Inhibition of calcium-sensing receptor by its antagonist promotes gastrointestinal motility in a Parkinson's disease mouse model.

BACKGROUND: The Calcium-sensing receptor (CaSR) participates in the regulation of gastrointestinal (GI) motility under normal conditions and might be involved in the regulation of GI dysmotility in patients with Parkinson's disease (PD). METHODS: CaSR antagonist-NPS-2143 was applied in in vivo and ex vivo experiments to study the effect and underlying mechanisms of CaSR inhibition on GI dysmotility in the MPTP-induced PD mouse model. FINDINGS: Oral intake of NPS-2143 promoted GI motility in PD mice as shown by the increased gastric emptying rate and shortened whole gut transit time together with improved weight and water content in the feces of PD mice, and the lack of influence on normal mice. Meanwhile, the number of cholinergic neurons, the proportion of serotonergic neurons, as well as the levels of acetylcholine and serotonin increased, but the numbers of nitrergic and tyrosine hydroxylase immunoreactive neurons, and the levels of nitric oxide synthase and dopamine decreased in the myenteric plexus in the gastric antrum and colon of PD mice in response to NPS-2143 treatment. Furthermore, the numbers of c-fos positive neurons in the nucleus tractus solitarius (NTS) and cholinergic neurons in the dorsal motor nucleus of the vagus (DMV) increased in NPS-2143 treated PD mice, suggesting the involvement of both the enteric (ENS) and central (CNS) nervous systems. However, ex vivo results showed that NPS-2143 directly inhibited the contractility of antral and colonic strips in PD mice via a non-ENS mediated mechanism. Further studies revealed that NPS-2143 directly inhibited the voltage gated Ca2+ channels, which might, at least in part, explain its direct inhibitory effects on the GI muscle strips. INTERPRETATION: CaSR inhibition by its antagonist ameliorated GI dysmotility in PD mice via coordinated neuronal regulation by both ENS and CNS in vivo, although the direct effects of CaSR inhibition on GI muscle strips were suppressive.

Linewidth compression of a single longitudinal mode ytterbium-doped fiber laser based on femtosecond laser fabricated fiber Bragg gratings.

We demonstrate a single longitudinal mode distributed Bragg reflection (DBR) fiber laser by directly fabricating fiber Bragg gratings (FBGs) on an ytterbium-doped fiber (YDF) using a femtosecond laser. A simple optical self-injection feedback method was used to effectively compress the linewidth and reduce relative intensity noise (RIN) of a single longitudinal mode DBR fiber laser. Further, we investigated the effect of self-injection feedback cavity length and reflectivity on linewidth compression and determined that the linewidth tends to decrease with the increase of the external cavity photon lifetime. By a self-injection feedback, the laser linewidth was compressed from 31.8 kHz to 1.4 kHz. Meanwhile, the relaxation oscillation peak from -103.2d B/H z at 1.51 MHz was suppressed to -122.3d B/H z at 0.16 MHz. This low-noise narrow linewidth single longitudinal mode fiber laser is expected to be a promising candidate for applications such as active detection of neutral atmosphere and distributed fiber sensing.

Wearable Sensing Device Integrated with Prestored Reagents for Cortisol Detection in Sweat.

Wearable sweat sensors have achieved rapid development since they hold great potential in personalized health monitoring. However, a typical difficulty in practical processes is the control of working conditions for biorecognition elements, e.g., pH level and ionic strength in sweat may decrease the affinity between analytes and recognition elements. Here, we developed a wearable sensing device for cortisol detection in sweat using an aptamer as the recognition element. The device integrated functions of sweat collection, reagent prestorage, and signal conversion. Especially, the components of prestored reagents were optimized according to the inherent characteristics of sweat samples and electrodes, which allowed us to keep optimal conditions for aptamers. The sweat samples were transferred from the inlet of the device to the reagent prestored chamber, and the dry preserved reagents were rehydrated with sweat and then arrived at the aptamer-modified electrodes. Sweat samples of volunteers were analyzed by the wearable sensing device, and the results showed a good correlation with those of the ELISA kit. We believe that this convenient and reliable wearable sensing device has significant potential in self-health monitoring.

Association between increased systemic immune-inflammation index and postoperative delirium in older intertrochanteric fracture patients.

