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Background: The current lack of effective drug therapies for Alzheimer’s disease (AD) has prompted researchers to seek alternative nutritional therapies, such as medium chain triglycerides (MCTs). However, results are inconclusive. Objective: This systematic review and meta-analysis aims to summarize current evidence on the effect of MCT on cognitive function in patients with mild cognitive impairment (MCI) or AD. Methods: A systematic search was conducted up until December 16, 2022, to identify human interventions reporting the effects of MCT on cognitive functioning of MCI or AD patients. 995 non-duplicated publications were identified, of which nine (n = 10 studies) met the inclusion criteria. Results: Meta-analysis showed cognitive improvements in general (SMD = 0.64; 95% CI [0.05, 1.24]), but not in memory, language, and attention domains after oral MCT administration, compared to placebo. The effect of MCT was greater among APOE ɛ4 (−) subjects than APOE ɛ4 (+) subjects (SMD = 1.87; 95% CI [0.35, 3.40]). Conclusion: This review provides some evidence that treatment with MCT could improve general cognitive function in APOE ɛ4 (−) cognitive impaired patients. Better characterized clinical studies are warranted before making a definitive conclusion on the use of MCT for MCI and AD management.

The inorganic elements have unique properties in biochemical processes in humans. An increasing number of pathologies have been associated with essential element ions, such as lead, mercury, and cadmium. Hair has become an attractive clinical specimen for studying the longitudinal exposure to elements from the external environment. Inductively coupled plasma-mass spectrometry (ICP-MS) coupled with nitric acid (HNO3) digestion is the most common approach for determining inorganic elements from human hair. This study aims to optimize the digestion method for the absolute quantitation of 52 elements using ICP-MS, for a large cohort study in human hair. Five different HNO3 (65%) digestion methods were investigated and evaluated for their internal standard solution stability, reproducibility, element coverage, and standard solution recovery efficiency, namely, room temperature for 24 h (RT), 90°C for 4 h (T90), ultrasonic-assisted digestion (UltraS), programmed digestion of microwave digestion (MicroD), and ordinary microwave oven digestion (O-MicroD). Our results demonstrated that O-MicroD, MicroD, and RT were the best performing digestion methods for coefficient of variation (CV) scores, coverage, and recovery efficiency, respectively. In particular, the O-MicroD method detected multiple elements in a small quantity of hair (3 mg), with minimum nitric acid usage (200 μl) and a short digestion time (30 min). The O-MicroD method had excellent reproducibility, as demonstrated by a continuous thousand injections of hair samples with three internal standards (CV: 103Rh = 3.59%, 115In = 3.61%, and 209Bi = 6.31%). Future studies of the elemental content of hair should carefully select their digestion method to meet the primary purpose of their study.

Chronic kidney disease (CKD) is a major health problem. Kidney fibrosis is a hallmark and final common pathway of CKD. The Hippo/YAP pathway regulates organ size, inflammation and tumorigenesis. Our previous study demonstrated that tubular YAP activation by tubule-specific double knockout (dKO) of Mst1/2 induced CKD in mice, but the underlying mechanisms remain to be fully elucidated. AP-1 activation was found to promote tubular atrophy and tubulointerstitial fibrosis. Therefore, we studied whether YAP regulates AP-1 expression in the kidney. We found that expression of various AP-1 components was induced in kidneys subjected to unilateral ureteric obstruction (UUO) and in Mst1/2 dKO kidneys, and these inductions were blocked by deletion of Yap in tubular cells, with Fosl1 being most affected compared with other AP-1 genes. Inhibition of Yap also most highly suppressed Fosl1 expression among AP-1 genes in HK-2 and IMCD3 renal tubular cells. YAP bound to the Fosl1 promotor and promoted Fosl1 promoter luciferase activity. Our results suggest that YAP controls AP-1 expression, and that Fosl1 is the primary target of YAP in renal tubular cells.

Vortices are topological defects associated with superfluids and superconductors, which, when mobile, dissipate energy destroying the dissipation-less nature of the superfluid. The nature of this "quantum dissipation" is rooted in the quantum physical nature of the problem, which has been subject of an extensive literature. However, this has mostly be focused on the measures applicable in weakly interacting systems wherein they are tractable via conventional methods. Recently it became possible to address such dynamical quantum thermalization problems in very strongly interacting systems using the holographic duality discovered in string theory, mapping the quantum problem on a gravitational problem in one higher dimension, having as benefit offering a more general view on how dissipation emerges from such intricate quantum physical circumstances. We study here the elementary problem of a single vortex in two space dimensions, set in motion by a sudden quench in the background superflow formed in a finite density "Reissner-Nordstrom" holographic superconductor. This reveals a number of surprising outcomes addressing questions of principle. By fitting the trajectories unambiguously to the Hall-Vinen-Iordanskii phenomenological equation of motion we find that these are characterized by a large inertial mass at low temperature that however diminishes upon raising temperature. For a weak drive the drag is found to increase when temperature is lowered which reveals a simple shear drag associated with the viscous metallic vortex cores, supplemented by a conventional normal fluid component at higher temperatures. For a strong drive we discover a novel dynamical phenomenon: the core of the vortex deforms accompanied by a large increase of the drag force., Comment: 19 pages, 13 figures

Polycomb group proteins assemble into multi-protein complexes, known as Polycomb repressive complexes 1 and 2 (PRC1 and PRC2), that guide cell fate decisions during embryonic development. PRC1 forms an array of biochemically distinct canonical PRC1 (cPRC1) or non-canonical PRC1 (ncPRC1) complexes characterized by the mutually exclusive presence of PCGF (PCGF1-PCGF6) paralog subunit; however, whether each one of these subcomplexes fulfills a distinct role remains largely controversial. Here, by performing a CRISPR-based loss-of-function screen in embryonic stem cells (ESCs), we uncovered a previously unappreciated functional redundancy among PRC1 subcomplexes. Disruption of ncPRC1, but not cPRC1, displayed severe defects in ESC pluripotency. Remarkably, coablation of non-canonical and canonical PRC1 in ESCs resulted in exacerbation of the phenotype observed in the non-canonical PRC1-null ESCs, highlighting the importance of functional redundancy among PRC1 subcomplexes. Together, our studies demonstrate that PRC1 subcomplexes act redundantly to silence lineage-specific genes and ensure robust maintenance of ESC identity.

