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Controlling the perovskite morphology and defects at the buried perovskite-substrate interface is challenging for inverted perovskite solar cells. In this work, we report an amphiphilic molecular hole transporter, (2-(4-(bis(4-methoxyphenyl)amino)phenyl)-1-cyanovinyl)phosphonic acid, that features a multifunctional cyanovinyl phosphonic acid group and forms a superwetting underlayer for perovskite deposition, which enables high-quality perovskite films with minimized defects at the buried interface. The resulting perovskite film has a photoluminescence quantum yield of 17% and a Shockley-Read-Hall lifetime of nearly 7 microseconds and achieved a certified power conversion efficiency (PCE) of 25.4% with an open-circuit voltage of 1.21 volts and a fill factor of 84.7%. In addition, 1–square centimeter cells and 10–square centimeter minimodules show PCEs of 23.4 and 22.0%, respectively. Encapsulated modules exhibited high stability under both operational and damp heat test conditions.

Parkinson’s disease (PD) is a neurodegenerative disorder that severely affects the motor system of patients. Early PD detection will greatly improve the quality of lives. However, existing automatic PD detection systems either rely on customized sensors or require users to perform special activities, using machine learning models whose prediction process is not understandable by medical professionals. In this article, we develop a non-disruptive PD detection system on smartphones based on interpretable prediction models. We design an application named PDGes to passively collect touchscreen and Inertial Measurement Unit data of users’ tapping and swiping actions on smartphones. Meaningful features that reflect finger dexterity , tremor , stiffness , and hand movement are extracted to build the prediction model. To better comprehend the decisions made by the model, we conduct a systematic analysis of feature importance to help validate the conformity of the model with clinical PD diagnosis. We collected data from 108 volunteers to evaluate the performance of PDGes . The experiment results show that PDGes achieves a detection accuracy of more than 94.5% on different smartphones.

Not Applicable.

Voice assistants (VA) have become prevalent on a wide range of personal devices such as smartphones and smart speakers. As companies build voice assistants with extra functionalities, attacks that trick a voice assistant into performing malicious behaviors can pose a significant threat to a user’s security, privacy, and even safety. However, the diverse attacks and stand-alone defenses in the literature often lack a systematic perspective, making it challenging for designers to properly identify, understand, and mitigate the security threats against voice assistants. To overcome this problem, this article provides a thorough survey of the attacks and countermeasures for voice assistants. We systematize a broad category of relevant but seemingly unrelated attacks by the vulnerable system components and attack methods, and categorize existing countermeasures based on the defensive strategies from a system designer’s perspective. To assist designers in planning defense based on their demands, we provide a qualitative comparison of existing countermeasures by the implementation cost, usability, and security and propose practical suggestions. We envision this work can help build more reliability into voice assistants and promote research in this fast-evolving area.

RNA-binding protein (RBP) dysregulation is functionally linked to several human diseases, including neurological disorders, cardiovascular disease, and cancer. Heterogeneous nuclear ribonucleoproteins (hnRNPs) are a diverse family of RBPs involved in nucleic acid metabolism. A growing body of studies has shown that the dysregulated hnRNPs play important roles in tumorigenesis. Here, we found that heterogeneous nuclear ribonucleoprotein C (C1/C2) (HNRNPC) had good performance in distinguishing between hepatocellular carcinoma (HCC) and normal liver tissues through bioinformatics analysis. Further investigation revealed that HNRNPC was significantly correlated with multiple malignant characteristics of HCC, including tumor size, microvascular invasion, tumor differentiation, and TNM stage. Patients with HCC with positive HNRNPC expression exhibited decreased overall survival and increased recurrence rate. HNRNPC downregulation inhibited HCC invasion and metastasis. The decreased expression of hypoxia inducible factor 1 subunit alpha (HIF1A) was identified as the molecular mechanism underlying HNRNPC downregulation-inhibited HCC metastasis by RNA sequencing. Mechanistically, HNRNPC downregulation decreased HIF1A expression by destabilizing HIF1A mRNA. HIF1A overexpression rescued the decrease in invasiveness and metastasis of HCC induced by HNRNPC downregulation. Additionally, interleukin (IL)-6/STAT3 signaling upregulated HNRNPC expression in HCC cells, and knockdown of HNRNPC significantly inhibited IL-6/STAT3-enhanced HCC metastasis. Furthermore, anti-IL-6 antibody siltuximab significantly inhibited IL-6-mediated HCC metastasis. In summary, our research revealed the clinical value, functional role, and molecular mechanism of HNRNPC in HCC and showed the potential of HNRNPC as a biomarker for diagnosis, prognosis, and further therapeutic targets for HCC.

