Dual-quartet phosphorescent emission in the open-shell M1Ag13 (M = Pt, Pd) nanoclusters.

Dual emission (DE) in nanoclusters (NCs) is considerably significant in the research and application of ratiometric sensing, bioimaging, and novel optoelectronic devices. Exploring the DE mechanism in open-shell NCs with doublet or quartet emissions remains challenging because synthesizing open-shell NCs is difficult due to their inherent instability. Here, we synthesize two dual-emissive M1Ag13(PFBT)6(TPP)7 (M = Pt, Pd; PFBT = pentafluorobenzenethiol; TPP = triphenylphosphine) NCs with a 7-electron open-shell configuration to reveal the DE mechanism. Both NCs comprise a crown-like M1Ag11 kernel with Pt or Pd in the center surrounded by five PPh3 ligands and two Ag(SR)3(PPh3) motifs. The combined experimental and theoretical studies revealed the origin of DE in Pt1Ag13 and Pd1Ag13. Specifically, the high-energy visible emission and the low-energy near-infrared emission arise from two distinct quartet excited states: the core-shell charge transfer and core-based states, respectively. Moreover, PFBT ligands are found to play an important role in the existence of DE, as its low-lying π* levels result in energetically accessible core-shell transitions. This novel report on the dual-quartet phosphorescent emission in NCs with an open-shell electronic configuration advances insights into the origin of dual-emissive NCs and promotes their potential application in magnetoluminescence and novel optoelectronic devices.

[Source Apportionment of Morphine in Wastewater].

It is a new approach to identify legal or illegal use of morphine through information on municipal wastewater. However, the sources of morphine in wastewater are complex, and distinguishing the contribution of different sources has become a key issue. A total of 262 influent samples from 61 representative wastewater treatment plants in a typical city were collected from October 2022 to March 2023. The concentrations of morphine, codeine, thebaine, papaverine, noscapine, and monoacetylmorphine were analyzed in wastewater and poppy straws. Combined with the proportion of alkaloids in poppy straws, the source analysis of alkaloids in wastewater was analyzed using the ratio method and positive matrix factorization model (PMF). Only five alkaloids were detected in wastewater, and monoacetylmorphine, a metabolite of heroin, was not detected. The concentrations of morphine and codeine were significantly higher than those of noscapine, papaverine, and thebaine. By constructing the ratios of codeine/(morphine + codeine) and noscapine/(noscapine + codeine), the source of poppy straw could be qualitatively distinguished. The PMF results showed that three sources of morphine for medical use, poppy straw, and codeine contributed 44.9%, 43.7%, and 9.4%, respectively. The different sources varied in these months due to the COVID-19 and influenza A outbreaks, in which the use of drugs containing poppy straws and codeine was the main source, whereas the use of morphine analgesics remained relatively stable. Inventory analysis further demonstrated the reliability of the source contributions from the PMF model, and morphine was not abused in this city.

Constructing CoNi-LDH/Fe MOF/NF Heterostructure Catalyst for Energy-Efficient OER and UOR at High Current Density.

The sluggish kinetics of the oxygen evolution reaction (OER) always results in a high overpotential at the anode of water electrolysis and an excessive electric energy consumption, which has been a major obstacle for hydrogen production through water electrolysis. In this study, we present a CoNi-LDH/Fe MOF/NF heterostructure catalyst with nanoneedle array morphology for the OER. In 1.0 M KOH solution, the heterostructure catalyst only required overpotentials of 275 and 305 mV to achieve high current densities of 500 and 1000 mA/cm2 for OER, respectively. The catalytic activities are much higher than those of the reference single-component CoNi-LDH/NF and Fe MOF/NF catalysts. The improved catalytic performance of the heterostructure catalyst can be ascribed to the synergistic effect of CoNi-LDH and Fe MOF. In particular, when the anodic OER is replaced with the urea oxidation reaction (UOR), which has a relatively lower thermodynamic equilibrium potential and is expected to reduce the cell voltage, the overpotentials required to achieve the same current densities can be reduced by 80 and 40 mV, respectively. The cell voltage required to drive overall urea splitting (OUS) is only 1.55 V at 100 mA/cm2 in the Pt/C/NF||CoNi-LDH/Fe MOF/NF two-electrode electrolytic cell. This value is 60 mV lower compared with that required for overall water splitting (OWS). Our results indicate that a reasonable construction of a heterostructure catalyst can significantly give rise to higher electrocatalytic performance, and using UOR to replace the anodic OER of the OWS can greatly reduce the electrolytic energy consumption.