The investigation of two-dimensional (2D) materials has advanced into practical device applications, such as cascaded logic stages. However, incompatible electrical properties and inappropriate logic levels remain enormous challenges. In this work, a doping-free strategy is investigated by top gated (TG) MoS2 field-effect transistors (FETs) using various metal gates (Au, Cu, Ag, and Al). These metals with different work functions provide a convenient tuning knob for controlling threshold voltage (Vth) for MoS2 FETs. For instance, the Al electrode can create an extra electron doping (n-doping) behavior in the MoS2 TG-FETs due to a dipole effect at the gate-dielectric interface. In this work, by achieving matched electrical properties for the load transistor and the driver transistor in an inverter circuit, we successfully demonstrate wafer-scale MoS2 inverter arrays with an optimized inverter switching threshold voltage (VM) of 1.5 V and a DC voltage gain of 27 at a supply voltage (VDD) of 3 V. This work offers a novel scheme for the fabrication of fully integrated multistage logic circuits based on wafer-scale MoS2 film.

Background BRCA1 and BRCA2 (BRCA) mutation carriers face a high lifetime risk of developing ovarian cancer. Oral contraceptives are protective in this population; however, the impact of other types of contraception (e.g. intrauterine devices, implants, injections) is unknown. We undertook a matched case-control study to evaluate the relationship between type of contraception and risk of ovarian cancer among women with BRCA mutations. Methods A total of 1733 matched pairs were included in this analysis. Women were matched according to year of birth, date of study entry, country of residence, BRCA mutation type and history of breast cancer. Detailed information on hormonal, reproductive and lifestyle exposures were collected from a routinely administered questionnaire. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) associated with each contraceptive exposure. Results Ever use of any contraceptive was significantly associated with reduced risk of ovarian cancer (OR = 0.62; 95% CI 0.52–0.75; P < 0.0001), which was driven by significant inverse associations with oral contraceptives (OR = 0.66; 95% CI 0.54–0.79; P < 0.0001) and contraceptive implants (OR = 0.30; 95% CI 0.12–0.73; P = 0.008). We observed a similar effect with use of injections (OR = 0.37; 95% CI 0.10–1.38; P = 0.14), but this did not achieve significance. No significant associations were observed between patterns of intrauterine device use and risk of ovarian cancer. Conclusions These findings support a protective effect of oral contraceptives and implants on risk of ovarian cancer among women with BRCA mutations. The possible protective effect of injections requires further evaluation.

As multifunctional luminescence sensor, EU MOF has good thermal stability and water stability. It is used for the detection of Fe3+, Cr2O72−, CrO42− and aspartic acid in water system with low detection limit. And it has good recycling performance.

Persuasive technology in online shopping is proven to assist people while purchasing online. It is crucial to study how was the implementation of such successful persuasive technology in the e-commerce domain. Also, there are certain marketing strategies against consumers from different generational cohorts. Each generation has unique lifestyles, generational history, demographics, experiences, expectations and values that influence their buying behaviours. The persuasive design of e-commerce websites is related to the website conversion rate and is shown to support people throughout the online purchasing process. The objective of this research study is to evaluate the online persuasion criteria on two largest e-commerce websites in Malaysia; Lazada and Shopee through Persuasive System Design (PSD) principles. The four main categories of design technique applied in PSD are primary task support, dialogue support, credibility support and social support. The result shows that both selected e-commerce websites have applied 71.43% of the PSD principles. The most emphasize design technique in Lazada and Shopee is primary task support, followed by dialogue support. Most of the persuasive features in this model has implemented in both e-commerce websites. However, this research proved that the success of the e-commerce websites is related with the implemented persuasive feature which can be manipulated and implemented by other e-commerce websites.

Bell's palsy is a form of idiopathic, facial nerve palsy. Initial treatment includes the use of oral corticosteroids and/or antiviral agents, but facial paralysis may persist. Some surgeons suggest that surgical decompression of the facial nerve can be a beneficial, but the optimal surgical approach, extent of nerve decompression, and timing of surgery remain unclear.This study intended to evaluate the efficacy of delayed, facial nerve decompression for severe Bell's palsy (BP) and to explore the relationship of opportunity timing for operations, with postoperative recovery for facial nerve function.The research team performed a retrospective study.The study took place at Beijing Tiantan Hospital of Capital Medical University in Beijing, China.Participants were 45 patients who had been diagnosed with BP between 2015 and 2021 and who had undergone facial nerve decompression using the transmastoid approach, between 30 and 180 days after the onset of BP. According to the operation's timing, the research team divided the participants into three groups, consisting of participants who underwent surgery: (1) at 30-60-days after BP onset-19 participants, (2) at 61-90 days after BP onset-18 participants, and (3) at more than 90 days after BP onset-8 participants.The research team: (1) analyzed participants' demographic and preoperative and postoperative clinical characteristics, (2) compared the surgical outcomes with participants' House-Brackmann (HB) scales, and (3) analyzed the factors affecting the recovery of facial nerve function using logistic regression.Decompression surgery was effective for 29 participants (64.4%), with similar rates for participants who underwent surgery after 30-60 days (73.7%) and 61-90 days (77.8%), but the surgery' success was significantly higher for those groups than for participants who underwent surgery after90 days (12.5%), with P = .008 and P = .003, respectively. Multivariate logistic regression analysis showed that disease duration was the only factor significantly associated with the effectiveness of surgery (odds ratio = 120.337; 95% confidence interval 2.997-4832.267, P = .011).For patients with severe Bell's palsy with ineffective conservative treatment, surgery performed 30 to 90 days after the onset of paralysis can have therapeutic benefits, whereas surgery performed after 3 months is relatively ineffective.