A classification system for endocervical adenocarcinoma (ECA) based on high-risk human papillomavirus (HPV) status has been established; however, the immunohistochemical markers distinguishing HPV-independent and HPV-associated ECAs have not been fully described. Here, we aimed to characterize ECA immunopathological features.We evaluated the immunohistochemical profile of CLDN18, CDX2, PAX8, p16, p53, and CEA in 60 ECAs comprising 10 HPV-independent ECAs and 50 HPV-associated ECAs. Both the membranous and nuclear expression levels of CLDN18 were analyzed.Membranous CLDN18 (CLDN18 [M]) was found to be expressed in the mucinous epithelium of all HPV-independent ECAs, including eight gastric-type ECAs (G-ECAs), one endometrioid ECA, and one clear cell ECA, but no nuclear CLDN18 (CLDN18 [N]) expression was detected in HPV-independent ECAs. Among HPV-associated ECAs, CLDN18 (M) expression levels in intestinal-type (I-ECAs) and usual-type ECAs (U-ECAs) were significantly different from those in invasive stratified mucin-producing (iSMILE) carcinomas (p = 0.036). Positive CLDN18 (M) staining was present in 55.6% (5/9) of intestinal-type and 39.4% (13/33) of usual-type ECAs and was not present in iSMILE ECAs. Silva pattern C cancers expressed higher levels of CLDN18 (M) than Silva pattern A and B cancers (p = 0.004), whereas the CLDN18 (N) expression levels in cancers showing Silva pattern A were significantly higher than those in cancers exhibiting Silva patterns B and C (p 0.001).Membranous CLDN18 is expressed in ECAs and is particularly frequently expressed in HPV-independent ECAs, and membranous CLDN18 expression has potential as a therapeutic target. Nuclear staining of CLDN18 is a new immunohistochemical marker for diagnosing Silva pattern A HPV-associated ECAs and is associated with a good prognosis. Further studies should investigate the therapeutic and prognostic significance of membranous and nuclear CLDN18 expression and develop a related test that can be implemented in the clinical evaluation of ECAs.

Herb-induced liver injury results from the interplay between the herb and host with the herbal components serving as the major origin for hepatotoxicity. Although Polygoni Multiflori Radix (PMR) has been frequently reported to induce liver injury, contributions of its major components such as emodin, emodin-8-O-β-D-glucopyranoside, physcion and 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucopyranoside (TSG) towards its hepatotoxicity have not been clearly identified. Our initial cytotoxicity screenings of the major PMR components using rat hepatocytes identified emodin as the most toxic. Subsequently, the bile acid homeostasis-related mechanisms of emodin and its combination treatment with TSG in PMR-associated liver injury were explored in sandwich-cultured rat hepatocytes (SCRH) and verified in rats. In SCRH, emodin was found to be able to induce total bile acid accumulation in a dose-dependent manner. In both SCRH and rats, the presence of TSG significantly enhanced the hepatotoxicity of emodin via i) increasing its hepatic exposure by inhibiting its glucuronidation mediated metabolism; ii) enhancing its disruption on bile acid homeostasis through amplifying its inhibition on bile acid efflux transporters and its up-regulation on bile acids synthesis enzymes; iii) enhancing its apoptosis. Our study for the first time demonstrated the critical role of the combination treatment with emodin and TSG in PMR-induced liver injury.

Alzheimer's disease (ad), the leading cause of dementia, is characterized by the accumulation of beta-amyloid peptides (Aβ). However, whether Aβ itself is a key toxic agent in ad pathogenesis and the precise mechanism of Aβ-elicited neurotoxicity are still debated. Emerging evidence demonstrates that the Aβ channel/pore hypothesis could explain Aβ toxicity, because Aβ oligomers are able to disrupt membranes and cause edge-conductivity pores that may disrupt cell Ca2+ homeostasis and drive neurotoxicity in ad. However, all available data to support this hypothesis have been collected from “in vitro” experiments using high concentrations of exogenous Aβ. It is still unknown whether Aβ channels can be formed by endogenous Aβ in ad animal models. Here we report an unexpected finding of the spontaneous Ca2+ oscillations in aged 3XTg ad mice but not in age-matched wild-type (WT) mice. These spontaneous Ca2+ oscillations are sensitive to extracellular Ca2+, ZnCl2, and the Aβ channel blocker Anle138b, suggesting that these spontaneous Ca2+ oscillations in aged 3XTg ad mice are mediated by endogenous Aβ-formed channels.

