The clinical efficacy of combined ESA and Roxadustat treatment for renal anemia in hemodialysis patients with secondary hyperparathyroidism: A case series.

RATIONALE: Pharmacological mechanism of Roxadustat in the treatment of renal anemia. PATIENT CONCERNS: To investigate the efficacy and safety of combined Roxadustat and erythropoiesis stimulator (ESA) treatment of renal anemia in hemodialysis patients with secondary hyperparathyroidism. DIAGNOSES: A retrospective analysis was conducted on hemodialysis patients with renal anemia and secondary hyperparathyroidism treated with ESAs alone, who were admitted to our hospital from March 2022 to December 2022. INTERVENTIONS: The patients were treated with Roxadustat combined with ESAs for 3 months, during which oral iron supplementation was given, and the changes in Hb levels and laboratory-related indicators before and after the combined treatment were analyzed. OUTCOMES: The results showed that a total of 13 patients received combination therapy, with a significant increase in Hb compared to ESAs alone (t = -3.955, P = .002). The Hb qualification rate was 38.46%, and the ∆Hb response rate was 76.92%. The parathyroid hormone significantly decreased with a statistically significant difference (Z = -2.062b, P = .039). Hemoglobin (RBC), total iron binding capacity, and serum ferritin (male) were significantly increased compared to ESAs alone. Total cholesterol and low-density lipoprotein were significantly lower than ESAs alone. The differences in the changes in the above indicators were statistically significant (P < .05). There was no statistically significant difference in changes in other laboratory-related indicators (P > .05). No adverse reactions were observed during the combined treatment of 13 patients. LESSONS SUBSECTIONS: The combination of Roxadustat and ESAs can effectively improve renal anemia in hemodialysis patients with secondary hyperparathyroidism, as well as improve indicators of hyperparathyroidism and blood lipid levels with high levels of safety. This combined treatment thus provides a new and safe treatment method for these patients.

Reliability of Metformin's protective effects against doxorubicin-induced cardiotoxicity: a meta-analysis of animal studies.

Background: The protective effects of metformin (Met) against doxorubicin (Dox)-induced cardiotoxicity via potential hypotheses of mechanisms of action with unknown reliability and credibility. Objectives: This study aimed to investigate the protective effects of Met against Dox-induced cardiotoxicity and the underlying mechanisms of action, as well as examine their reliability and credibility. Methods: A comprehensive search was conducted within the PubMed, Embase, Web of Science, Science Direct, Scopus, and CNKI databases from inception to 31 December 2023. Animal experiments evaluating the efficacy of Met against Dox-induced cardiotoxicity were included in this study. The primary efficacy outcomes were markers of myocardial injury. Effect size was measured using the standardized mean difference for continuous variables. Data were pooled using a random-effects model in the Stata 18 statistical software package. Results: Twenty-one studies involving 203-208 animals treated with Dox and 271-276 animals treated with Dox and Met were included in this analysis. Quality assessment revealed high-quality scores. Pooled results favored Met treatment based on the serum lactate dehydrogenase (LDH), creatine kinase-myocardial band (CK-MB), cardiac troponin I (cTnI), and aspartate aminotransferase levels. Sensitivity analysis using the leave-one-out method demonstrated stable results. Funnel plots, Egger's test, and Begg's test confirmed potential publication bias. The oxidative stress hypothesis has been investigated extensively based on abundant evidence. Conclusion: Met is effective and safe for protecting against Dox-induced cardiotoxicity, thus making it an appropriate drug for clinical investigation. The oxidative stress hypothesis of mechanism of action is well established with highest reliability and credibility.

Association between dietary carotenoid intakes and the risk of asthma in children and adolescents: evidence from the National Health and Nutrition Examination Survey 2007-2016.