BACKGROUND AND PURPOSE: The systemic immune-inflammation index (SII), a novel inflammation index derived from the counts of circulating platelets, neutrophils and lymphocytes, has been studied in the treatment of acute cancer and ischemic stroke (AIS). However, the clinical value of the SII in postoperative delirium patients has not been further investigated. The purpose of our research was to study the incidence and preoperative risk factors for postoperative delirium (POD) and verify whether the SII could serve as a potential marker for POD in older intertrochanteric fracture patients. Finally, we created a novel nomogram for predicting POD in older patients with intertrochanteric fractures. METHODS: We enrolled elderly patients with intertrochanteric fractures who underwent proximal femoral nail antirotation (PFNA) between February 2021 and April 2023. Univariate and multivariate logistic analyses were subsequently performed to confirm the risk factors and construct a nomogram model.Calibration curve and clinical decision curve analysis (DCA) were used to assess the model's fitting performance. The performance of the nomogram was evaluated for discrimination, calibration, and clinical utility. RESULTS: A total of 293 patients were eligible for inclusion in the study, 25.6% (75/293) of whom had POD. The POD patients had higher SII values than the non-POD patients. The SII was strongly correlated with POD in older intertrochanteric fracture patients, and the optimal cutoff value was 752.6 × 109. Multivariate analysis revealed that age, diabetes, total albumin, SII > 752.6 × 109 and a CRP > 20.25 mg/L were independent risk factors for POD patients. By incorporating these 5 factors, the model achieved a concordance index of 0.745 (95% CI, 0.683-0.808) and had a well-fitted calibration curve and good clinical application value. CONCLUSION: The SII is a simple and valuable biomarker for POD, and the new nomogram model can be used to accurately predict the occurrence of POD. They can be utilized in clinical practice to identify those at high risk of POD in older intertrochanteric fracture patients.

A long non-coding RNA functions as a competitive endogenous RNA to modulate TaNAC018 by acting as a decoy for tae-miR6206.

Increasing evidence indicates a strong correlation between the deposition of cuticular waxes and drought tolerance. However, the precise regulatory mechanism remains elusive. Here, we conducted a comprehensive transcriptome analysis of two wheat (Triticum aestivum) near-isogenic lines, the glaucous line G-JM38 rich in cuticular waxes and the non-glaucous line NG-JM31. We identified 85,143 protein-coding mRNAs, 4,485 lncRNAs, and 1,130 miRNAs. Using the lncRNA-miRNA-mRNA network and endogenous target mimic (eTM) prediction, we discovered that lncRNA35557 acted as an eTM for the miRNA tae-miR6206, effectively preventing tae-miR6206 from cleaving the NAC transcription factor gene TaNAC018. This lncRNA-miRNA interaction led to higher transcript abundance for TaNAC018 and enhanced drought-stress tolerance. Additionally, treatment with mannitol and abscisic acid (ABA) each influenced the levels of tae-miR6206, lncRNA35557, and TaNAC018 transcript. The ectopic expression of TaNAC018 in Arabidopsis also improved tolerance toward mannitol and ABA treatment, whereas knocking down TaNAC018 transcript levels via virus-induced gene silencing in wheat rendered seedlings more sensitive to mannitol stress. Our results indicate that lncRNA35557 functions as a competing endogenous RNA to modulate TaNAC018 expression by acting as a decoy target for tae-miR6206 in glaucous wheat, suggesting that non-coding RNA has important roles in the regulatory mechanisms responsible for wheat stress tolerance.

Probiotics for inflammatory bowel disease: Is there sufficient evidence?

Inflammatory bowel disease (IBD) refers to chronic inflammatory disorders of the gut. Ulcerative colitis (UC) and Crohn's disease (CD) are two subtypes of IBD. Evidence suggests that the intestinal microbiota plays a role in the pathogenesis of IBD, so probiotics have garnered a lot of interest as a potential treatment or prevention for IBD. However, clinical evidence of the efficacy of probiotics is still debatable. We performed a literature review. An advanced search considered clinical studies on probiotic for IBD from inception to 2023 in PubMed, Embase, Cochrane Library, and Web of Science. In the treatment of UC with probiotics, only Escherichia coli Nissle 1917 for maintenance treatment of UC in remission, and Bifidobacterium and VSL#3 for induction of remission in patients with mild to moderately active UC have shown strong evidence. Currently, there are no definitive conclusions regarding the effectiveness of probiotics in CD. The mechanism of probiotic treatment for IBD may be related to reducing oxidative stress, repairing the intestinal barrier, regulating intestinal flora balance, and modulating intestinal immune response. Differences in the benefits of probiotics between CD and UC may be attributable to the different lesion extent and immune-mediated pathophysiology. More robust randomized clinical trials are required to validate the efficacy and safety of diverse probiotic strains in IBD.