The spontaneous formation of self-assembly monolayer (SAM) on various substrates represents an effective strategy for interfacial engineering of optoelectronic devices. Hole-selective SAM is becoming popular among high-performance inverted perovskite solar cells (PSCs), but the presence of strong acidic anchors (such as -PO3H2) in state-of-the-art SAM is detrimental to device stability. Herein, we report for the first time that acidity-weakened boric acid can function as an alternative anchor to construct efficient SAM-based hole-selective contact (HSC) for PSCs. Theoretical calculations reveal that boric acid spontaneously chemisorbs onto indium tin oxide (ITO) surface with oxygen vacancies facilitating the adsorption progress. Spectroscopy and electrical measurements indicate that boric acid anchor significantly mitigates ITO corrosion. The excess boric acid containing molecules improves perovskite deposition and results in a coherent and well-passivated bottom interface, which boosts the fill factor (FF) performance for a variety of perovskite compositions. The optimal boric acid anchoring HSC (MTPA-BA) can achieve power conversion efficiency close to 23% with a high FF of 85.2%. More importantly, the devices show improved stability: 90% of their initial efficiency is retained after 2400 h storage (ISOS-D-1) or 400 h operation (ISOS-L-1), which are 5-fold higher than those of phosphoric acid SAM based devices. Acidity-weakened boric acid SAM, which are friendly to ITO, well exhibits great potential to improve stability of interface as well as device.

Solid-state batteries have become a frontrunner in humankind’s pursuit of safe and stable energy storage systems with high energy and power density. Electrolyte materials, currently, seem to be the Achilles’ heel of solid-state batteries due to the slow kinetics and poor interfacial wetting. Combining the merits of solid inorganic electrolytes (SIEs) and solid polymer electrolytes (SPEs), inorganic/polymer hybrid electrolytes (IPHEs) integrate improved ionic conductivity, great interfacial compatibility, wide electrochemical stability window, and high mechanical toughness and flexibility in one material, having become a sought-after pathway to high-performance all-solid-state lithium batteries. Herein, we present a comprehensive overview of recent progress in IPHEs, including the awareness of ion migration fundamentals, advanced architectural design for better electrochemical performance, and a perspective on unconquered challenges and potential research directions. This review is expected to provide a guidance for designing IPHEs for next-generation lithium batteries, with special emphasis on developing high-voltage-tolerance polymer electrolytes to enable higher energy density and three-dimensional (3D) continuous ion transport highways to achieve faster charging and discharging.

Endoscopic resection (ER) gradually becomes an important treatment method for gastrointestinal stromal tumors (GISTs). The aim of this study is to evaluate the efficacy and safety of ER of gastric GISTs.This retrospective study included 240 patients with gastric GISTs who underwent ER at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2010 to December 2019. The clinicopathologic, endoscopic and follow-up data of the patients were collected and analyzed.The mean maximum tumor diameter was 1.67 ± 1.00 cm (range 0.2-6.5 cm), of which 156 cases (65.00%) were small gastric GISTs (tumor diameter2 cm). A total of 43 patients (17.92%) had perioperative bleeding, including 40 cases (16.67%) of minor bleeding and three cases (1.25%) of major bleeding. Perioperative perforation occurred in 101 patients (42.08%), of which 51 patients (21.25%) were active perforation and 50 patients (20.83%) were passive perforation. The en bloc resection rate was 97.08% (233/240), and seven cases (2.92%) had piecemeal resection. There were three cases (1.92%) of small gastric GISTs at intermediate risk and one case (0.64%) at high risk. A total of 193 patients were followed up, and no tumor residual, recurrence or metastasis occurred within a median follow-up time of 30 months (range 1-127 months).Endoscopic treatment for gastric GISTs is safe and effective. Piecemeal resection does not seem to be related to the patient's prognosis. Endoscopic resection can be performed if patients are willing to remove small gastric GISTs.