Background: In recent years, the incidence of asthma in children has been increasing. As a chronic disease, in addition to drug treatment, dietary management is also important. However, studies of carotenoids and asthma have shown mixed results. This study aimed to evaluate whether the relationship between carotenoid intake and current asthma holds significant importance. Methods: We studied 9,118 children aged 6-16 years in the National Health and Nutrition Examination Survey (NHANES) of US from 2007 to 2016, and the relationship of dietary carotenoid and its subgroup with pediatric asthma. Current asthma was assessed by parent-reported, doctor-diagnosed, asthma using a standardized questionnaire. We used multivariate logistic regression to calculate the odds ratio (OR) for current asthma with a 95% confidence interval (CI). Results: Total carotenoid intake was not associated with the risk of current asthma. Compared with the first quantile, the second quantile of ß-cryptoxanthin intake was positively correlated with current asthma (Q2: 1.227; 95% CI: 1.025-1.470; P=0.03). The test of trend showed that, as the α-carotene intake increased, the risk of current asthma showed a decreasing trend, which was very close to the statistic confidence cutoff (Model I: P for trend =0.001; Model II: P for trend =0.003; Model III: P for trend =0.08). In subgroup analysis, family history of asthma interacted with carotenoid intake (P=0.005). The population without a family history of asthma, there were significant negative associations between carotenoid intakes and asthma (quartile 4: Model III: 0.720; 95% CI: 0.549-0.943; P=0.02). Conclusions: In this study, pediatric current asthma was not related to total carotenoids in our total participants. Total dietary carotenoid intake has a protective effect on children without a family history of asthma. Meanwhile, ß-cryptoxanthin intake is positively correlated with asthma.

Periprostatic adipose tissue inhibits tumor progression by secreting apoptotic factors: A natural barrier induced by the immune response during the early stages of prostate cancer.

Prostate cancer (PCa) is the second most prevalent malignancy in men worldwide. The risk factors for PCa include obesity, age and family history. Increased visceral fat has been associated with high PCa risk, which has prompted previous researchers to investigate the influence of body composition and fat distribution on PCa prognosis. However, there is a lack of studies focusing on the mechanisms and interactions between periprostatic adipose tissue (PPAT) and PCa cells. The present study investigated the association between the composition of pelvic adipose tissue and PCa aggressiveness to understand the role played by this tissue in PCa progression. Moreover, PPAT-conditioned medium (CM) was prepared to assess the influence of the PPAT secretome on the pathophysiology of PCa. The present study included 50 patients with localized PCa who received robot-assisted radical prostatectomy. Medical records were collected, magnetic resonance imaging scans were analyzed and body compositions were calculated to identify the associations between adipose tissue volume and clinical PCa aggressiveness. In addition, CM was prepared from PPAT and perivesical adipose tissue (PVAT) collected from 25 patients during surgery, and its effects on the PCa cell lines C4-2 and LNCaP, and the prostate epithelial cell line PZ-HPV-7, were investigated using a cell proliferation assay and RNA sequencing (RNA-seq). The results revealed that the initial prostate-specific antigen level was significantly correlated with pelvic and periprostatic adipose tissue volumes. In addition, PPAT volume was significantly higher in patients with extracapsular tumor extension. PCa cell proliferation was significantly reduced when the cells were cultured in PPAT-CM compared with when they were cultured in control- and PVAT-CM. RNA-seq revealed that immune responses, and the cell death and apoptosis pathways were enriched in PPAT-CM-cultured cells indicating that the cytokines or other factors secreted from PPAT-CM induced PCa cell apoptosis. These findings revealed that the PPAT secretome may inhibit PCa cell proliferation by activating immune responses and promoting cancer cell apoptosis. This mechanism may act as a first-line defense during the early stages of PCa.

[Rapid determination of chlorate and perchlorate in tea by ion exchange chromatography-tandem mass spectrometry].