TaoHe ChengQi decoction ameliorates sepsis-induced cardiac dysfunction through anti-ferroptosis via the Nrf2 pathway.

BACKGROUND: Sepsis-induced cardiac dysfunction (SICD) is a serious complication of sepsis that is associated with increased mortality. Ferroptosis has been reported in the SICD. TaoHe ChengQi decoction (THCQD), a classical traditional Chinese medicinal formula, has multiple beneficial pharmacological effects. The potential effects of THCQD on the SICD remain unknown. PURPOSE: To investigate the effect of THCQD on SICD and explore whether this effect is related to the regulation of myocardial ferroptosis through nuclear factor erythroid 2-related factor 2 (Nrf2) activation. METHODS: We induced sepsis in a mouse model using cecal ligation and puncture (CLP) and administered THCQD (2 and 4 g/kg) and dexamethasone (40 mg/kg). Mice mortality was recorded and survival curves were plotted. Echocardiography, hematoxylin and eosin staining, and analysis of serum myocardial injury markers and inflammatory factors were used to evaluate cardiac pathology. Myocardial ferroptosis was detected by quantifying specific biomarker content and protein levels. Through HPLC-Q-Exactive-MS analysis, we identified the components of the THCQD. Network pharmacology analysis and Cellular Thermal Shift Assay (CETSA) were utilized to predict the targets of THCQD for treating SICD. We detected the expression of Nrf2 using Western blotting or immunofluorescence. An RSL3-induced ferroptosis model was established using neonatal rat cardiomyocytes (NRCMs) to further explore the pharmacological mechanism of THCQD. In addition to measuring cell viability, we observed changes in NRCM mitochondria using electron microscopy and JC-1 staining. NRF2 inhibitor ML385 and Nrf2 knockout mice were used to validate whether THCQD exerted protective effects against SICD through Nrf2-mediated ferroptosis signaling. RESULTS: THCQD reduced mortality in septic mice, protected against CLP-induced myocardial injury, decreased systemic inflammatory response, and prevented myocardial ferroptosis. Network pharmacology analysis and CETSA experiments predicted that THCQD may protect against SICD by activating the Nrf2 signaling pathway. Western blotting and immunofluorescence showed that THCQD activated Nrf2 in cardiac tissue. THCQDs consistently mitigated RSL3-induced ferroptosis in NRCM, which is related to Nrf2. Furthermore, the pharmacological inhibition of Nrf2 and genetic Nrf2 knockout partially reversed the protective effects of THCQD on SICD and ferroptosis. CONCLUSION: The effect of THCQD on SICD was achieved by activating Nrf2 and its downstream pathways.

[Effect and mechanism of Linggui Zhugan Decoction in regulating Sig1R on Angâ ¡-induced cardiomyocyte hypertrophy].

This study aims to explore the mechanism of Linggui Zhugan Decoction(LGZGD) in inhibiting Angiotensin Ⅱ(AngⅡ)-induced cardiomyocyte hypertrophy by regulating sigma-1 receptor(Sig1R). The model of H9c2 cardiomyocyte hypertrophy induced by AngⅡ in vitro was established by preparing LGZGD-containing serum and blank serum. H9c2 cells were divided into normal group, AngⅡ model group, 20% normal rat serum group(20% NSC), and 20% LGZGD-containing serum group. After the cells were incubated with AngⅡ(1 µmol·L~(-1)) or AngⅡ with serum for 72 h, the surface area of cardiomyocytes was detected by phalloidine staining, and the activities of Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase were detected by micromethod. The mitochondrial Ca~(2+) levels were detected by flow cytometry, and the expression levels of atrial natriuretic peptide(ANP), brain natriuretic peptide(BNP), Sig1R, and inositol 1,4,5-triphosphate receptor type 2(IP_3R_2) were detected by Western blot. The expression of Sig1R was down-regulated by transfecting specific siRNA for investigating the efficacy of LGZGD-containing serum on cardiomyocyte surface area, Na~+-K~+-ATPase activity, Ca~(2+)-Mg~(2+)-ATPase activity, mitochondrial Ca~(2+), as well as ANP, BNP, and IP_3R_2 protein expressions. The results showed that compared with the normal group, AngⅡ could significantly increase the surface area of cardiomyocytes and the expression of ANP and BNP(P<0.01), and it could decrease the activities of Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase, the concentration of mitochondrial Ca~(2+), and the expression of Sig1R(P<0.01). In addition, IP_3R_2 protein expression was significantly increased(P<0.01). LGZGD-containing serum could significantly decrease the surface area of cardiomyocytes and the expression of ANP and BNP(P<0.05, P<0.01), and it could increase the activities of Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase, the concentration of mitochondrial Ca~(2+ )(P<0.01), and the expression of Sig1R(P<0.05). In addition, IP_3R_2 protein expression was significantly decreased(P<0.05). However, after Sig1R was down-regulated, the effects of LGZGD-containing serum were reversed(P<0.01). These results indicated that the LGZGD-containing serum could inhibit cardiomyocyte hypertrophy induced by AngⅡ, and its pharmacological effect was related to regulating Sig1R, promoting mitochondrial Ca~(2+ )inflow, restoring ATP synthesis, and protecting mitochondrial function.