Application of serum peptidomics for Parkinson's disease in SNCA-A30P mice.

Intraneuronal inclusions of alpha-synuclein (α-synuclein, α-syn) are commonly found in the brain of patients with Parkinson's disease (PD). The pathogenesis of the abundant α-syn protein in the blood has been extensively studied to understand its properties better. In recent years, peptidome analysis has received increasing attention. In this study, we identified and analyzed serum peptides from wild-type (WT) and the (Thy-1)-h[A30P] alpha-synuclein transgenic mice (SNCA-A30P mice) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). One thousand eight hundred fifty-six peptides from 771 proteins were analyzed. Among them, 151 peptides from 107 proteins were significantly differentially expressed. The glycoprotein VI platelet pathway (GP6) was the pathway's most significant differentially expressed signaling pathway. Cleavage sites of the differentially expressed peptides may reflect protease distribution and activity. We selected the most significantly differentially expressed peptide, VGGDPI, and found that it contained cathepsin K (Ctsk) and trypsin-1 cleavage sites, suggesting that Ctsk and trypsin-1 may be key peptidases in PD. α-syn is a protein associated with the pathogenesis of PD. mutations in several genes, including SNCA, which encodes α-syn, are associated with the development of PD. Bioinformatics analysis of the physiological pathways related to SNCA genes and apoptosis genes found the five most markedly up-regulated proteins: formin homology 2 domain-containing 1 (FHOD1), insulin receptor substrate 1(IRS1), TRPM8 channel-associated factor 1 (TCAF1), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and interleukin-16 (IL-16). Therefore, the differentially expressed peptides in the five precursor protein domains may be potential bioactive peptides associated with α-syn and apoptosis. This study provides a validated peptidomics profile of SNCA-A30P mice and identifies potentially bioactive peptides linked to α-syn and apoptosis.

Surveillance of COVID-19 and influenza A(H1N1) prevalence in China via medicine-based wastewater biomarkers.

The simultaneous monitoring of individual or multiple diseases can be achieved by selecting therapeutic medicines used to treat the primary symptoms of the condition as biomarkers in wastewater. This study proposes a novel approach to monitor the prevalence of COVID-19 and influenza A (H1N1) by selecting nine medicines to serve as biomarkers, including three antipyretics, three antivirals, and three cough suppressants. To verify our approach, wastewater samples were collected from seventeen urban and five rural wastewater treatment plants (WWTPs) in a Chinese city over a period of one year. The use of antipyretics increased notably during the COVID-19 pandemic, while the consumption of antivirals for influenza A (H1N1) rose in the post-COVID-19 pandemic period, indicating a minor spike in the occurrence of influenza A (H1N1) after the COVID-19 pandemic. Fever is a significant symptom of COVID-19 and can serve as a reliable indicator of disease prevalence. Our research found that the prevalence of COVID-19 in urban areas was significantly higher (at 78.5 %, 95 % CI: 73.4 % - 83.9 %) than in rural areas (with a prevalence of 48.1 %, 95 % CI: 42.4 % - 53.8 %). The prevalence of COVID-19 in urban areas in this study was consistent with the data reported by the Chinese center for Disease Control and Prevention (82.4 %). Continuous monitoring of WWTPs in urban areas with fluctuating populations and complex demographics can provide early disease warning. Our results demonstrate the feasibility of evaluating community disease prevalence by selecting major therapeutic medicines as biomarkers in wastewater.