Lacquer is widely used in ancient times. The antiques unearthed from Qin Terra-Cotta Warriors bear traces of lacquer painting massively. The lacquer paintings on the surface of the Qin Terra-Cotta Warriors fully demonstrate the characteristics and development level of lacquer painting at that time. However, the painted films unearthed appear crispy and fragile. In this study, six painted films are chosen from Pit.2 of the Qin Terra-Cotta Warriors and characterized by an ultra-depth-of-field microscope, a metalloscope, a scanning electron microscope, an energy dispersive spectrometer, and infrared spectroscopy. The results show that the painted films are lacquer films on the base layer of Qin terra-cotta warriors. In the wet alkaline environment, a fracture of the polymer chain along polymerization products of urushiol occurs, which produces soluble products containing benzene ring-related molecules, leading to lacquer films’ embrittlement and cracks. Lacquer films have aged.

There are few analyses of the 15 red blood group system antigen coding genes found in the Yunnan Yi nationality. This has caused many poteintial dangers relating to clinical blood transfusion. In this report, the coding genes and distribution of 15 blood group antigens system in the Yi nationality were tested and compared with those of Han nationality and other ethnic minorities.The samples came from the healthy subjects in the first people's Hospital of Qujing, Yunnan Province. Two hundred and three Yunnan Yi and 197 Han nationality individuals were included. Thirty-three blood group antigens with a low frequency from the 15 blood group systems of Yunnan Yi blood donors were genotyped and analyzed by PCR-SSP. Sanger sequencing was used to detect A4GALT from the Yunnan Yi nationality. TheThe ABO blood group examination results for the Yi nationality and the local Han nationality in Qujing City, Yunnan Province, showed the majority were type A and type O, while the least prevalent was type AB. RhD+ accounts for more than 98% of the Yi and Han populations. There was a significant difference in ABO blood group antigen distribution between these two nationalities (Yunnan Yi nationality has a unique genetic background. There are some significantly different distributions of blood group system genes with a low frequency in different regions and groups in China. Multiple mutations in the A4GALT gene of the P1PK blood group system may be related to their environment and ethnic evolution.

The A-kinase anchoring protein 150 (AKAP150) organizes kinases and phosphatases to regulate AMPA receptors (AMPARs) that are pivotal for synaptic plasticity. AKAP150 itself undergoes S-palmitoylation. However, the roles of AKAP150 and its palmitoylation in spinal nociceptive processing remain unknown. In this study, we found that intraplantar injection of complete Freund's adjuvant (CFA) significantly increased the synaptic expression of AKAP150 and caused a reorganization of AKAP150 signaling complex in spinal dorsal horn. Knockdown of AKAP150 or interruption of its interactions with kinases effectively suppressed the CFA-induced synaptic expression of GluA1 subunit of AMPARs. Our data also showed that an upregulation of AKAP150 palmitoylation was involved in the synaptic redistribution of AKAP150. Inhibition of AKAP150 palmitoylation by expression of palmitoylation-defective mutant AKAP150 (C36, 123S) effectively repressed the CFA-induced phosphorylation and synaptic expression of GluA1 subunit, meanwhile, attenuated the development of mechanical allodynia and thermal hyperalgesia. Furthermore, we found that an increased expression of palmitoyl acyltransferase ZDHHC2 contributed to the upregulation of AKAP150 palmitoylation and GluA1 accumulation in inflamed mouse. These data indicated that AKAP150 and its palmitoylation were involved in AMPA receptor-dependent modification of nociceptive transmission, and the manipulations of AKAP150 signaling complex and palmitoylation might serve as potential therapeutic strategies for persistent pain after inflammation.

Many statistical methodologies for high-dimensional data assume the population is normal. Although a few multivariate normality tests have been proposed, to the best of our knowledge, none of them ...

Xianglian pill (XLP), a traditional Chinese formula, is widely used as treatment for ulcerative colitis (UC) in China. However, the mechanism of its therapeutic effect is still unclear.Our previous studies showed a low oral bioavailability and a predominant distribution of major XLP ingredients in the gut. In the present study, we aimed to explore the mechanism of action of XLP on UC with respect to the regulation of gut microecology.UC model rats established using 5% dextran sulfate sodium were treated with XLP. After the treatment period, bodyweight, colon length, histopathology, and inflammatory changes were evaluated. Further, changes in gut microbiota structure were detected via 16S rRNA sequencing, and microbial metabolites in feces were analyzed via a metabolomic assay. Antibiotic intervention and fecal microbiota transplantation were also employed to explore the involvement of gut microbiota, while the level of regulatory T cells (Tregs) in mesenteric lymph nodes was determined via flow cytometry. Transcriptome sequencing was also performed to determine colonic gene changes.XLP alleviated colonic injury, inflammation, and gut microbial dysbiosis in UC model rats and also changed microbial metabolite levels. Particularly, it significantly decreased succinate level in the tyrosine pathway. We also observed that fecal microbiota derived from XLP-treated rats conferred resilience to UC model rats. However, this therapeutic effect of XLP on UC was inhibited by succinate. Moreover, XLP increased the level of anti-inflammatory cellular Tregs via gut microbiota. However, this beneficial effect was counteracted by succinate supplementation. Further, XLP induced the differentiation of Treg possibly by the regulation of the PHD2/HIF-1α pathway via decreasing microbial succinate production.Our findings indicated that XLP exerts its therapeutic effects on UC mainly via the gut microbiota-succinate-Treg differentiation axis.