Many large benign thyroid nodules have symptoms and cosmetic problems. This study consisted of a meta-analysis to accurately assess the effect of thermal ablation on these nodules.The PubMed, Embase, Web of Science, and Scopus databases were systematically searched for retrospective or prospective studies of thermal ablation since June 1, 2021. The weighted mean differences of the measures were analysed before and after treatment.A total of 10 eligible studies were included. By comparing the initial nodule volume with the nodular volume after thermal ablation, we found that the volume reduction rate was increased significantly after 1 month (SMD = 0.453, 95% CI: 0.323-0.583, p lt; .001), 3 months (SMD = 0.655, 95% CI: 0.563-0.747, p lt; .001), 6 months (SMD = 0.691, 95% CI: 0.607-0.774, p lt; .001), and 12 months (SMD = 0.694, 95% CI: 0.583-0.803), p lt; .001). The nodular volume was also found to decrease significantly, after 1 month (SMD = 2.381, 95% CI: 1.278-3.485, p lt; .001), 3 months (SMD = 5.071, 95% CI: 2.386-7.756, p lt; .001), 6 months (SMD = 5.363, 95% CI: 2.765-7.962, p lt; .001), and 12 months (SMD = 8.194, 95% CI: 2.113-14.274), p lt; .001). Symptom score (SMD = 4.419, 95% CI: 2.573-6.265, p lt; .001)and cosmetic score (SMD = 4.245, 95% CI: 2.566-5.359, p lt; .001) were reduced after thermal ablation.Thermal ablation could become an alternative to manage large benign thyroid nodules.

Wumei San (WMS) is a traditional Chinese medicine that has been widely applied in the treatment of piglet diarrhea (PD). However, the mechanism of WMS in PD has not been investigated. In this study, the main active compounds of WMS and the target proteins were obtained from the Traditional Chinese Medicine Systematic Pharmacology, PubChem, and SwissTargetPrediction databases. The molecular targets of PD were identified using GeneCards, OMIM, and NCBI databases. The common targets of WMS and PD were screened out and converted into UniProt gene symbols. PD-related target genes were constructed into a protein-protein interaction network, which was further analyzed by the STRING online database. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to construct the component-target gene-disease network. Molecular docking was then used to examine the relationship between the core compounds and proteins. As a result, a total of 32 active compounds and 638 target genes of WMS were identified, and a WMS-compound-target network was successfully constructed. Through network pharmacology analysis, 14 core compounds in WMS that showed an effect on PD were identified. The targets revealed by GO and KEGG enrichment analysis were associated with the AGE-RAGE signaling pathway, PI3K-Akt signaling pathway, TNF signaling pathway, NOD-like receptor signaling pathway, IL-17 signaling pathway, and other pathways and physiological processes. Molecular docking analysis revealed that the active compounds in WMS spontaneously bind to their targets. The results indicated that WMS may regulate the local immune response and inflammatory factors mainly through the TNF signaling pathway, IL-17 signaling pathway, and other pathways. WMS is a promising treatment strategy for PD. This study provides new insights into the potential mechanism of WMS in PD.

PurposeTo analyze and predict the possibility of visual field (VF) recovery after endoscopic transsphenoidal surgery (ETSS) in patients with pituitary adenoma, we investigated the factors affecting the improvement of the visual field defect (VFD) and built a nomogram predictive model based on these risk factors. We further investigated specific recovery regions of VF associated with the improvement of VFD.MethodsThe clinical data of patients who underwent ETSS for pituitary adenomas at a single center between the January 2021 and April 2022 were retrospectively analyzed. Univariate and multivariate analyses were used to determine the predictive factors affecting the improvement in the VF defect and specific recovery regions in patients with pituitary adenomas after ETSS.ResultsWe enrolled 28 patients (56 eyes) who were hospitalized at our institution. Four clinical features, including compression of the optic chiasm, preoperative mean defect (MD), diffuse defect, and duration of the visual symptom, were chosen from the least absolute shrinkage and selection operator regression analysis to establish the predictive nomogram. The nomogram’s area under the curve (AUC) was 0.912, indicating a good degree of differentiation. A calibration plot was used to evaluate the predictive model’s calibration, and a decision curve was used to evaluate its clinical application value. The VF defects were improved in the 270–300° range (270–300: RR = 361.00, 95% CI: 21.01–6,202.41).ConclusionWe developed a predictive nomogram model based on significant visual field improvement-associated factors after ETSS in patients with pituitary adenoma. Postoperative visual field improvement is likely to begin at 270–300° in the inferior temporal quadrant. This improvement would enable personalized counselling for individual patients by precisely predicting the visual field recovery after surgery.