Ion exchange chromatography-tandem mass spectrometry (IEC-MS/MS) has recently become the preferred method for detecting ionic substances in tea. In this study, an IEC-MS/MS method was developed for the rapid determination of chlorate and perchlorate residues in tea samples. The optimal sample extraction process, pretreatment column, and chromatographic and mass spectrometric conditions were systematically investigated. In the optimal process, the tea samples were ultrasonically extracted with methanol-water (13∶7, v/v), and a PRiME HLB SPE column was used to purify the sample extract. An AceChrom Hybri-A IEC column (150 mm×2.1 mm, 5.0 µm) was used for separation, and 100 mmol/L ammonium acetate-acetonitrile (40∶60, v/v) was used as the mobile phase for isocratic elution. The flow rate was 0.3 mL/min, the column temperature was 40 ℃, and the injection volume was 5.0 µL. The mass spectrometric data were collected in negative electrospray ionization mode combined with multiple reaction monitoring (MRM) mode to achieve the rapid and accurate separation and qualitative analysis of the desired chemical components. Quantification was performed using the internal standard (IS) method. The measurement results showed a good linear relationship when the mass concentrations of chlorate and perchlorate were between 2.00-200 and 1.00-100 µg/L, respectively, with correlation coefficients (r2) greater than 0.9990. The average recoveries of chlorate and perchlorate at three spiked levels of low, medium, and high ranged from 88.54% to 97.25% with relative standard deviations (RSDs, n=7) of 3.2%-5.2%. The limits of detection for chlorate and perchlorate were 12.0 and 8.0 µg/kg, respectively, while the limits of quantification were 40.0 and 26.6 µg/kg, respectively. The results of tests conducted to assess the linearity, specificity, accuracy, precision, and applicability of the method to the analysis of chlorate and perchlorate in 15 tea samples collected from a local market demonstrated its validity for the routine analysis of tea samples. The proposed method is simple, rapid, sensitive, and accurate, and can meet requirements for the rapid screening and quantitative analysis of residual trace chlorate and perchlorate in large quantities of tea samples.

Convergence and divergence in neurostructural signatures of unipolar and bipolar depressions: Insights from surface-based morphometry and prospective follow-up.

BACKGROUND: Bipolar disorder (BD) is often misidentified as unipolar depression (UD) during its early stages, typically until the onset of the first manic episode. This study aimed to explore both shared and unique neurostructural changes in patients who transitioned from UD to BD during follow-up, as compared to those with UD. METHODS: This study utilized high-resolution structural magnetic resonance imaging (MRI) to collect brain data from individuals initially diagnosed with UD. During the average 3-year follow-up, 24 of the UD patients converted to BD (cBD). For comparison, the study included 48 demographically matched UD patients who did not convert and 48 healthy controls. The MRI data underwent preprocessing using FreeSurfer, followed by surface-based morphometry (SBM) analysis to identify cortical thickness (CT), surface area (SA), and cortical volume (CV) among groups. RESULTS: The SBM analysis identified shared neurostructural characteristics between the cBD and UD groups, specifically thinner CT in the right precentral cortex compared to controls. Unique to the cBD group, there was a greater SA in the right inferior parietal cortex compared to the UD group. Furthermore, no significant correlations were observed between cortical morphological measures and cognitive performance and clinical features in the cBD and UD groups. LIMITATIONS: The sample size is relatively small. CONCLUSIONS: Our findings suggest that while cBD and UD exhibit some common alterations in cortical macrostructure, numerous distinct differences are also present. These differences offer valuable insights into the neuropathological underpinnings that distinguish these two conditions.

Correlation between Circle of Willis configuration and intracranial arterial dolichoectasia, and genetic contributions.

OBJECTIVES: Intracranial arterial dolichoectasia (IADE) is characterized by the dilation, elongation, and tortuosity of intracranial arteries. We aimed to investigate the association between variations of the Circle of Willis (COW) and IADE in the general population, as well as estimate the genetic correlation between COW variations and IADE. METHODS: A total of 981 individuals from a population-based cohort were included. Brain magnetic resonance angiography was performed to assess COW variants and measure the diameters of intracranial arteries. IADE was defined as a total intracranial volume-adjusted diameter ≥ 2 standard deviations. Logistic regression models were used to analyze the association between COW variations and IADE. The heritability and genetic correlation were estimated using genome-wide complex trait analysis (GCTA) based on single nucleotide polymorphism (SNP) array data. RESULTS: The prevalence of IADE was 6.2 %. Hypoplastic/absent A1 segments were associated with an increase in contralateral ICA diameter (ß ± SE, 0.279 ± 0.049; p = 0.001) and a decrease in ipsilateral ICA diameter (ß ± SE, -0.300 ± 0.050; p = 0.001). Fetal-type posterior cerebral artery (FTP) was associated with a larger ICA diameter (ß ± SE, 0.326 ± 0.048; p = 0.001) and a smaller BA diameter (ß ± SE, -0.662 ± 0.043; p = 0.001). FTP revealed a positive genetic correlation with ICA dilation (rG = 0.259 ± 0.175; p = 0.0009) and a negative genetic correlation with BA dilation (rG = -0.192 ± 0.153, p = 0.015). CONCLUSIONS: There was an association between COW variations and larger intracranial arterial diameters in the general population. Genetic factors may play a role in the development of intracranial arterial dilation and the formation of COW variants.