Background LCAR-B38M is a chimeric antigen receptor T cell product with two binding domains targeting B cell maturation antigen. Our previous reports showed a remarkable efficacy of LCAR-B38M in patients with relapsed/refractory multiple myeloma (RRMM) at a median follow-up of 2 years. Here, we report long-term safety and efficacy data from a median follow-up of 4 years. Methods LEGEND-2 was a phase 1, single-arm, open-label study conducted in four registered sites in China. Seventy-four participants with RRMM received LCAR-B38M treatment. Lymphodepletion was performed using cyclophosphamide or cyclophosphamide plus fludarabine. LCAR-B38M, at a median dose of 0.513 × 106 cells/kg, was intravenously administered either in three split infusions or in a single infusion. The primary objective was the safety of LCAR-B38M, and the secondary objective was efficacy. Results As of May 25, 2021, the median follow-up was 47.8 months. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were observed in 45/74 (60.8%) patients. Cytokine release syndrome (CRS) occurred in 68/74 (91.9%) cases; 7 (9.5%) had grade ≥ 3 CRS. One patient experienced grade 1 central nervous system toxicity. The overall response rate was 87.8%. Fifty-four out of 74 (73.0%) patients achieved complete response. The median progression-free survival was 18.0 months, and the median overall survival for all patients was not reached. The median duration of response was 23.3 months. Four patients experienced viral infection more than 6 months post-infusion, and four patients developed second primary non-hematological malignancies at a median time of 11.5 months post-CAR-T cell transfer. Conclusions The 4-year follow-up data of LCAR-B38M therapy demonstrated a favorable long-term safety profile and a durable response in patients with RRMM. Trial registration Clinicaltrials.gov NCT03090659 (retrospectively registered on March 27, 2017); ChiCTR-ONH-17012285.

Enantioselective Ni-catalyzed C(spsup3/sup)-H bond activation remains an elusive challenge. Herein, we used phosphine oxide-ligated Ni-Al bimetallic catalyst to realize enantioselective Ni-catalyzed aliphatic C(spsup3/sup)-H activation of formamides, providing a series of chiral N-containing heterocycles in 40-95 % yield and 70-95 % ee.

Salt enrichment in the topsoil, owing to one-way migration of moisture from earthen sites to air environment, is an important inducement to weathering of sites and relics, such as efflorescence, recess, slice-peeling, which becomes the most important challenge to the preservation of unearthed sites and relics. Further, salt enrichments in the topsoil of undulating earthen sites are usually inhomogeneous such that it is difficult to precisely prevent the deterioration from happening of salt enrichment in the topsoil. A case study of salt enrichment at the K9901 funerary pit of Emperor Qin’s Mausoleum Site Museum was conducted by soil column experiment and numerical simulation. The water and salt transport in the earthen sites were simulated and analyzed by HYDRUS software. The simulation of the salt enrichment process at the earthen sites demonstrated that the enrichment of soluble salt ions mainly occurs on the surface of rammed earth and increases annually; the salt damage at the earthen sites can be effectively delayed by taking an environmental control measure. These results provide a reference for the prevention of salt damage at earthen sites and facilitate the daily management of earthen sites.

In this paper, we consider the inverse problem for identifying the initial value problem of the time–space fractional nonlinear diffusion equation. The uniqueness of the solution is proved by taking the fixed point theorem of Banach compression, and the ill-posedness of the problem is analyzed through the exact solution. The quasi-boundary regularization method is chosen to solve the ill-posed problem, and the error estimate between the regularization solution and the exact solution is given. Moreover, several numerical examples are chosen to prove the effectiveness of the quasi-boundary regularization method. Finally, our method can be used to solve high dimensional time–space fractional nonlinear diffusion equation, especially in cylindrical and spherical symmetric regions.

Photochemistry to prepare platinum nanoparticles (Pt NPs) is an essential way to control Pt NPs catalyst size distribution. This article reports a series of morphologically controlled syntheses of Pt NPs loaded on modified carbon nanotube (Pt-CNTs). In the synthesis, Polyethylene glycol (PEG) participates in reactions both as a reducing agent and a stabilizer. Visible light irradiation was adopted as a kinetic controlling approach. Typical 4-nitrophenol (4-NP) reduction was adopted to probe the catalytic performances. Characterizations prove that visible light irradiation is an effective way to control the reaction process. In the optimized reaction conditions, i.e., when the ratio PEG:H2O is 1:9, and the pH is 10, the as-prepared Pt NPs are consequently in a very narrow sized distribution with an average diameter of 1.29 nm. The Pt-CNTs present a high reaction rate constant of 0.624 min-1 in the catalytic reduction of 4-NP. All the research results are beneficial for exploring more green chemistry and facile photochemical approaches in the controlled preparation of Pt nanocatalysts.