Deep carbon cycling during subduction revealed by coexisting diamond-methane-magnesite in peridotite.

Identification of multiphase inclusions in peridotite suggests that released carbon from a subducting slab can be stored as diamond+methane+magnesite in the overlying mantle wedge, achieving deep carbon cycling.

cdh23 affects congenital hearing loss through regulating purine metabolism.

Introduction: The pathogenic gene CDH23 plays a pivotal role in tip links, which is indispensable for mechanoelectrical transduction in the hair cells. However, the underlying molecular mechanism and signal regulatory networks that influence deafness is still largely unknown. Methods: In this study, a congenital deafness family, whole exome sequencing revealed a new mutation in the pathogenic gene CDH23, subsequently; the mutation has been validated using Sanger sequencing method. Then CRISPR/Cas9 technology was employed to knockout zebrafish cdh23 gene. Startle response experiment was used to compare with wide-type, the response to sound stimulation between wide-type and cdh23-/-. To further illustrate the molecular mechanisms underlying congenital deafness, comparative transcriptomic profiling and multiple bioinformatics analyses were performed. Results: The YO-PRO-1 assay result showed that in cdh23 deficient embryos, the YO-PRO-1 signal in inner ear and lateral line neuromast hair cells were completely lost. Startle response experiment showed that compared with wide-type, the response to sound stimulation decreased significantly in cdh23 mutant larvae. Comparative transcriptomic showed that the candidate genes such as atp1b2b and myof could affect hearing by regulating ATP production and purine metabolism in a synergetic way with cdh23. RT-qPCR results further confirmed the transcriptomics results. Further compensatory experiment showed that ATP treated cdh23-/- embryos can partially recover the mutant phenotype. Conclusion: In conclusion, our study may shed light on deciphering the principal mechanism and provide a potential therapeutic method for congenital hearing loss under the condition of CDH23 mutation.

Nickel-Catalyzed Reductive Decarboxylative/Deaminative Glycosylation of Activated Aliphatic Acids and Primary Amines.

This study describes the nickel-catalyzed reductive decarboxylative/deaminative glycosylation of activated aliphatic acids/amines. Various alkyl C-glycosides were efficiently constructed under simple and mild reaction conditions. The reactions were high-yielding and exhibited a broad substrate scope, thereby enabling the transformation of some structurally complex natural products and late-stage modifications of drugs.

Supercritical fluid in deep subduction zones as revealed by multiphase fluid inclusions in an ultrahigh-pressure metamorphic vein.

Due to their low viscosity, high mobility, and high element contents, supercritical fluids are important agents in the cycling of elements. However, the chemical composition of supercritical fluids in natural rocks is poorly understood. Here, we investigate well-preserved primary multiphase fluid inclusions (MFIs) from an ultrahigh-pressure (UHP) metamorphic vein of the Bixiling eclogite in Dabieshan, China, thus providing direct evidence for the components of supercritical fluid occurring in a natural system. Via the 3D modeling of MFIs by Raman scanning, we quantitatively determined the major composition of the fluid trapped in the MFIs. Combined with the peak-metamorphic pressure-temperature conditions and the cooccurrence of coesite, rutile, and garnet, we suggest that the trapped fluids in the MFIs represent supercritical fluids in a deep subduction zone. The strong mobility of the supercritical fluids with respect to carbon and sulfur suggests that such fluids have profound effects on global carbon and sulfur cycling.

Supporting Tremor Rehabilitation Using Optical See-Through Augmented Reality Technology.