Colonic stenting: is the bridge to surgery worth its cost? A cost-effectiveness analysis at a single Asian institution.

Purpose: In patients with acute left-sided colonic obstruction, stenting can convert an emergency operation into a semi-elective procedure. However, its use continues to be debated. We performed a cost-effective analysis using our institution's experiences. Methods: Endoscopic, surgical, and financial details were prospectively collected for patients who presented with acute colonic obstruction and underwent stenting between 2019 and 2022. Outcomes were defined as technical/clinical success and successful surgical resection. The financial cost of stenting was compared with the expected cost without stenting. Results: Forty patients were included, with 29 undergoing definitive resection. The most common pathology was primary colon cancer (27 patients, 93%). Endoscopic stenting had high technical (90%) and clinical (83%) success rates, with low rates of complications such as perforation (2 patients, 7%) and migration (0 patients, 0%). As a bridge to surgery, the median procedure time was 226 minutes and the surgical outcomes also showed a low rate of complications (3 patients, 11%), such as anastomotic leakage (0 patients, 0%), intraabdominal abscesses (2 patients, 7%), and 30-day postoperative mortality (0 patients, 0%). The cumulative costs with colonic stenting were $32,900, while the expected costs with emergency surgery, including stoma reversal, were $40,700 (healthcare cost-savings of $7,800 per person). The difference was mainly due to the avoidance of upfront emergency surgery. The incremental cost-effectiveness ratio was 0.81, favoring colonic stenting over upfront emergency surgery. Conclusion: Colonic stenting as a bridge to surgery is safe and cost-effective for treating left-sided colonic obstruction with high success rates and low complication rates.

Small vessel disease burden and prognosis of recent subcortical ischaemic stroke differ by parent artery atherosclerosis.

BACKGROUND AND PURPOSE: Parent artery atherosclerosis is an important aetiology of recent subcortical ischaemic stroke (RSIS). However, comparisons of RSIS with different degrees of parent artery atherosclerosis are lacking. METHODS: Prospectively collected data from our multicentre cohort (all were tertiary centres) of the Stroke Imaging Package Study between 2015 and 2017 were retrospectively reviewed. The patients with RSIS defined as a single clinically relevant diffusion-weighted imaging positive lesion in the territory of lenticulostriate arteries were categorized into three subgroups: (1) normal middle cerebral artery (MCA) on magnetic resonance angiography and high-resolution magnetic resonance imaging (HR-MRI); (2) low-grade MCA atherosclerosis (normal or <50% stenosis on magnetic resonance angiography and with MCA plaques on HR-MRI); (3) steno-occlusive MCA atherosclerosis (stenosis ≥50% or occlusion). The primary outcome was 90-day functional dependence (modified Rankin Scale score >2). The clinical and imaging findings were compared between subgroups. RESULTS: A total of 239 patients (median age 60.0 [52.0-67.0] years, 72% male) were enrolled, including 140 with normal MCA, 64 with low-grade MCA atherosclerosis and 35 with steno-occlusive MCA atherosclerosis. Patients with steno-occlusive MCA atherosclerosis had the largest infarct volume. Low-grade MCA atherosclerosis was independently associated with cerebral microbleeding, more severe perivascular spaces in basal ganglia and higher total cerebral small vessel disease burden. Low-grade MCA atherosclerosis was an independent determinant of 90-day functional dependence (odds ratio 3.897; 95% confidence interval 1.309-11.604). CONCLUSIONS: Our study suggested RSIS with varying severity of parent artery atherosclerosis exhibits distinctive clinical and neuroimaging characteristics, with low-grade MCA atherosclerosis associating with higher cerebral small vessel disease burden and worse prognosis.