Evidence-based decision making often relies on meta-analyzing multiple studies, which enables more precise estimation and investigation of generalizability. Integrative analysis of multiple heterogeneous studies is, however, highly challenging in the ultra high dimensional setting. The challenge is even more pronounced when the individual level data cannot be shared across studies, known as DataSHIELD constraint (Wolfson et al., 2010). Under sparse regression models that are assumed to be similar yet not identical across studies, we propose in this paper a novel integrative estimation procedure for data-Shielding High-dimensional Integrative Regression (SHIR). SHIR protects individual data through summary-statistics-based integrating procedure, accommodates between study heterogeneity in both the covariate distribution and model parameters, and attains consistent variable selection. Theoretically, SHIR is statistically more efficient than the existing distributed approaches that integrate debiased LASSO estimators from the local sites. Furthermore, the estimation error incurred by aggregating derived data is negligible compared to the statistical minimax rate and SHIR is shown to be asymptotically equivalent in estimation to the ideal estimator obtained by sharing all data. The finite-sample performance of our method is studied and compared with existing approaches via extensive simulation settings. We further illustrate the utility of SHIR to derive phenotyping algorithms for coronary artery disease using electronic health records data from multiple chronic disease cohorts.

OBJECTIVE: To analyze the clinical characteristics of unilateral acoustic neuroma(AN) with normal hearing, so as to provide evidence for early identification AN. METHODS: Clinical datas from 73 patients of unilateral AN with normal hearing of Otorhinolaryngology Head and Neck Surgery of Beijing Tiantan Hospital affiliated of Capital Medical University from August 2019 to April 2022 admitted to department were retrospectively analyzed. All patients underwent pure tone audiometry(PTA), speech discrimination score(SDS), auditory brainstem response(ABR), distortion product otoacoustic emission(DPOAE) and head enhanced MRI. RESULTS: The incidence of normal hearing among patients with AN was 10.7%. Male∶female=1∶2.2; the mean age of the patients was(37.3±9.4) years; the mean tumor size was(24.2±11.2) mm. Tinnitus was the most common reason for visit; the patients who had headache and dizziness had larger tumors. Surgery was the main treatment, and the patients who underwent surgery had larger tumors than those of follow-up. Heterogeneous tumors were the most common type of MRI, homogeneous tumors were smaller than heterogeneous and cystic tumors. The sensitivity of ABR in the diagnosis of AN with normal hearing was 95.9%, and that of ≥20 mm tumors was 100%; prolonged Ⅴ-waves were the most common, patients with Ⅴ-wave deletion had larger tumors than those with normal or prolonged Ⅴ-waves. Patients who had the longer the Ⅴ-wave and the longer difference between Ⅰ-Ⅴ wave had larger tumors. DPOAE was not elicited at full frequency in 11 patients. There was no statistically significant difference in age among patients with different symptoms, treatments, types of MRI, ABR and DPOAE. CONCLUSION: AN of normal hearing was most common in 30-39 years old women. Patients had different symptoms, phenotypes of MRI and ABR. Patients with normal hearing who had tinnitus, dizziness, headache, facial paraesthesia, and recovery after sudden haring loss can be further examination of ABR and DPOAE for early identification AN. The sensitivity of ABR in diagnosis of hearing normal AN was 95.9%, and the abnormal type of Ⅴ-wave is related to tumor size.

Final urine volume and concentration are defined by water reabsorption through the water channel proteins aquaporin (AQP)-2, -3 and -4 in the collecting duct. However, the transcriptional regulation of these AQPs is not well understood. The Hippo/Yes-associated protein 1 (YAP) pathway plays an important role in organ size control and tissue homeostasis. When the Hippo pathway including the Mst1/Mst2 kinases is inhibited, YAP is activated and functions as a transcription co-activator. Our previous work revealed a pathological role of tubular YAP activation in chronic kidney disease, but the physiological role of YAP in the kidney remains to be established. Here, we found that tubule-specific Yap knockout mice showed increased urine output and decreased urinary osmolality. Decreases in Aqp2, -3 and -4 mRNA and protein abundance in the kidney were evident in Yap knockout mice. Analysis of Mst1/Mst2 double knockout and Mst1/Mst2/Yap triple knockout mice showed that expression of Aqp2 and Aqp4 but not Aqp3 was dependent on YAP. Furthermore, YAP was recruited to the promoters of the Aqp2 and Aqp4 genes and stimulated their transcription. Interestingly, YAP was found to interact with transcription factors GATA2, GATA3 and NFATc1. These three factors promoted Aqp2 transcription in a YAP dependent manner in collecting duct cells. These three factors also promoted Aqp4 transcription whereas only GATA2 and GATA3 enhanced Aqp3 transcription. Thus, our results suggest that YAP promotes Aqp2 and Aqp4 transcription, interacts with GATA2, GATA3 and NFATc1 to control Aqp2 expression, while Aqp-2, -3 and -4 exploit overlapping mechanisms for their baseline transcriptional regulation.

2D semiconductors, such as molybdenum disulfide (MoS

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases in which neuroinflammation plays pivotal roles. An important mechanism of neuroinflammation is the NLRP3 inflammasome activation that has been implicated in PD pathogenesis. In this perspective, we will discuss the relationship of some key PD-associated proteins including α-synuclein and Parkin and their contribution to inflammasome activation. We will also review promising inhibitors of NLRP3 inflammasome pathway that have potential as novel PD therapeutics. Finally, we will provide a summary of current and potential in vitro and in vivo models that are available for therapeutic discovery and development.

In this paper, X-ray diffraction spectroscopy (XRD), Raman spectroscopy (RS), firing temperature analysis, pore size distribution analysis, Fourier infrared spectroscopy (FTIR), scanning electron microscopy-energy dispersive spectroscopy (SEM–EDS), and transmission electron microscopy (TEM) were utilized to analyze the unearthed vulnerable terracotta figures of Emperor Qin Shihuang's Terracotta Army, as well as the unknown precipitated white crystals and black substances. The results show that the firing temperature of the vulnerable terracotta figure is much lower than those of similar terracotta figures and red terracotta figures with good texture. The pore size of this kind of vulnerable pottery is smaller and the specific surface area is larger. In the pores, there is an alkaline solution containing Ca2+ that accounted for approximately 4.3% of the total mass of the sample. Along with the fracture of the delicate pottery matrix, the solution in the pores migrated to the fracture surface and chemically reacted with CO2 in the air, generating a layer of white calcium carbonate crust. The black matter on the fracture surface of the vulnerable terracotta figure is mainly composed of amorphous carbon and graphitized carbon, which shows high activity under the catalysis of Fe and Ti elements and alkaline soil. The discovery and analysis of amorphous carbon, graphitized carbon, and white calcium carbonate crystals on the fracture surface of the Qin Shihuang’s Terracotta Army provide a theoretical foundation for in-depth analysis of the terracotta warriors and horses' composition and structure, as well as scientific protection and restoration, and the stability of the original site display.