[Mechanism of Kuntai Capsules in treatment of polycystic ovary syndrome rat models based on AGE-RAGE signal pathway].

This study aims to investigate the impact of Kuntai Capsules(KTC) on polycystic ovarian syndrome(PCOS) rat models and explore the underlying mechanism. Fifty female SD rats were randomly divided into five groups(10 rats in each group), including control group, model group, low-, medium-, and high-dose KTC group. Except for the control group, the other groups were injected with dehydroepiandrosterone(DHEA) combined with a high-fat diet(HFD) to induce the PCOS rat model for 28 days. 0.315, 0.63, and 1.26 g·kg~(-1)·d~(-1) KTC was dissolved in the same amount of normal saline and given to low-, medium-, and high-dose KTC groups by gavage. Both control group and model group were given the same amount of normal saline for 15 days. After administration, fasting blood glucose(FBG) was measured by a glucose meter. Fasting insulin(FINS), luteinizing hormone(LH), testosterone(T), and follicle-stimulating hormone(FSH) were detected by enzyme-linked immunosorbent assay(ELISA), and LH/FSH ratio and insulin resistance index(HOMA-IR) were calculated. The pathological morphology of ovarian tissue was observed by hematoxylin-eosin(HE) staining. The expression levels of collagen α type Ⅲ 1 chain(COL3A1), apoptotic factors Bax, and Bcl-2 were detected using Western blot and immunofluorescence. The mRNA expressions of COL3A1, Bax, and Bcl-2 in ovarian tissue were performed by real-time PCR(RT-PCR). The results show that compared with the control group, the body weight, serum levels of FBG, FINS, LH, T, LH/FSH, and HOMA-IR are higher in model group(P<0.05 or P<0.01), and the level of FSH is lower(P<0.05). In model group, a large number of white blood cells are found in the vaginal exfoliated cells, mainly in the interictal phase. There are more cystic prominences on the surface of the ovary. The thickness of the granular cell layer is reduced, and oocytes are absent. COL3A1 and Bax protein expression levels are increased(P<0.01), while Bcl-2 protein expression levels are decreased(P<0.05) in the ovarian tissue COL3A1 and Bax mRNA expression levels are increased in ovarian tissue(P<0.05). Compared with the model group, the body weight, FBG, FINS, LH, T, LH/FSH, and HOMA-IR in low-, medium-, and high-dose KTC groups are decreased(P<0.05 or P<0.01), while the levels of FSH in medium-, and high-dose KTC groups are increased(P<0.05 or P<0.01). Low-, medium-, and high-dose KTC groups gradually show a stable interictal phase. The surface of the ovary is smooth. Oocytes and mature follicles can be seen in ovarian tissue, and the thickness of the granular cell layer is increased. The expression level of COL3A1 protein decreases in low-and medium-dose KTC groups(P<0.05 or P<0.01), and that of Bax protein decreases in low-dose KTC group(P<0.05 or P<0.01), and the expression level of Bcl-2 protein increases in low-dose KTC group(P<0.01). The expression levels of COL3A1 and Bax mRNA decreased in the low-dose KTC group(P<0.05), while the expression levels of Bcl-2 mRNA increased(P<0.05). In summary, KTC can inhibit ovarian granulosa cell apoptosis and reduce follicular atresia by regulating the AGE-RAGE signaling pathway. It can promote insulin secretion, reduce blood sugar and body weight, restore serum hormone levels, improve symptoms of PCOS, alleviate morphological damage of the ovary, and restore ovarian function, which is of great value in the treatment of PCOS.

