified as primary risk factors for it. CONCLUSION: CBCAs represent comparatively uncommon disorders affecting the head and cervical regions in clinical practice. Diagnostic modes such as ultrasonography and lipiodol contrast radiography can be used for accurate diagnosis, with surgical intervention serving as the primary therapeutic method.

A Mitogen-Activated Protein Kinase Pathway Is Required for Bacillus amyloliquefaciens PMB05 to Enhance Disease Resistance to Bacterial Soft Rot in Arabidopsis thaliana.

When a plant is infected by a pathogen, endogenous immune responses are initiated. When the initiation of these defense responses is induced by a pathogen-associated molecular pattern (PAMP) of a pathogen, it is called PAMP-triggered immunity (PTI). Previous studies have shown that Bacillus amyloliquefaciens PMB05 can enhance PTI signals and improve disease control of bacterial soft rot and wilt in Arabidopsis thaliana. In the context of controlling bacterial wilt disease, the involvement of a mitogen-activated protein kinase (MAPK) signaling pathway has been established. Nevertheless, it remains unclear whether this pathway is also required for B. amyloliquefaciens PMB05 in controlling bacterial soft rot. In this study, A. thaliana ecotype Columbia (Col-0) and its mutants on a MAPK pathway-related pathway were used as a model and established that the ability of B. amyloliquefaciens PMB05 to control soft rot requires the participation of the MAPK pathway. Moreover, the enhancement of disease resistance by PMB05 is highly correlated with the activation of reactive oxygen species generation and stomata closure, rather than callose deposition. The spray inoculation method was used to illustrate that PMB05 can enhance stomatal closure, thereby restricting invasion by the soft rot bacterium. This control mechanism has also been demonstrated to require the activation of the MAPK pathway. This study demonstrates that B. amyloliquefaciens PMB05 can accelerate stomata closure via the activation of the MAPK pathway during PTI, thereby reducing pathogen invasion and achieving disease resistance against bacterial soft rot.

Comprehensive analysis of the m6A demethylase FTO in endothelial dysfunction by MeRIP sequencing.

N6-methyladenosine (m6A) is the most general post-transcriptional modification of eukaryotic mRNAs and long-stranded non-coding RNAs. In this process, It has been shown that FTO associates with the m6A mRNA demethylase and plays a role in diabetic vascular endothelial dysfunction. In the present study, we detected FTO protein expression in HUVECs by Western blot and found that FTO was highly expressed in all disease groups relative to the control group. To explore the mechanism of FTO in T2DM vasculopathy, we performed an analysis by methylated RNA immunoprecipitation sequencing (MeRIP-seq) to elucidate the role of aberrant m6A modification and mRNA expression in endothelial dysfunction. The results showed 202 overlapping genes with varying m6A modifications and varied mRNA expression, and GO and KEGG enrichment analysis revealed that these genes were predominantly enriched in pathways associated with T2DM complications and endothelial dysfunction. By an integrated analysis of MeRIP-seq and RNA-seq results, the IGV plots showed elevated kurtosis of downstream candidate gene modifications, which may be downstream targets for FTO to exercise biological functions. HOXA9 and PLAU mRNA expression levels were significantly down after FTO inhibition. In the current work, we set up a typological profile of the m6A genes among HUVECs as well as uncovered a hidden relationship between RNA methylation modifications for T2DM vasculopathy-associated genes. Taken together, this study indicates that endothelial functional impairment is present in T2DM patients and may be related to aberrant expression of FTO.

Associations between Patient-Generated Subjective Global Assessment criteria and all-cause mortality among cancer patients: Evidence from baseline and longitudinal analyses.

OBJECTIVES: The prognostic effects of the Patient-Generated Subjective Global Assessment (PG-SGA) criteria in cancer survivors have been observed but require validation in clinical practice. This study was designed to evaluate the prognostic effects of baseline and longitudinal changes in PG-SGA scores on all-cause mortality among Chinese cancer patients in a real-world setting. METHODS: Study patients were selected from one representative tertiary hospital in West China. Kaplan-Meier curves and Cox regression analyses were used to estimate the prognostic effect of baseline and dynamic changes in PG-SGA scores on the all-cause mortality of cancer patients. Receiver operating characteristic curves and a concordance index were used to evaluate the predictive accuracy of PG-SGA criteria. RESULTS: A total of 1415 cancer patients were included in this study, with a mean age of 46 years old. Cox regression analysis showed that baseline malnourished status was significantly associated with the survival of cancer patients (PG-SGA 4-8: hazard ratio [HR] = 1.46, 95% confidence interval [CI]: 1.09-1.96, P = 0.012; PG-SGA ≥9: HR = 1.78, 95% CI: 1.34-2.37, P < 0.001). Cancer patients with longitudinal increased PG-SGA scores (>2 points) were observed to have high risks for mortality (HR = 1.69, 95% CI: 1.04-2.74, P = 0.033). Compared with longitudinal changes in PG-SGA scores, baseline malnourished status showed higher predictive power in identifying the risk subgroup (concordance index: 0.646 vs. 0.586). Sensitivity analyses supported the main findings. CONCLUSIONS: This study highlights the prognostic value of baseline and dynamic changes in PG-SGA scores for cancer patients, which can help improve their outcomes.

A Rapid Method for Screening Pathogen-Associated Molecular Pattern-Triggered Immunity-Intensifying Microbes.