Background The immunogenicity of the liver tumor microenvironment is clinically heterogeneous and mysterious. The insight into the role of immune cells including tumor-infiltrating lymphocytes (TILs) and chemokine networks, might enable optimal patient selection for immunotherapy. In this study, we aimed at characterizing the liver cancer immune subtypes linked to chemokines and associating with the patient characteristics and clinical outcomes. Methods We analyzed the immune cells and chemokine signatures of human liver cancer using The Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) database profiling of 110 normal liver tissues and 369 liver tumor patients. We performed hierarchical clustering to the chemokine expression by applying immune cells status to categorize the CCL5-related chemokine in liver tumors. The separation was characterized by dividing the liver tumor patients into CCL5-high and low subtypes. Results Our results showed that the high expression of myeloid-derived suppressor cells (MDSCs) is associated with a decrease in effector T cells expressing PRF1 in liver tumor progression. The chemokines and immune cells in CCL-5-high subtype including CCR5, MDSCs and effector T cells, are significantly associated with CCL5 and a potential predictive clinical benefit. The estimated odds for CCL5-low subtype liver tumors were higher than CCL5-high subtype liver tumors particularly in the stage IV tumors (OR = 3.54; 95 % CI: 0.36, 34.92). Our data demonstrated that the CCL5-high subtype significantly improved OS (p = 0.0379, hazard ratio 0.67; 95% CI 0.43, 0.98), DFI (p = 0.0104, hazard ratio 0.63; 95% CI 0.44, 0.90), PFI (p = 0.0066, hazard ratio 0.64; 95% CI 0.46, 0.89) and working performance status when compared to the CCL5-low subtype. Conclusion Our findings provide a novel perspective of liver cancer chemokine subtypes linked to immune cells. A suitable therapy that can effectively activate effector T cells and inhibit MDSCs targeting chemokines might support the magnitude of lymphocytic infiltration in liver tumors, and should be considered for the design of precision therapies targeting the tumor and its immune microenvironment. The chemokine signatures in the CCL5-subtype are a valuable resource for future research to help identify clinically relevant biomarkers.

BackgroundStudies assessing links between maternal diet and pregnancy outcomes have focused predominantly on individual nutrients or foods. However, nutrients are typically consumed in combinations of foods or beverages (i.e., dietary patterns). Taking into account the diet as a whole appreciates that nutrient absorption and metabolism are influenced by other nutrients and the food matrix.ObjectiveThe aim of this study was to investigate the relationship between dietary pattern consumption in early pregnancy and pregnancy/infant outcomes, including gestational diabetes mellitus, gestational weight gain, preeclampsia, placental weight, gestational age at delivery, small-for-gestational-age, large-for-gestational-age, macrosomia, measures of infant body composition, and scores on two main indices of the Bayley Scales of Infant Development [Mental Development Index (MDI) and the Psychomotor Development Index (PDI)] at 12 months.DesignOur study included 1,437 participants from a mother-infant cohort in Chongqing, China. Maternal diet was assessed using a 96-item food frequency questionnaire at 11–14 weeks gestation. Dietary patterns were constructed using principal component analysis. Multivariate regressions were performed to assess associations between maternal dietary pattern scores and pregnancy and infant outcomes, adjusting for confounders.ResultsTwo dietary patterns were derived: a pattern high in pasta, sweetened beverages, and oils and condiments (PSO-based dietary pattern) and a pattern high in fish, poultry, and vegetables (FPV-based dietary pattern). Higher scores on the PSO-based dietary pattern were associated with lower infant standardized scores on the PDI of the Bayley Scales of Infant Development, β (95% confidence interval) = −1.276 (−2.392, −0.160); lower placental weight, β (95% CI) = −6.413 (−12.352g, −0.473); and higher infant's tricep skinfold thickness at 6 weeks of age. β (95% CI) = 0.279 (0.033, 0.526). Higher scores on the FPV-based dietary pattern were associated with higher gestational weight gain between visit 1 (11–14 week's gestation) and 3 (32–34 week's gestation). β (95% CI) = 25.612 (13.255, 37.969). No significant associations were observed between dietary pattern scores and the remaining pregnancy/infant outcomes investigated or MDI scores on the Bayley Scales of Infant Development. This was the first study to investigate the association between dietary patterns in early pregnancy and infant neurocognition in a Chinese cohort.