[Evidence map of clinical research on Chinese patent medicines for post-acute myocardial infarction heart failure].

An evidence map was established to comprehensively sort out the clinical research in the treatment of post-acute myocardial infarction heart failure(P-AMI-HF) with Chinese patent medicines, so as to reveal the distribution of evidence in this field. CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, and EMbase were searched for the randomized controlled trial(RCT), systematic reviews/Meta-analysis, and guidelines/consensus in this field. The evidence was analyzed and displayed in the form of a combination of text, charts, bubble charts, and bar charts, and the quality of RCT, systematic reviews/Meta-analysis, and guidelines/consensus were evaluated by RoB 1.0, AMSTAR2, and AGREE Ⅱ, respectively. A total of 163 RCTs, 4 systematic reviews/Meta-analysis, 1 network Meta-analysis, 2 observational studies, and 5 guidelines/consensus were included. In recent years, the total number of publications in this field has shown an upward trend. There were a variety of Chinese patent medicines in the treatment of P-AMI-HF, among which Shenfu Injection received the most attention. The clinical RCT and systematic reviews/Meta-analysis generally had poor quality, and the RCT mostly had a small size, a single center, and a short cycle. The outcome indicators mainly included cardiac function indicators, myocardial injury markers, total response rate, hemodynamic indicators, and safety indicators, while the characteristic efficacy indicators of TCM received insufficient attention. The development processes of some guidelines/consensus lack standardization, which compromised their authority and rationality. Chinese patent medicines have advantages in the treatment of P-AMI-HF, while there are also problems, which remain to be solved by more high-quality evidence. That is, more large-sample and multi-center clinical studies should be carried out in the future, and the formulation process of relevant systematic reviews/Meta-analysis and guideline/consensus should be standardized and the quality of evidence should be improved. In this way, the effectiveness and safety of Chinese patent medicines in the treatment of P-AMI-HF can be explored.

Model-based precision dosing and remedial dosing recommendations for delayed or missed doses of isoniazid in Chinese patients with tuberculosis.

AIMS: Isoniazid (INH) has been used as a first-line drug to treat tuberculosis (TB) for more than 50 years. However, large interindividual variability was found in its pharmacokinetics, and effects of nonadherence to INH treatment and corresponding remedy regime remain unclear. This study aimed to develop a population pharmacokinetic (PPK) model of INH in Chinese patients with TB to provide model-informed precision dosing and explore appropriate remedial dosing regimens for nonadherent patients. METHODS: In total, 1012 INH observations from 736 TB patients were included. A nonlinear mixed-effects modelling was used to analyse the PPK of INH. Using Monte Carlo simulations to determine optimal dosage regimens and design remedial dosing regimens. RESULTS: A 2-compartmental model, including first-order absorption and elimination with allometric scaling, was found to best describe the PK characteristics of INH. A mixture model was used to characterize dual rates of INH elimination. Estimates of apparent clearance in fast and slow eliminators were 28.0 and 11.2 L/h, respectively. The proportion of fast eliminators in the population was estimated to be 40.5%. Monte Carlo simulations determined optimal dosage regimens for slow and fast eliminators with different body weight. For remedial dosing regimens, the missed dose should be taken as soon as possible when the delay does not exceed 12 h, and an additional dose is not needed. delay for an INH dose exceeds 12 h, the patient only needs to take the next single dose normally. CONCLUSION: PPK modelling and simulation provide valid evidence on the precision dosing and remedial dosing regimen of INH.

Research on the mitigation of redeposition defects on the fused silica surface during wet etching process.

The laser-induced damage of ultraviolet fused silica optics is a critical factor that limits the performance enhancement of high-power laser facility. Currently, wet etching technology based on hydrofluoric acid (HF) can effectively eliminate absorbing impurities and subsurface defects, thereby significantly enhancing the damage resistance of fused silica optics. However, with an increase in the operating fluence, the redeposition defects generated during wet etching gradually become the primary bottleneck that restricts its performance improvement. The composition and morphology of redeposition defects were initially identified in this study, followed by an elucidation of their formation mechanism. A mitigation strategy was then proposed, which combines a reduction in the generation of precipitation with an acceleration of the precipitation dissolution process. Additionally, we systematically investigated the influence of various process parameters such as extrinsic impurity, etching depth, and megasonic excitation on the mitigation of deposition defects. Furthermore, a novel multiple-step dynamic etching method was developed. Through comprehensive characterization techniques, it has been confirmed that this new etching process not only effectively mitigate redeposition defects under low fluence conditions but also exhibits significant inhibition effects on high fluence precursors. Consequently, it significantly enhances the laser damage resistance performance of fused silica optics.