PAMP-triggered immunity (PTI) is the first layer of plant defense response that occurs on the plant plasma membrane. Recently, the application of a rhizobacterium, Bacillus amyloliquefaciens strain PMB05, has been demonstrated to enhance flg22Pst- or harpin-triggered PTI response such as callose deposition. This PTI intensification by PMB05 further contributes to plant disease resistance to different bacterial diseases. Under the demand for rapid and large-scale screening, it has become critical to establish a non-staining technology to identify microbial strains that can enhance PTI responses. Firstly, we confirmed that the expression of the GSL5 gene, which is required for callose synthesis, can be enhanced by PMB05 during PTI activation triggered by flg22 or PopW (a harpin from Ralstonia solanacearum). The promoter region of the GSL5 gene was further cloned and fused to the coding sequence of gfp. The constructed fragments were used to generate transgenic Arabidopsis plants through a plant transformation vector. The transgenic lines of AtGSL5-GFP were obtained. The analysis was performed by infiltrating flg22Pst or PopW in one homozygous line, and the results exhibited that the green fluorescent signals were observed until after 8 h. In addition, the PopW-induced fluorescent signal was significantly enhanced in the co-treatment with PMB05 at 4 h after inoculation. Furthermore, by using AtGSL5-GFP to analyze 13 Bacillus spp. strains, the regulation of PopW-induced fluorescent signal was observed. And, the regulation of these fluorescent signals was similar to that performed by callose staining. More importantly, the Bacillus strains that enhance PopW-induced fluorescent signals would be more effective in reducing the occurrence of bacterial wilt. Taken together, the technique by using AtGSL5-GFP would be a promising platform to screen plant immunity-intensifying microbes to control bacterial wilt.

Impact of frailty on postoperative outcomes after hepatectomy: A systematic review and meta-analysis.

BACKGROUND: The impact of frailty on postoperative outcomes in patients undergoing hepatectomy is still unclear. AIM: To study the influence of frailty on postoperative outcomes, such as mortality, rate of complications, and length of hospitalization, following hepatectomy. METHODS: PubMed, EMBASE, and Scopus databases were searched for observational studies with adult (≥ 18 years) patients after planned/elective hepatectomy. A random-effects model was used for all analyses, and the results are expressed as weighted mean difference (WMD), relative risk (RR), or hazards ratio (HR) with 95% confidence interval (CI). RESULTS: Analysis of the 13 included studies showed a significant association of frailty with elevated risk of in-hospital mortality (RR = 2.76, 95%CI: 2.10-3.64), mortality at 30 d (RR = 4.60, 95%CI: 1.85-11.40), and mortality at 90 d (RR = 2.52, 95%CI: 1.70-3.75) in the postoperative period. Frail patients had a poorer long-term survival (HR = 2.89, 95%CI: 1.84-4.53) and higher incidence of "any" complications (RR = 1.69, 95%CI: 1.40-2.03) and major (grade III or higher on the Clavien-Dindo scale) complications (RR = 2.69, 95%CI: 1.85-3.92). Frailty was correlated with markedly lengthier hospital stay (WMD = 3.65, 95%CI: 1.45-5.85). CONCLUSION: Frailty correlates with elevated risks of mortality, complications, and prolonged hospitalization, which need to be considered in surgical management. Further research is essential to formulate strategies for improved outcomes in this vulnerable cohort.

Advances in the mechanism of small nucleolar RNA and its role in DNA damage response.

Small nucleolar RNAs (snoRNAs) were previously regarded as a class of functionally conserved housekeeping genes, primarily involved in the regulation of ribosome biogenesis by ribosomal RNA (rRNA) modification. However, some of them are involved in several biological processes via complex molecular mechanisms. DNA damage response (DDR) is a conserved mechanism for maintaining genomic stability to prevent the occurrence of various human diseases. It has recently been revealed that snoRNAs are involved in DDR at multiple levels, indicating their relevant theoretical and clinical significance in this field. The present review systematically addresses four main points, including the biosynthesis and classification of snoRNAs, the mechanisms through which snoRNAs regulate target molecules, snoRNAs in the process of DDR, and the significance of snoRNA in disease diagnosis and treatment. It focuses on the potential functions of snoRNAs in DDR to help in the discovery of the roles of snoRNAs in maintaining genome stability and pathological processes.

Comparative biomechanical analysis of four different tooth- and bone-borne frog appliances for molar distalization : A three-dimensional finite element study.

PURPOSE: The purpose of this study was to analyze the biomechanical effects of four different designs of frog appliances for molar distalization using finite element analysis. METHODS: A three-dimensional finite element model including complete dentition, periodontal ligament, palatine, and alveolar bone was established. Four types of frog appliances were designed to simulate maxillary molar distalization: tooth-button-borne (Type A), bone-borne (Type B), bone-button-borne (Type C), and tooth-bone-borne (Type D) frog appliances. A force of 10 N was applied simulating a screw in the anteroposterior direction. To assess the von Mises stress distribution and the resultant displacements in the teeth and periodontal tissues, geometric nonlinear theory was utilized. RESULTS: Compared to the conventional tooth-borne frog appliance (Type A), the bone-borne frog appliances showed increased first molar distalization with enhanced mesiolingual rotation and distal tipping, but the labial inclination and intrusion of the incisors were insignificant. When replacing the palatal acrylic button with miniscrews (Types B and D), more anchorage forces were transmitted from the first premolar to palatine bone, which was further dispersed by the assistance of a palatal acrylic button (Type C). CONCLUSIONS: Compared to tooth-borne frog appliances, the bone-borne variants demonstrated a clear advantage for en masse molar distalization. The combined anchorage system utilizing palatal acrylic buttons and miniscrews (Type C) offers the most efficient stress distribution, minimizing force concentration on the palatine bone.