Tremor is a movement disorder that significantly impacts an individual's physical stability and quality of life, and conventional medication or surgery often falls short in providing a cure. Rehabilitation training is, therefore, used as an auxiliary method to mitigate the exacerbation of individual tremors. Video-based rehabilitation training is a form of therapy that allows patients to exercise at home, reducing pressure on rehabilitation institutions' resources. However, it has limitations in directly guiding and monitoring patients' rehabilitation, leading to an ineffective training effect. This study proposes a low-cost rehabilitation training system that utilizes optical see-through augmented reality (AR) technology to enable tremor patients to conduct rehabilitation training at home. The system provides one-on-one demonstration, posture guidance, and training progress monitoring to achieve an optimal training effect. To assess the system's effectiveness, we conducted experiments comparing the movement magnitudes of individuals with tremors in the proposed AR environment and video environment, while also comparing them with standard demonstrators. Participants wore a tremor simulation device during uncontrollable limb tremors, with tremor frequency and amplitude calibrated to typical tremor standards. The results showed that participants' limb movement magnitudes in the AR environment were significantly higher than those in the video environment, approaching the movement magnitudes of the standard demonstrators. Hence, it can be inferred that individuals receiving tremor rehabilitation in the AR environment experience better movement quality than those in the video environment. Furthermore, participant experience surveys revealed that the AR environment not only provided a sense of comfort, relaxation, and enjoyment but also effectively guided them throughout the rehabilitation process.

Deaminative bromination, chlorination, and iodination of primary amines.

The primary amino group has been seldom utilized as a transformable functionality in organic synthesis. Reported herein is a deaminative halogenation of primary amines using N-anomeric amide as the nitrogen-deletion reagent. Both aliphatic and aromatic amines are competent substrates for direct halogenations. The mildness and robustness of the protocol are evidenced by the successful reactions of several complex- and functional group-enriched bioactive compounds or drugs. Elaboration of the resulting products provides interesting analogues of drug molecules.

Association between inflammatory bowel disease and periodontitis: A bidirectional two-sample Mendelian randomization study.

AIM: This Mendelian randomization (MR) study was performed to explore the potential bidirectional causal association between inflammatory bowel disease (IBD) and periodontitis. MATERIALS AND METHODS: We used genetic instruments from the genome-wide association study summary statistics of European descent for IBD (12,882 cases and 21,770 controls) to investigate the association with periodontitis (3046 cases and 195,395 controls) and vice versa. The radial inverse-variance weighted method was carried out to obtain the primary causal estimates, and the robustness of the results was assessed by a series of sensitivity analyses. Due to multiple testing, associations with p values <.008 were considered as statistically significant, and p values ≥.008 and <.05 were considered as suggestively significant. RESULTS: In the primary causal estimates, IBD as a whole was associated with an increased risk of periodontitis (odds ratio [OR], 1.060; 95% confidence interval [CI], 1.017; 1.105; p = .006). Subtype analyses showed that ulcerative colitis (UC) was associated with periodontitis (OR, 1.074; 95% CI 1.029; 1.122; p = .001), while Crohn's disease (CD) was not. Regarding the reverse direction, periodontitis showed a suggestive association with IBD as a whole (OR, 1.065; 95% CI 1.013; 1.119; p = .014). Subtype analyses revealed that periodontitis was associated with CD (OR, 1.100; 95% CI 1.038; 1.167; p = .001) but not UC. The final models after outlier removal showed no obvious pleiotropy, indicating that our primary analysis results were reliable. CONCLUSIONS: The present MR study provides moderate evidence on the bidirectional causal relationship between IBD and periodontitis. The bidirectional increased risk found in our study was marginal and, possibly, of limited clinical relevance. More studies are needed to support the findings of our current study.

Analysis of epidemic characteristics and related factors of norovirus in diarrhea patients in Guangxi, 2015-2020 / 中国热带医学