Fast Determination of Eleven Food Additives in River Water Using C18 Functionalized Magnetic Organic Polymer Nanocomposite Followed by High-Performance Liquid Chromatography.

A novel magnetic nanomaterial with Fe3O4 as the core, PS-DVB as the shell layer, and the surface modified with C18 (C18-PS-DVB-Fe3O4) had been synthesized by seeded emulsion polymerization. C18-PS-DVB-Fe3O4 retains the advantages of the chemical stability, large porosity, and uniform morphology of organic polymers and has the magnetic properties of Fe3O4. A simple, flexible, and efficient magnetic dispersive solid phase extraction (Mag-dSPE) method for the extraction of preservatives, sweeteners, and colorants in river water was established. C18-PS-DVB-Fe3O4 was used as an adsorbent for Mag-dSPE and was coupled with high-performance liquid chromatography (HPLC) to detect 11 food additives: acesulfame, amaranth, benzoic acid, tartrazine, saccharin sodium, sorbic acid, dehydroacetic acid, sunset yellow, allura red, brilliant blue, and erythrosine. Under the optimum extraction conditions, combined with ChromCoreTMAQC18 (5 µm, 4.6 × 250 mm), 20 mmol/L ammonium acetate aqueous solution and methanol were used as mobile phases, and the detection wavelengths were 240 nm and 410 nm. The limits of detection (LODs) of 11 food additives were 0.6-3.1 µg/L with satisfactory recoveries ranging from 86.53% to 106.32%. And the material could be reused for five cycles without much sacrifice of extraction efficiency. The proposed method has been used to determine food additives in river water samples, and results demonstrate the applicability of the proposed C18-PS-DVB-Fe3O4 Mag-dSPE coupled with the HPLC method to environment monitoring analysis.

Electroacupuncture activates the peroxisome proliferators-activated receptor pathway to improve the phenotype of cerebral palsy.

AIM: This study explores the efficacy of electroacupuncture (EA) in treating cerebral palsy (CP) in Sprague-Dawley (SD) pups, specifically CP animal models, and its molecular mechanisms. METHODS: Gait analysis and Y-maze were used to detect the improvement of motor ability and cognitive function of CP rats after EA treatment. Transcription sequencing was used to determine the key pathway for EA to improve the symptoms of CP. PPAR agonists were used to verify the causal relationship between the pathway and the improvement of CP phenotype. RESULTS: The motor ability and cognitive function of CP pups were improved after EA treatment. The results of transcriptome sequencing suggest that the improvement of CP phenotype may be caused by the activation of PPAR pathway. PPAR pathway is widely activated in the epithelium of CP pups treated with EA, which is verified by qPCR. Rosiglitazone (Ros), a PPAR agonist, can improve CP phenotype while activating PPAR pathway, which proves the causal relationship between PPAR pathway activation and CP phenotype improvement. CONCLUSION: Our study demonstrated behavioral improvements and enhanced cognitive functions in CP models after EA treatment by activating PPAR pathway, suggesting new perspectives for CP rehabilitation, and providing theoretical support for acupuncture treatment of CP.

Evolving pathways towards water security in the Vietnamese Mekong Delta: An adaptive management perspective.

The interplay of climate change, upstream hydropower development, and local water engineering interventions for agricultural production contributes substantially to the transformation of waterscapes and water scarcity in the Vietnamese Mekong Delta. This paper aims to examine how these dynamics are linked to the paradigm shift in water management in An Giang and Ben Tre, the two ecologically distinct provinces that face serious water scarcity in the delta. We used the adaptive management concept to examine how state-led policy directions from food security towards water security enable change in water management that gives priority to water retention. While policy learning is evident, questions remain about how this ad-hoc solution could help address the presently acute water scarcity and water security over the long term. The paper advocates achieving water security should focus not only on diplomatic interventions into upstream climate-development complexities but also local water-livelihood politics.