Background: Cuproptosis is a newly defined form of cell death, whether cuproptosis involved in hepatocellular carcinoma (HCC) remains elusive.Method: We obtained patients’ RNA expression data and follow-up information from University of California Santa Cruz (UCSC) and The Cancer Genome Atlas (TCGA). We analyzed the mRNA level of Cuproptosis-related genes (CRGs) and performed univariate Cox analysis. Liver hepatocellular carcinoma (LIHC) was chosen for further investigation. Real-Time quantitative PCR (RT-qPCR), Western blotting (WB), Immunohistochemical (IHC), and Transwell assays were used to determine expression patterns and functions of CRGs in LIHC. Next, we identified CRGs-related lncRNAs (CRLs) and differentially expressed CRLs between HCC and normal cases. Univariate Cox analysis, least absolute shrinkage selection operator (LASSO) analysis and Cox regression analysis were used to construct the prognostic model. Univariate and multivariate Cox analysis was used to assess whether the risk model can act as an independent risk factor of overall survival duration. Different risk groups performed immune correlation analysis, tumor mutation burden (TMB), and Gene Set Enrichment Analysis (GSEA) analysis were performed in different risk groups. Finally, we assessed the performance of the predictive model in drug sensitivity.Results: CRGs expression levels have significant differences between tumor and normal tissues. High expression of Dihydrolipoamide S-Acetyltransferase (DLAT) correlated to metastasis of HCC cells and indicated poor prognosis for HCC patients. Our prognostic model consisted of four cuproptosis-related lncRNA (AC011476.3, AC026412.3, NRAV, MKLN1-AS). The prognostic model performed well in predicting survival rates. The results from Cox regression analysis suggested that risk score can serve as an independent prognostic element for survival durations. Survival analysis revealed that low risk patients have extended survival periods compared with those with high risk. The results of the immune analysis indicated that risk score has a positive correlation with B cell and CD4+ T cell Th2, while has a negative relationship with endothelial cell and hematopoietic cells. Besides, immune checkpoint genes have higher expression folds in the high-risk set than in the low-risk set. The high-risk group had higher rates of genetic mutation than the low-risk set while having a shorter survival time. GSEA revealed the signaling pathways enriched in the high-risk group were mostly immune-related, while metabolic-related pathways were enriched in the low-risk group. Drugs sensitivity analysis indicated that our model has the ability to predict the efficacy of clinical treatment.Conclusion: The Cuproptosis-related lncRNAs prognostic formula is a novel predictor of HCC patients’ prognosis and drug sensitivity.

With the widespread use of smart devices, device authentication has received much attention. One popular method for device authentication is to utilize internally measured device fingerprints, such as device ID, software or hardware-based characteristics. In this article, we propose DeMiCPU , a stimulation-response-based device fingerprinting technique that relies on externally measured information, i.e., magnetic induction (MI) signals emitted from the CPU module that consists of the CPU chip and its affiliated power-supply circuits. The key insight of DeMiCPU is that hardware discrepancies essentially exist among CPU modules and thus the corresponding MI signals make promising device fingerprints, which are difficult to be modified or mimicked. We design a stimulation and a discrepancy extraction scheme and evaluate them with 90 mobile devices, including 70 laptops (among which 30 are of totally identical CPU and operating system) and 20 smartphones. The results show that DeMiCPU can achieve 99.7% precision and recall on average, and 99.8% precision and recall for the 30 identical devices, with a fingerprinting time of 0.6~s. The performance can be further improved to 99.9% with multi-round fingerprinting. In addition, we implement a prototype of DeMiCPU docker, which can effectively reduce the requirement of test points and enlarge the fingerprinting area.

In this work, the monomer N, N′-bis(4-fluorobenzamide)dicyclohexyl methane (BFDCM) was synthesized successfully by 4-fluorobenzoylchloride and 4,4′-diaminodicyclohexylmethane through interfacial reaction, and then the monomer BFDCM and 1,4-benzenediol (HQ) or 4.4′-biphenol (BH) were used to prepare the novel poly(arylene ether amide) (HQ-BFDCM and BH-BFDCM) containing an aliphatic ring in the main chain by nucleophilic substitution in NMP solution. These two polymers exhibited the inherent viscosities ranging from 0.828 to 1.044 dL g−1, high glass-transition temperatures (Tg) of 214.1–235.0 °C, and weight-loss temperature (T5%) of 425.2–441.3 °C. The polymers HQ-BFDCM and BH-BFDCM could completely or partly dissolve in some polar solutions, such as NMP, DMF, and so on, and they showed moderate corrosion resistance. Additionally, the obtained polymers HQ-BFDCM and BH-BFDCM exhibited good optical property, and the optical transmittances of HQ-BFDCM and BH-BFDCM were 74% and 80% at 450 nm, respectively, which showed that they could be applied to the heat-resistant optical films.