Prognostic significance of circulating tumor DNA in urothelial carcinoma: a systematic review and meta-analysis.

BACKGROUND: Circulating tumor DNA (ctDNA) has emerged as a non-invasive technique that provides valuable insights into molecular profiles and tumor disease management. This study aimed to evaluate the prognostic significance of circulating tumor DNA (ctDNA) in urothelial carcinoma (UC) through a systematic review and meta-analysis. METHODS: A comprehensive search was conducted in MEDLINE, EMBASE, and the Cochrane Library from the inception to December 2023. Studies investigating the prognostic value of ctDNA in UC were included. Hazard ratios (HRs) of disease-free survival (DFS) and overall survival (OS) were extracted. Overall meta-analysis and subgroup exploration stratified by metastatic status, ctDNA sampling time, treatment type, and detection method was performed using the R software (version 4.2.2). RESULTS: A total of sixteen studies with 1725 patients were included. Fourteen studies assessed the association between baseline ctDNA status and patient outcomes. Patients with elevated ctDNA levels exhibited significantly worse DFS (HR=6.26; 95% CI, 3.71-10.58, P<0.001) and OS (HR=4.23; 95% CI, 2.72-6.57, P<0.001) regardless of metastatic status, ctDNA sampling time, treatment type and detection methods. Six studies evaluated the prognostic value of ctDNA dynamics in UC. Patients who showed a decrease or clearance in ctDNA levels during treatment or observation demonstrated more favorable DFS (HR=0.26, 95% CI, 0.17-0.41, P<0.001) and OS (HR=0.21, 95% CI, 0.11-0.38, P<0.001) compared to those who did not. The association remained consistent across the subgroup analysis based on metastatic status and detection methods. In the immune checkpoint inhibitor-treated setting, both lower baseline ctDNA level and ctDNA decrease during the treatment were significantly associated with more favorable oncologic outcomes. Furthermore, specific gene mutations such as FGFR3 identified in ctDNA also demonstrated predictive value in UC patients. CONCLUSION: This meta-analysis demonstrates a strong association of ctDNA status and its dynamic change with survival outcomes in UC, suggesting substantial clinical utility of ctDNA testing in prognosis prediction and decision making in this setting.

Genome-wide association study and genomic prediction for resistance to brown planthopper in rice.

The brown planthopper (BPH) is the most destructive insect pest that threatens rice production globally. Developing rice varieties incorporating BPH-resistant genes has proven to be an effective control measure against BPH. In this study, we assessed the resistance of a core collection consisting of 502 rice germplasms by evaluating resistance scores, weight gain rates and honeydew excretions. A total of 117 rice varieties (23.31%) exhibited resistance to BPH. Genome-wide association studies (GWAS) were performed on both the entire panel of 502 rice varieties and its subspecies, and 6 loci were significantly associated with resistance scores (P value < 1.0e-8). Within these loci, we identified eight candidate genes encoding receptor-like protein kinase (RLK), nucleotide-binding and leucine-rich repeat (NB-LRR), or LRR proteins. Two loci had not been detected in previous study and were entirely novel. Furthermore, we evaluated the predictive ability of genomic selection for resistance to BPH. The results revealed that the highest prediction accuracy for BPH resistance reached 0.633. As expected, the prediction accuracy increased progressively with an increasing number of SNPs, and a total of 6.7K SNPs displayed comparable accuracy to 268K SNPs. Among various statistical models tested, the random forest model exhibited superior predictive accuracy. Moreover, increasing the size of training population improved prediction accuracy; however, there was no significant difference in prediction accuracy between a training population size of 737 and 1179. Additionally, when there existed close genetic relatedness between the training and validation populations, higher prediction accuracies were observed compared to scenarios when they were genetically distant. These findings provide valuable resistance candidate genes and germplasm resources and are crucial for the application of genomic selection for breeding durable BPH-resistant rice varieties.

Bioinformatics and Functional Analysis of OsASMT1 Gene in Response to Abiotic Stress.