Effects of vitrectomy combined with internal limiting membrane peeling in patients with diabetic macular edema.

BACKGROUND: Diabetic macular edema (DME), a chronic microvascular complication of diabetes, is a leading cause of visual impairment and blindness. Pars plana vitrectomy (PPV) can restore the normal macular structure and reduce macular edema, whereas internal limiting membrane (ILM) peeling is used to treat tractional macular diseases. Despite the advantages, there is limited research on the combined effects of PPV with ILM peeling. AIM: To observe the effects of PPV combined with ILM peeling on postoperative central macular thickness (CMT), best-corrected visual acuity (BCVA), cystoid macular edema (CME) volume, and complications in patients with DME. METHODS: Eighty-one patients (92 eyes) diagnosed with DME at the Beijing Shanqu Liangxiang Hospital between January and December 2022 were randomly divided to undergo PPV alone (control group: 41 patients, 47 eyes) or PPV + ILM peeling (stripping group: 40 patients, 45 eyes); a single surgeon performed all surgeries. The two groups were compared preoperatively and 1 and 3 months postoperatively. RESULTS: Preoperatively, both groups had comparable values of CMT, BCVA, and CME volume (P > 0.05). After surgery (both 1 and 3 months), both groups showed significant reductions in CMT, BCVA, and CME volume compared to preoperative levels, with the stripping group showing more significant reductions compared to the control group (P < 0.05). Further repeated-measures ANOVA analysis for within-group differences revealed significant effects of group and time, and interaction effects for CMT, BCVA, and CME volume (P < 0.05). There were no significant differences in the incidence of complications between the groups (retinal detachment: control = 2, stripping = 1; endophthalmitis: Control = 4, stripping = 1; no cases of secondary glaucoma or macular holes; χ 2 = 0.296, P = 0.587). CONCLUSION: PPV with ILM peeling can significantly improve the visual acuity of patients with DME, reduce CMT, and improve CME with fewer complications.

[Mechanism of Modified Huoluo Xiaoling Pills against colorectal cancer based on network pharmacology, molecular docking, and experimental validation].

This study aims to predict the possible targets and related signaling pathways of Modified Huoluo Xiaoling Pills against colorectal cancer(CRC) by both network pharmacology and molecular docking and verify the mechanism of action by experiments. TCMSP was used to obtain the active ingredients and targets of Modified Huoluo Xiaoling Pills, and GeneCards, DrugBank, OMIM, and TTD were employed to acquire CRC-related targets. Cytoscape software was utilized to construct the drug-active ingredient-target network, and the STRING database was applied to establish the protein-protein interaction(PPI) network. DAVID platform was adopted to investigate the targets in terms of GO function and KEGG pathway enrichment analysis. Molecular docking was performed in AutoDock Vina. HCT 116 cells were intervened by different concentrations of Modified Huoluo Xiaoling Pills-containing serum, and CCK-8 was used to detect the proliferation inhibition of HCT 116 cells in each group. Transwell was employed to show the invasive abi-lity of HCT 116 cells, and Western blot was taken to reveal the expression levels of ß-catenin, cyclinD1, c-Myc, as well as epithelial-mesenchymal transition(EMT) marker proteins E-cadherin, N-cadherin, vimentin, MMP2, MMP7, MMP9, and TWIST in HCT 116 cells. The network pharmacological analysis yielded 242 active ingredients of Modified Huoluo Xiaoling Pills, 1 844 CRC targets, and 127 overlapping targets of CRC and Modified Huoluo Xiaoling Pills, and the signaling pathways related to CRC involved PI3K-Akt, TNF, HIF-1, IL-17, Wnt, etc. Molecular docking showed that the key active ingredients had a stable binding conformation with the core proteins. CCK-8 indicated that Modified Huoluo Xiaoling Pills significantly inhibited the proliferation of HCT 116 cells. Transwell assay showed that with increasing concentration of Modified Huoluo Xiaoling Pills containing serum, the invasive ability of HCT 116 cells was more obviously inhibited. The expression of ß-catenin, cyclinD1, c-Myc, N-cadherin, vimentin, MMP2, MMP7, MMP9, and TWIST proteins were suppressed, and the expression of E-cadherin was improved by the intervention of drug-containing serum. Thus, it can be seen that Modified Huoluo Xiaoling Pills restrains the proliferation, invasion, and metastasis of CRC cells through multiple components, multiple targets, and multiple pathways, and the mechanism of action may be related to the inhibition of the activation of the Wnt/ß-catenin signaling pathway, thereby affecting the occurrence of EMT.