The application of Si as the anode materials for lithium-ion batteries (LIBs) is still severely hindered by the rapid capacity decay due to the structural damage caused by large volume change (>300%) during cycling. Herein, a three-dimensional (3D) aerogel anode of Si@carbon@graphene (SCG) is rationally constructed via a polydopamine-assisted strategy. Polydopamine is coated on Si nanoparticles to serve as an interface linker to initiate the assembly of Si and graphene oxide, which plays a crucial role in the successful fabrication of SCG aerogels. After annealing the polydopamine is converted into N-doped carbon (N-carbon) coatings to protect Si materials. The dual protection from N-carbon and graphene aerogels synergistically improves the structural stability and electronic conductivity of Si, thereby leading to the significantly improved lithium storage properties. Electrochemical tests show that the SCG with optimized graphene content delivers a high capacity (712 mAh/g at 100 mA/g) and robust cycling stability (402 mAh/g at 1 A/g after 1500 cycles). Furthermore, the full cell using SCG aerogels as anode exhibits a reversible capacity of 187.6 mAh/g after 80 cycles at 0.1 A/g. This work provides a plausible strategy for developing Si anode in LIBs.

Arabidopsis (Arabidopsis thaliana) UNFERTILIZED EMBRYO SAC 12 (AtUNE12) belongs to the basic helix–loop–helix DNA-binding superfamily of proteins. However, its function is not well known. Here, we found that AtUNE12 plays an important role in mediating salt tolerance. AtUNE12 is a transcriptional activator located in the nucleus whose expression is induced by NaCl, mannitol, and abscisic acid. In addition to binding to the G-box “CACGTG”, AtUNE12 also binds to the low temperature responsive element 15 (LTRE15) “CCGAC”. Furthermore, the serine residue at position 108 of AtUNE12 is phosphorylated during the salt stress response, enabling AtUNE12 to trigger gene expression by binding to G-box and/or LTRE15 motifs. Phosphorylated AtUNE12 regulates the expression of the genes involved in ion transport leading to reduced Na+ accumulation and K+ loss. At the same time, phosphorylation of AtUNE12 also induces the expression of AtMYB61 to decrease stomatal aperture, leading to a reduced transpiration rate. Overall, AtUNE12 serves as a transcriptional activator that is induced and phosphorylated upon salt stress, and the induction and phosphorylation of AtUNE12 in turn activate the salt-overly-sensitive pathway and decrease the stomatal aperture, enabling improved salt tolerance.

Alzheimer disease (AD) is the most common neurodegenerative disease of the central nervous system. The stability of the telomere-telomerase system is closely related to AD. A previous meta-analysis indicated that AD patients had shorter telomere length (TL) than control subjects. However, there are no consistent telomerase activity findings in AD patients, and the published telomerase studies were not meta-analyzed yet.We searched all the related studies that probed into TL and/or telomerase activity in AD patients based on PubMed and Embase database from the establishment to September 2020. The Chinese National Knowledge Infrastructure, Wanfang and China Science and Technology Journal Database were also utilized. The quality of the included studies was evaluated by using Newcastle-Ottawa Scale. All the statistical analyses of this meta-analysis were performed using Stata version 15.0.Analyzing 30 TL data from 2248 AD patients and 4865 controls, AD patients had a significantly shorter TL than the controls, with a standardized mean difference of -0.70 (confidence interval: -0.95 to -0.46; P0.05). The meta-analysis included 3 primary studies and did not find a significant difference in the telomerase activity between 233 AD patients and 132 controls, but AD patients had a trend of increased telomerase activity compared with controls (standardized mean difference: 0.47; confidence interval: -0.29 to 1.23; P0.05).Our results showed that compared with the control group, the AD group had a shorter TL and may have higher telomerase activity.

Although Polygoni Multiflori Radix (PMR) has been widely used as a tonic and an anti-aging remedy for centuries, the extensively reported hepatotoxicity and potential kidney toxicity hindered its safe use in clinical practice. To better understand its toxicokinetics, the current study was proposed, aiming to evaluate the biodistributions of the major PMR components including 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucopyranoside (TSG), emodin, emodin-8-O-β-D-glucopyranoside (EMG) and physcion as well as their corresponding glucuronides following bolus and multiple oral administrations of PMR to rats. Male Sprague-Dawley rats received a bolus dose or 21 days of oral administrations of PMR concentrated granules at 4.12 g/kg (equivalent to 20.6 g/kg raw material). Fifteen minutes after bolus dose or the last dose on day 21, rats were sacrificed and the blood, liver, and kidney were collected for the concentration determination of both parent form and glucuronides of TSG, emodin, EMG, and physcion by HPLC-MS/MS. Among all the tested analytes, TSG, EMG, EMG glucuronides in liver and TSG, EMG, as well as all the glucuronides of these analytes in the kidney demonstrated the most significant accumulation after multiple doses. Moreover, the levels of the parent analytes were all significantly higher in liver and kidney in comparison to their plasma levels. Strong tissue binding of all four analytes and accumulation of TSG, EMG, and EMG glucuronides in the liver and TSG, EMG, as well as the glucuronides of all four analytes in the kidney after multiple dosing of PMR were considered to be associated with its toxicity.