Background: The use of herbal medicines has tremendously increased over the past few decades. Case reports and controlled clinical investigations of herbal-drug interactions have been reported. Since Cytochrome P450 (CYP) enzymes play an important role in drug interactions. The evaluation of the influence of herbal medicines on the activities of CYPs is beneficial to promote scientific and rational clinical use of herbal medicines. Objective: Herein, we aimed to develop and validate a method to simultaneously quantify seven CYP cocktail probe drugs consisting of phenacetin (PNC), bupropion (BPP), losartan potassium (LK), omeprazole (OMP), dextromethorphan (DM), chlorzoxazone (CZZ) and midazolam (MDZ) and their respective metabolites in a single acquisition run and use this method to evaluate the influence of Zhuanggu Guanjie Pill (ZGGJP) on seven CYPs. Methods: A cost-effective and simple UHPLC-(±)ESI-MS/MS method for simultaneous determination of seven probe drugs and metabolites in rat plasma was developed and validated. Male and female rats were randomly divided into three groups and treated with 1.2 g/kg/d ZGGJP, 5 g/kg/d ZGGJP and 0.5% CMC-Na for 14 consecutive days. After 24 h of the last administration, all rats were administrated orally with probe drugs. The influence of ZGGJP on the CYPs was carried out by comparing the metabolic ratio (Cmax, AUC0-t) of metabolites/probe drugs in rats. Results: The calibration curves were linear, with correlation coefficient > 0.99 for seven probe drugs and their corresponding metabolites. Intra- and inter-day precisions were not greater than 15% RSD and the accuracies were within ±15% of nominal concentrations. The ZGGJP showed significant inductive effect on CYP1A2, CYP2B6, CYP2C9 and CYP3A in male and female rats. Conclusion: ZGGJP had inductive effects on CYP1A2, CYP2B6, CYP2C9 and CYP3A in male and female rats.

ObjectiveMaternal abnormal fatty acid desaturation has previously been linked to gestational diabetes mellitus (GDM). However, few studies have investigated this relationship longitudinally throughout pregnancy. In this study, we investigated the relationship between GDM and desaturase activities across the pregnancy trimesters.MethodsA total of 661 women (GDM = 189, non-GDM = 472) were selected from the Complex Lipids in Mothers and Babies (CLIMB) cohort study. Clinical information and maternal serum were collected at 11–14, 22–28, and 32–34 weeks of gestation. Totally, 20 serum fatty acids were quantified using gas chromatography–mass spectrometry (GC-MS) analysis at each timepoint. Polyunsaturated fatty acid (PUFA) product-to-precursor ratios were used to estimate desaturase and elongase activities including delta-5 desaturase, delta-6 desaturase, stearoyl-CoA desaturase, and elongase.ResultsAfter adjusting for major potential confounders including maternal age, BMI, primiparity, smoking, and alcohol consumption, we observed a significant increase in the levels of γ-linolenic acid (GLA) and eicosatrienoic acid (DGLA) in the first trimester of women with GDM, whereas GLA and DGLA were reduced in the third trimester, when compared to the non-GDM group. Arachidonic acid (AA) showed an upward trend in the GDM group throughout pregnancy. Estimated delta-6 desaturase and delta-5 desaturase activity were elevated in the first trimester (OR = 1.40, 95% CI 1.03–1.91; OR = 0.56, 95% CI 0.32–0.96) but attenuated in the third trimester (OR = 0.78, 95% CI 0.58–1.07; OR = 2.64, 95% CI 1.46–4.78) in GDM pregnancies, respective to controls. Estimated delta-9–18 desaturase activity (OR = 3.70, 95% CI 1.49–9.19) was increased in women with GDM in later pregnancy.ConclusionsOur study highlights the potential importance of fatty acid desaturase activities, particularly estimated delta-5 desaturase and delta-9–18 desaturase in the pathophysiology of GDM. These findings may have applications for the early diagnosis and management of GDM.

Summary Polycomb group (PcG) proteins exist in distinct multi-protein complexes and play a central role in silencing developmental genes, yet the underlying mechanisms remain elusive. Here, we show that deficiency of retinoblastoma binding protein 4 (RBBP4), a component of the Polycomb repressive complex 2 (PRC2), in embryonic stem cells (ESCs) leads to spontaneous differentiation into mesendodermal lineages. We further show that Rbbp4 and core PRC2 share an important number of common genomic targets, encoding regulators involved in early germ layer specification. Moreover, we find that Rbbp4 is absolutely essential for genomic targeting of PRC2 to a subset of developmental genes. Interestingly, we demonstrate that Rbbp4 is necessary for sustaining the expression of Oct4 and Sox2 and that the forced co-expression of Oct4 and Sox2 fully rescues the pluripotency of Rbbp4-null ESCs. Therefore, our study indicates that Rbbp4 links maintenance of the pluripotency regulatory network with repression of mesendoderm lineages., Graphical Abstract, Highlights • RBBP4 deficiency in ESCs leads to spontaneous differentiation into mesendodermal lineages • Rbbp4 binding sites in ESCs substantially overlap with PRC2 binding • Rbbp4 is absolutely essential for PRC2 chromatin occupancy • Rbbp4 is necessary for sustaining the expression levels of Oct4 and Sox2, Polycomb group (PcG) proteins play a critical role in silencing developmental genes, yet the underlying mechanisms remain elusive. Yikai et al. report that PcG protein Rbbp4 represses developmental gene expression by recruiting PRC2 to the genes' promoter regions, thereby maintaining stem cell self-renewal and identity.

Colorectal cancer (CRC) is a common cancer with high metastatic property. Circular RNAs (circRNAs) have important involvement in cancer processes. This study focused on the regulation of circRNA RAD23 homologue B (circRAD23B) in CRC. The levels of circRAD23B, microRNA-1205 (miR-1205), and tripartite motif-44 (TRIM44) were examined by quantitative real-time polymerase chain reaction (qRT-PCR). Functional analyses were performed by Cell Counting Kit-8 (CCK-8) for cell proliferation, flow cytometry for cell cycle or cell apoptosis, and transwell assay for cell migration and invasion. Western blot was administrated for protein detection. The interaction of targets was analyzed by dual-luciferase reporter and RNA pull-down assays. The in vivo experiment was conducted via xenograft tumor in mice. We identified that circRAD23B was overexpressed in CRC tissues and cells. CRC cell proliferation, cell cycle progression, and cell metastasis were inhibited, while apoptosis was promoted by downregulating circRAD23B. Target analysis indicated that circRAD23B-targeted miR-1205 and TRIM44 were downstream genes of miR-1205. Moreover, the antitumor response of circRAD23B downregulation and miR-1205 overexpression was, respectively, achieved by increasing miR-1205 and decreasing TRIM44. CircRAD23B could regulate TRIM44 level by sponging miR-1205. In vivo, circRAD23B knockdown also reduced CRC tumorigenesis via the miR-1205/TRIM44 axis. These results suggested that the inhibition of circRAD23B retarded the progression of CRC via acting on the miR-1205/TRIM44 axis. CircRAD23B might be a novel target in CRC treatment.