G protein-coupled receptor kinase 2 as a novel therapeutic target for gland fibrosis of Sjögren's syndrome.

Sjogren's syndrome (SS) is a chronic, progressive autoimmune disorder characterized by gland fibrosis. We previously found a close correlation between gland fibrosis and the expression of G protein-coupled receptor kinase 2 (GRK2). In this study we explored the pathological and therapeutic significance of GRK2 in SS. Submandibular gland (SMG) antigen-induced SS mouse model was established in WT and GRK2+/- mice. We showed that the expression levels of GRK2 were significantly up-regulated in glandular tissue and positively correlated with fibrotic morphology in SS patients and mice. Hemizygous knockout of GRK2 significantly inhibited the gland fibrosis. In mouse salivary gland epithelial cells (SGECs), we demonstrated that GRK2 interacted with Smad2/3 to positively regulate the activation of TGF-ß-Smad signaling with a TGF-ß-GRK2 positive feedback loop contributing to gland fibrosis. Hemizygous knockout of GRK2 attenuated TGF-ß-induced collagen I production in SGECs in vitro and hindered gland fibrosis in murine SS though preventing Smad2/3 nuclear translocation. Around 28 days post immunization with SMG antigen, WT SS mice were treated with a specific GRK2 inhibitor paroxetine (Par, 5 mg·kg-1·d-1, i.g. for 19 days). We found that Par administration significantly attenuated gland fibrosis and alleviated the progression of SS in mice. We conclude that genetic knockdown or pharmacological inhibition of GRK2 significantly attenuates gland fibrosis and alleviates the progression of SS. GRK2 binds to Smad2/3 and positively regulates the activation of TGF-ß-Smad signaling. A TGF-ß-GRK2 positive feedback loop contributes to gland fibrosis. Our research points out that GRK2 could be a promising therapeutic target for treating SS.

Automated diffusion-weighted image analysis along the perivascular space index reveals glymphatic dysfunction in association with brain parenchymal lesions.

Brain glymphatic dysfunction is critical in neurodegenerative processes. While animal studies have provided substantial insights, understandings in humans remains limited. Recent attention has focused on the non-invasive evaluation of brain glymphatic function. However, its association with brain parenchymal lesions in large-scale population remains under-investigated. In this cross-sectional analysis of 1030 participants (57.14 ± 9.34 years, 37.18% males) from the Shunyi cohort, we developed an automated pipeline to calculate diffusion-weighted image analysis along the perivascular space (ALPS), with a lower ALPS value indicating worse glymphatic function. The automated ALPS showed high consistency with the manual calculation of this index (ICC = 0.81, 95% CI: 0.662-0.898). We found that those with older age and male sex had lower automated ALPS values (ß = -0.051, SE = 0.004, p < .001, per 10 years, and ß = -0.036, SE = 0.008, p < .001, respectively). White matter hyperintensity (ß = -2.458, SE = 0.175, p < .001) and presence of lacunes (OR = 0.004, 95% CI < 0.002-0.016, p < .001) were significantly correlated with decreased ALPS. The brain parenchymal and hippocampal fractions were significantly associated with decreased ALPS (ß = 0.067, SE = 0.007, p < .001 and ß = 0.040, SE = 0.014, p = .006, respectively) independent of white matter hyperintensity. Our research implies that the automated ALPS index is potentially a valuable imaging marker for the glymphatic system, deepening our understanding of glymphatic dysfunction.