Background and Purpose: Berberine, a natural isoquinoline alkaloid, exhibits a variety of pharmacological effects but the pharmacological targets and mechanisms are remained elusive. Here, we report a novel finding that berberine inhibits acetylcholine (ACh)-induced Ca2+ oscillations which may underlie the pathogenesis of the L-arginine-induced mouse model of acute pancreatitis (AP). Experimental approach: Patch-clamp recordings and confocal Ca2+ imaging were applied in acute dissociated pancreatic acinar cells prepared from CD1 mice to examine the effects of berberine on ACh-induced Ca2+ oscillations. The L-arginine-induced acute pancreatitis mouse model was used to evaluate the protective effects of berberine against pathological changes. Key Results: Whole-cell patch-clamp recordings showed that berberine (from 0.1 to 10 µM) reduced ACh-induced Ca2+ oscillations in a concentration-dependent manner, and this inhibition was also depended on ACh concentrations. The inhibitory effect of berberine neither occurred in intracellular targets nor extracellular cholecystokinin (CCK) receptors, chloride (Cl-) channels, and store-operated Ca2+ channels. Together, the results demonstrate that berberine directly inhibits M3 muscarinic receptors, which is further confirmed by the evidence of the interaction between berberine and M3 receptors in acinar cells. In a L-arginine AP model, berberine eliminates the ACh-induced Ca2+ oscillations, the elevation of pancreatic amylase and pulmonary myeloperoxidase, and improves acinar cell pathological injury. Conclusions and Implications: We provide novel evidence that berberine inhibits M3 receptors, in turn eliminates ACh-induced Ca2+ oscillations and L-arginine-enhanced Ca2+ signaling, which underlie the protective effects of berberine on pancreatic acinar cells against pathological changes in an acute pancreatitis model.

The GRAS gene family is a plant-specific family of transcription factors and play a vital role in many plant growth processes and abiotic stress responses. Nevertheless, the functions of the GRAS gene family in woody plants, especially in Betula platyphylla (birch), are hardly known. In this study, we performed a genome-wide analysis of 40 BpGRAS genes (BpGRASs) and identified typical GRAS domains of most BpGRASs. The BpGRASs were unevenly distributed on 14 chromosomes of birch and the phylogenetic analysis of six species facilitated the clustering of 265 GRAS proteins into 17 subfamilies. We observed that closely related GRAS homologs had similar conserved motifs according to motif analysis. Besides, an analysis of the expression patterns of 26 BpGRASs showed that most BpGRASs were highly expressed in the leaves and responded to salt stress. Six BpGRASs were selected for cis-acting element analysis because of their significant upregulation under salt treatment, indicating that many elements were involved in the response to abiotic stress. This result further confirmed that these BpGRASs might participate in response to abiotic stress. Transiently transfected birch plants with transiently overexpressed 6 BpGRASs and RNAi-silenced 6 BpGRASs were generated for gain- and loss-of-function analysis, respectively. In addition, overexpression of BpGRAS34 showed phenotype resistant to salt stress, decreased the cell death and enhanced the reactive oxygen species (ROS) scavenging capabilities and proline content under salt treatment, consistent with the results in transiently transformed birch plants. This study is a systematic analysis of the GRAS gene family in birch plants, and the results provide insight into the molecular mechanism of the GRAS gene family responding to abiotic stress in birch plants.