The study aimed to elucidate the functional characteristics of OsASMT1 gene under copper (Cu) or sodium chloride (NaCl) stress. Bioinformatics scrutiny unveiled that OsASMT1 is situated on chromosome 9. Its protein architecture, comprising dimerization and methyltransferase domains, showed significant similarities to OsASMT2 and OsASMT3. High expression in roots and panicles, along with abiotic stress putative cis-regulatory elements in the promoter, indicated potential stress responsiveness. Real-time quantitative PCR confirmed OsASMT1 induction under Cu and NaCl stress in rice. Surprisingly, yeast expressing OsASMT1 did not exhibit enhanced resistance to abiotic stresses. The results of subcellular localization analysis indicated that OsASMT1 plays a role in the cytoplasm. While OsASMT1 responded to Cu and NaCl stress in rice, its heterologous expression in yeast failed to confer abiotic stress resistance, highlighting the need for further investigation of its functional implications.

Application value of intraoperative electrophysiological monitoring in cerebral eloquent area glioma surgery: a retrospective cohort study.

INTRODUCTION: Surgery for gliomas involving eloquent areas is a very challenging microsurgical procedure. Maximizing both the extent of resection (EOR) and preservation of neurological function have always been the focus of attention. Intraoperative neurophysiological monitoring (IONM) is widely used in this kind of surgery. The purpose of this study was to evaluate the efficacy of IONM in eloquent area glioma surgery. METHODS: Sixty-eight glioma patients who underwent surgical treatment from 2014 to 2019 were included in this retrospective cohort study, which focused on eloquent areas. Clinical indicators and IONM data were analysed preoperatively, two weeks after surgery, and at the final follow-up. Logistic regression, Cox regression, and Kaplan‒Meier analyses were performed, and nomograms were then established for predicting prognosis. The diagnostic value of the IONM indicator was evaluated by the receiver operating characteristic (ROC) curve. RESULTS: IONM had no effect on the postoperative outcomes, including EOR, intraoperative bleeding volume, duration of surgery, length of hospital stay, and neurological function status. However, at the three-month follow-up, the percentage of patients who had deteriorated function in the monitored group was significantly lower than that in the unmonitored group (23.3% vs. 52.6%; P < 0.05). Logistic regression analysis showed that IONM was a significant factor in long-term neurological function (OR = 0.23, 95% CI (0.07-0.70). In the survival analysis, long-term neurological deterioration indicated worsened overall survival (OS) and progression-free survival (PFS). A prognostic nomogram was established through Cox regression model analysis, which could predict the probability 3-year survival rate. The concordance index was 0.761 (95% CI 0.734-0.788). The sensitivity and specificity of IONM evoked potential (SSEP and TCeMEP) were 0.875 and 0.909, respectively. In the ROC curve analysis, the area under the curve (AUC) for the SSEP and TCeMEP curves was 0.892 (P < 0.05). CONCLUSIONS: The application of IONM could improve long-term neurological function, which is closely related to prognosis and can be used as an independent prognostic factor. IONM is practical and widely available for predicting postoperative functional deficits in patients with eloquent area glioma.

A new species of Populus and the extensive hybrid speciation arising from it on the Qinghai-Tibet Plateau.

While the diversity of species formation is broadly acknowledged, significant debate exists regarding the universal nature of hybrid species formation. Through an 18-year comprehensive study of all Populus species on the Qinghai-Tibet Plateau, 23 previously recorded species and 8 new species were identified. Based on morphological characteristics, these can be classified into three groups: species in section Leucoides, species with large leaves, and species with small leaves in section Tacamahaca. By conducting whole-genome re-sequencing of 150 genotypes from these 31 species, 2.28 million single nucleotide polymorphisms (SNPs) were identified. Phylogenetic analysis utilizing these SNPs not only revealed a highly intricate evolutionary network within the large-leaf species of section Tacamahaca but also confirmed that a new species, P. curviserrata, naturally hybridized with P. cathayana, P. szechuanica, and P. ciliata, resulting in 11 hybrid species. These findings indicate the widespread occurrence of hybrid species formation within this genus, with hybridization serving as a key evolutionary mechanism for Populus on the plateau. A novel hypothesis, "Hybrid Species Exterminating Their Ancestral Species (HSEAS)," is introduced to explain the mechanisms of hybrid species formation at three different scales: the entire plateau, the southeastern mountain region, and individual river valleys.

Compound Shenma Jingfu granule alleviates cerebral ischemia via HIF-1α-mediated promotion of angiogenesis.