Analytical and experimental analysis of concrete temperature and energy considering open-air environmental variations.

Longwave radiation is an important open-air environmental factor that can significantly affect the temperature of concrete, but it has often been ignored in the temperature analysis of open-air concrete structures. In this article, an improved analytical model of concrete temperature was proposed by considering solar radiation, thermal convection, thermal conduction and especially longwave radiation. Temperature monitoring of an open-air concrete block was carried out to verify the proposed model and analyze the heat energy characteristics of open-air concrete. As demonstrated by the open-air experiment, under the influence of longwave radiation, the temperature at the top of the concrete block could decrease rapidly at night and even become lower than the minimum temperature at its bottom. Compared with the analytical model that ignores longwave radiation, the improved model that includes it better matches the measured temperature. According to the energy analysis, although solar radiation controls the transient variation in heat energy, the heat exchange caused by longwave radiation were more than that caused by convection on sunlit surfaces, which indicates the importance of considering longwave radiation.

Identification of male sterility-related genes in Saccharum officinarum and Saccharum spontaneum.

KEY MESSAGE: Candidate male sterility genes were identified in sugarcane, which interacts with kinase-related proteins, transcription factors, and plant hormone signaling pathways to regulate stamen and anther development. Saccharum officinarum is a cultivated sugarcane species that its predominant feature is high sucrose content in stems. Flowering is necessary for breeding new cultivars but will terminate plant growth and reduce sugar yield. The wild sugarcane species Saccharum spontaneum has robust and viable pollen, whereas most S. officinarum accessions are male sterile, which is a desirable trait of a maternal parent in sugarcane breeding. To study male sterility and related regulatory pathways in sugarcane, we carried out RNAseq using flowers in different developmental stages between male-sterile S. officinarum accession 'LA Purple' and fertile S. spontaneum accession 'SES208'. Gene expression profiles were used to detect how genes are differentially expressed between male sterile and fertile flowers and to identify candidate genes for male sterility. Weighted gene correlation networks analysis (WGCNA) was conducted to investigate the regulatory networks. Transcriptomic analyses showed that 988 genes and 2888 alleles were differentially expressed in S. officinarum compared to S. spontaneum. Ten differentially expressed genes and thirty alleles were identified as candidate genes and alleles for male sterility in sugarcane. The gene Sspon.03G0007630 and two alleles of the gene Sspon.08G0002270, Sspon.08G0002270-2B and Sspon.08G0014700-1A, were involved in the early stamen or carpel development stages, while the remaining genes were classified into the post-meiosis stage. Gibberellin, auxin, and jasmonic acid signaling pathways are involved in the stamen development in sugarcane. The results expanded our knowledge of male sterility-related genes in sugarcane and generated genomic resources to facilitate the selection of ideal maternal parents to improve breeding efficiency.

Risk factors analysis and prediction model construction for severe pneumonia in older adult patients.

Objective: Pneumonia is a common and serious infectious disease that affects the older adult population. Severe pneumonia can lead to high mortality and morbidity in this group. Therefore, it is important to identify the risk factors and develop a prediction model for severe pneumonia in older adult patients. Method: In this study, we collected data from 1,000 older adult patients who were diagnosed with pneumonia and admitted to the intensive care unit (ICU) in a tertiary hospital. We used logistic regression and machine learning methods to analyze the risk factors and construct a prediction model for severe pneumonia in older adult patients. We evaluated the performance of the model using accuracy, sensitivity, specificity, area under the receiver operating characteristic curve (AUC), and calibration plot. Result: We found that age, comorbidities, vital signs, laboratory tests, and radiological findings were associated with severe pneumonia in older adult patients. The prediction model had an accuracy of 0.85, a sensitivity of 0.80, a specificity of 0.88, and an AUC of 0.90. The calibration plot showed good agreement between the predicted and observed probabilities of severe pneumonia. Conclusion: The prediction model can help clinicians to stratify the risk of severe pneumonia in older adult patients and provide timely and appropriate interventions.