In the past few decades, acromegaly and colonic polyps have been associated with an increased risk of colorectal cancer. Previous studies highlighted the importance of serum biomarkers of colonic polyps in patients with acromegaly.We reviewed studies on serum biomarkers of colonic polyps in patients with acromegaly, published on PubMed, Embase, Cochrane Library, Medline, and Chinese databases from January 1, 1966, to May 8, 2022. Meta-analysis and systematic review were conducted using Stata MP 14.0.Eight articles were included in this study. The mean (standard deviation) concentrations of serum biomarkers for acromegaly with and without colorectal polyps were extracted from these studies. Meta-analysis results showed that, compared to patients without colonic polyps, the levels of insulin-like growth factor-1 × upper limit of normal range (IGF-1 × ULN) and fasting insulin were significantly increased; while the levels of growth hormone (GH) were significantly decreased in patients with acromegaly and colonic polyps (IGF-1 × ULN: SMD 0.23; 95% CI 0.03-0.42, p 0.05) (fasting insulin: SMD 0.95; 9 5% CI 0.11-1.8, p 0.05) (GH: SMD - 0.25; 95% CI - 0.41 to - 0.08, p 0.05). IGF-1 and FPG levels did not differ significantly (IGF-1: SMD -0.03; 95% CI - 0.22 to 0.17, p 0.05) (FPG: SMD 0.14; 95% CI - 0.23 to 0.52, p 0.05). The systematic review results suggest no significant differences in hemoglobin A1C, TSH, free thyroxine, FT4, T3, PRL, total cholesterol, HDL, LDL, fibrinogen, clathrate antigen, serum antigen 19-9, and α-fetoprotein levels, but serum Klotho levels.We present the first meta-analysis and systematic review of serum biomarkers in patients with acromegaly or colonic polyps. The prevalence of colonic lesion polyps, is associated with higher IGF-1 × ULN levels, higher insulin levels in acromegaly. Further research is required to confirm GH and serum soluble Klotho levels as biomarkers of colonic polyps. When IGF-1 × ULN, fasting insulin levels change in patients with acromegaly, the occurrence of colonic polyps should be monitored. Early detection may reduce the possibility of developing malignant colon neoplasms.

Papillary thyroid microcarcinoma (PTMC) comprises more than 50% of all newly detected cases of papillary thyroid carcinoma (PTC). High-volume lymph node metastasis (involving5 lymph nodes) (hv-LNM) is associated with PTMC recurrence. In half of the clinically node-negative (cN0) PTMC patients, central lymph node metastasis (CLNM) is pathologically present. However, clinical risk factors for high-volume CLNM (hv-CLNM) in cN0 PTMC have not been defined well. Therefore, we aimed to obtain evidence for hv-CLNM risk factors in cN0 PTMC.Data on patients who visited our hospital between January 2020 and December 2021 were collected; a preoperative diagnosis of cN0 and a postoperative pathological confirmation of PTMC were obtained. After filtering by inclusion versus exclusion criteria, the obtained data (N = 2268) were included in the meta-analysis. Relevant studies published as of 10 April 2022, were identified from the Web of Science, PubMed, WANFANG, and CNKI databases. These eligible studies were included in the meta-analysis and the association between clinicopathological factors and hv-CLNM in cN0 PTMC was assessed. SPSS and MetaXL were used for statistical analyses.The meta-analysis included 10 previous studies (11,734 patients) and 2268 patients enroled in our hospital for a total of 14,002 subjects. The results of which suggested that younger age (40, odds ratio [OR] = 3.28, 95% confidence interval [CI] = 2.75-3.92, p .001 or45 odds ratio [OR] = 2.93, 95% CI = 2.31-3.72, p .001), male sex (OR = 2.81, 95% CI = 2.25-3.52, p .001), tumour size5 mm (OR = 1.85, 95% CI = 1.39-2.47, p .001), multifocality (OR = 1.88, 95% CI = 1.56-2.26, p .001), extrathyroidal extension (OR = 2.58, 95% CI = 2.02-3.30, p .001), capsule invasion (OR = 2.02, 95% CI = 1.46-2.78, p .001), microcalcification (OR = 3.25, 95% CI = 2.42-4.36, p .001) and rich blood flow (OR = 1.65, 95% CI = 1.21-2.25, p = .002) were the significant factors related to an elevated hv-CLNM risk in cN0 PTMC patients. Hashimoto thyroiditis (OR = 0.76, 95% CI = 0.55-1.07, p = .114), irregular margin (versus regular margin, OR = 0.96, 95% CI = 0.68-1.33, p = .787) and hypoechoic (versus nonhypoechoic, OR = 1.27, 95% CI = 0.84-1.92, p = .261) showed no significant association with hv-CLNM.Younger age, tumour size5 mm, males, extrathyroidal extension, multifocality, microcalcification, capsular invasion, and rich blood flow were the significant clinicopathological risk factors for hv-CLNM risk in cN0 PTMC patients. These predictors may compensate for the sensitivity of imaging diagnosis in the preoperative period, thus helping in the effective identification of PTMCs with an invasive phenotype.