Exploiting spatial patterns in large-scale multiple testing promises to improve both power and interpretability of false discovery rate (FDR) analyses. This article develops a new class of locally ...

A highly selective turn-on fluorescent and naked-eye colourimetric dual-channel probe for cyanide anions (CNˉ) has been designed and characterized. In the mixed solution (DMSO / H2O, 9:1, v / v), only CNˉ could cause an increase in the UV absorption intensity and the corresponding fluorescence intensity increased, and other anions had no significant effect on the probe. After treatment with cyanide in the probe solution, the solution showed a noticeable colour change, from light yellow to purple. Moreover, a fluorescence spectrophotometer can be used to observe that the fluorescence intensity of the solution is significantly enhanced. The response of the colourimetric and fluorescent dual-channel probe to CNˉ was attributed to nucleophilic addition, and the mechanism was determined by 1H NMR spectroscopy. In addition, this probe was used to detect CNˉ in actual water samples, including river water, drinking water, and tap water. The spiked CNˉ recovery rate is very high (97.2%-100.06%), and analytical precision is also very high (RSD

Based on tetraphenylethylene as the skeleton, two novel salamo-type fluorescent probes (TPES1 = 2-hydroxy-1-naphthaldehyde O-(3-(((-2-hydroxy-5-(1,2,2-triphenylvinyl)benzylidene)amino)oxy)propyl) oxime and TPES2 = bis(2-hydroxy-1-naphthaldehyde O-(3-(((2-hydroxy-5-(1,2,2-triphenylvinyl)benzylidene)amino)oxy)propyl) dioxime) were designed and synthesized. Through the colorimetric and fluorescence dual-channel modes, cyanide ions could be specifically recognized by the two probe molecules. Interestingly, the probes TPES1 and TPES2 exhibited completely different spectral behaviors during the recognition process. Of the two, the TPES1 molecule is a ratio-type fluorescent probe, and double fluorescence emission peaks appeared during the titration process. The reason for this phenomenon is due to the rotation of the C–C single bond in tetraphenylethylene, causing the solution system to contain molecules in two states. On the other hand, the TPES2 molecule is a fluorescence-enhanced probe that has undergone two reaction processes of deprotonation and addition reaction successively, causing the fluorescence intensity to increase continuously. Theoretical calculations indicated that the configuration of probe TPES1 is reversed after interacting with cyanide ions (CN−). By calculating the minimum detection limits of TPES1 and TPES2 to CN−, the LOD values were 8.56 × 10−8 M and 5.37 × 10−8 M, respectively. In addition, probe-based test strips have been prepared for quick and simple detection of cyanide ions.

In this paper, the deformation of the platform and canopy of a high-speed railway station is studied, and an online monitoring system for platform canopy deformation is designed to solve the problem of online monitoring of platform canopy deformation. Due to the conventional one-dimensional measurement has been difficult to meet the needs of high-speed railway industrial production and daily life. Nowadays, laser radar and binocular cameras for three-dimensional data measurement have gradually emerged. At present, there is almost no three-dimensional data acquisition equipment with high measurement accuracy, low price, and a high degree of automation in the market. Given the lack of this equipment in the market, this paper presents a three-dimensional data acquisition system based on a laser rangefinder. By collecting, processing, and analyzing the data of the platform and canopy, the purpose of prediction can be achieved, and then the abnormal response, damage, and degradation of the structure can be found in time. The study shows that the monitoring system is helpful to detect deformation and give early warning, and effectively prevent the occurrence of hazards.

Digital technologies are playing an increasing role in the global response to tuberculosis (TB), however their effectiveness and impact are often shaped in the context in which they are implemented. Implementation research can help facilitate the effective introduction of digital health technologies in TB programmes. In 2020, the Implementation Research for Digital Technologies and TB online toolkit (IR4DTB) was developed and launched by the Special Programme for Research and Training in Tropical Diseases, and the Global TB Programme at the World Health Organization (WHO), to build local capacity for IR and promote the effective use of digital technologies within TB programmes. This paper describes the development and piloting of the IR4DTB toolkit, a self-learning tool designed for TB programme implementers. The toolkit comprises six modules reflecting key steps of the IR process, practical instructions and guidance on how to complete these steps, and real-word case studies to illustrate key learning points. This paper also describes the launch of the IR4DTB during a five-day training workshop with TB staff from China, Uzbekistan, Pakistan, Malaysia. The workshop included facilitated sessions on the IR4DTB modules, and provided an opportunity for participants to work with facilitators to develop a comprehensive IR proposal addressing an identified challenge related to the implementation and/or scale-up of digital health technologies for TB care in their home country. Post-workshop evaluation revealed high level of satisfaction among participants with the workshop content and format. The IR4DTB toolkit is a replicable model which can be used to strengthen the TB staff capacity to innovate within a culture of continuous collection of evidence. Through continued trainings and adaptation of the toolkit alongside the integration of digital technologies within TB prevention and care, this model has the potential to contribute directly to all components of the End TB Strategy.