BACKGROUND: Shenma Jingfu Granule, a traditional Chinese medicine formula, has been used clinically for the treatment of cerebral circulation insufficiency. However, the mechanism involved in alleviating cerebral ischemia has not yet been fully elucidated. METHODS: An integrated approach involving network pharmacology and transcriptomics was utilized to clarify the potential mechanisms of SMJF Granule. Molecular docking and surface plasmon resonance (SPR) were employed to identify potential targets and ingredients of SMJF Granule. The anti-CI effect of SMJF Granule was determined on the middle cerebral artery occlusion (MCAO) model by using hematoxylin-eosin (H&E) and Nissl's staining, as well as triphenyl tetrazolium chloride (TTC) staining, and the potential targets involved in the mechanisms were validated by RT-qPCR and western blotting. RESULTS: Integrated analysis revealed the mechanism of SMJF Granule intervening in CI injury might be related to the HIF-1 signaling pathway and angiogenesis. Molecular docking and SPR assays demonstrated robust binding interactions between key compounds like salvianolic acid A and naringenin with the core target HIF-1α protein. The experiment confirmed that SMJF Granule lowered neurological scores, diminished infarct volume, and alleviated histopathological changes in vivo. The possible mechanism of SMJF Granule was due to regulating HIF-1 pathway, which contributed to up-regulating expression of VEGF and vWF in the penumbral region, showing a significant promotion of angiogenesis. CONCLUSION: SMJF Granule promoted angiogenesis through HIF-1α pathway, thereby alleviating cerebral ischemia injury. In addition, our findings provide some evidence that SMJF Granule is a candidate compound for further investigation in treating CI in the clinical.

Atmospheric occurrences and bioavailability health risk of PAHs and their derivatives surrounding a non-ferrous metal smelting plant.

Non-ferrous metal smelting emits large amounts of organic compounds into the atmosphere. Herein, 20 parent polycyclic aromatic hydrocarbons (PPAHs), 9 nitrated PAHs (NPAHs), 14 chlorinated PAHs (ClPAHs), and 6 alkylated PAHs (APAHs) in atmospheric samples from a typical non-ferrous metal smelting plant (NMSP) and residential areas were detected. In NMSP, benzo[a]pyrene, dibenz[a,h]anthracene, 6-nitrochrysene, 9-chlorofluorene, and 1-methylfluorene were the predominant compounds in the particulate phase, while phenanthrene constituted 57.3% in the gaseous phase. The concentration of PAHs in residential areas around NMSP was 1.8 times higher than that in the control area. Additionally, there was a significant negative correlation between the concentration and the distance from the NMSP. In terms of health risks, although the skin penetration coefficient of PM2.5 is smaller than that of the gaseous phase, dermal absorption of PM2.5 posed a greater threat to the population, the incremental lifetime cancer risk (ILCR) of NMSP was 1.8 × 10-4. After considering bioavailability, BILCR decreased by 1-2 orders of magnitude in different regions, and dermal absorption decreased more than inhalation intake. Nevertheless, the dermal absorption of PM2.5 in NMSP still presents a probable carcinogenic risk. This study provides a necessary reference for the subsequent control of NMSP contamination.

A prospective randomized trial comparing the pocket-creation method and conventional method of endoscopic submucosal dissection in early gastric cancers and precancerous lesions.

BACKGROUND: Endoscopic submucosal dissection (ESD) is widely used as a standard treatment regimen for early gastric cancers (EGCs). However, such an approach is time-consuming and has a high risk of perforation and bleeding in some corner-site lesions because of the obscured view and difficulty in submucosal lifting. The newly developed pocket-creation method (PCM) provides a clearer view and better traction of the submucosal layer than conventional ESD (c-ESD). Nevertheless, no prospective randomized study has evaluated the efficacy of the PCM in EGCs and precancerous lesions. METHODS: This was a prospective randomized controlled trial. Patients with superficial gastric neoplastic lesions≥20mm were randomly assigned to the PCM-ESD group or c-ESD group. The primary outcome was dissection speed. RESULTS: There were 28 patients in the PCM-ESD group and 27 in the c-ESD group. The median dissection speed was significantly higher in the PCM-ESD group than in the c-ESD group (21.5 mm2/min vs. 14.3 mm2/min, P<0.001). Meanwhile, the operation time in the PCM-ESD group was significantly shorter than that in the c-ESD group (30min vs. 40min，P=0.047). In multiple linear regression analysis, the treatment method was independently associated with the resection speed of ESD. CONCLUSIONS: PCM-ESD was an effective and safe treatment for EGCs and precancerous lesions.