@#Abstract: Objective　To analyze the epidemiological characteristics and related factors of norovirus in Guangxi from 2015 to 2020, and to provide scientific recommendations for norovirus prevention and control. Methods The foodborne diseases surveillance data were collected from 11 sentinel hospitals through the National Foodborne Disease Monitoring and Reporting System from 2015 to 2020. R software with version 4.0.3 was used for descriptive and statistical analysis, including epidemic curve, chi-square test, and trend chi-square and so on. Logistic regression was used to analyze norovirus-related factors, OR values and 95% confidence intervals were calculated respectively with the statistical test level of P<0.05. Results There were 1 008 norovirus cases detected, with a detection rate of 12.75% (1 008/7 903). Children with age less than 5 years (OR=1.43, 95%CI: 1.13-1.82) and patients at age 20-45 (OR=1.45, 95%CI: 1.13-1.87) were high risk population. The detection rate was higher in autumn (OR=1.29, 95%CI: 1.08-1.53) but lower in summer (OR=0.67, 95%CI: 0.55-0.80). In addition, the tourist area (Guilin City) presented a higher detection rate than other areas (OR=1.41, 95%CI: 1.10-1.80). Aquatic products (OR=1.40, 95%CI: 1.03-1.91), meat and dairy products (OR=1.31, 95%CI: 1.06-1.61) were high-risk foods for norovirus infection. The prevention and control policies of COVID-19 can reduce the possibility of norovirus by 61% (OR=0.39, 95%CI: 0.31-0.49) showed a declining trend (Trend χ2=85.33, P<0.001). In addition, prolonged visit time can lead to 19%-23% decrease in the detection rate of norovirus (OR24-48 hours=0.81, 95%CI: 0.70-0.95; OR>48 hours=0.77, 95%CI: 0.63-0.93). Conclusions　The epidemic of norovirus presented seasonal and regional distribution in Guangxi with a declining detection rate trend in diarrhea patients during recent 6 years. Young children were high-risk population in infection norovirus. The intake of seafood can increase the risk of norovirus infection. The prevention and control policies of COVID-19 can sharply decrease the possibility of infection norovirus. The monitoring of key foods such as seafood should be strengthened, and the early screening of suspected cases should be taken. The norovirus monitoring should be improved to ensure the health of the population.

TREM2 knockdown improves the therapeutic effect of PD-1 blockade in hepatocellular carcinoma.

Triggering receptor expressed on myeloid cells 2 (TREM2), which is typically expressed in microglia/macrophage, is a crucial receptor modulating the activation of immune cells. Recent single-cell RNA sequencing studies of the tumor microenvironment (TME) have found that TREM2 is highly expressed in several subgroups of tumor-associated macrophages (TAMs) with immunosuppressive activity. TREM2 knockout mice are more resistant to tumor growth than wild-type mice in multiple mice tumor models. But the function of TREM2 expression in TAMs of hepatocellular carcinoma (HCC) is still unclear. Here we used a self-complementary adeno-associated virus (scAAV) with macrophage tropism to efficiently knockdown TREM2 in TAMs in vivo and found that the growth of hepatocellular carcinoma was suppressed by TREM2 knockdown. Moreover, we found that TREM2 knockdown remodeled TAMs to an immune-stimulating status and enhanced the therapeutic effect of PD-1 immune-checkpoint blockade in HCC.

Ileoanal Pouch Syndrome Is Common and Associated With Significant Disability in Patients With Ulcerative Colitis Undergoing IPAA.

BACKGROUND: Recently, ileoanal pouch syndrome (IPS) has been proposed and defined according to a series of patient-centered bowel symptoms and consequences after ileoanal pouch surgery. OBJECTIVE: The purpose of this study was to investigate the prevalence of IPS and the related disability in UC patients undergoing IPAA. DESIGN: This was a cross-sectional study. SETTING: This study was conducted in a tertiary center. PATIENTS: Data of 128 UC-related IPAA from October 2014 to May 2021 were collected. MAIN OUTCOME MEASURES: Primary outcomes were prevalence of IPS. RESULTS: One hundred twenty-eight patients were enrolled with a median postoperative follow-up of 2.64 (IQR, 1.31-3.80) years. The prevalence of IPS and its constituent symptoms and consequences are lower for patients with longer follow-up after ileostomy reversal. Fecal incontinence and pad usage had the greatest impact on the quality of life affecting 29% and 31% of patients. IPS group had a significantly higher IBD-Disability Index score compared to the non-IPS group (27.25 vs 12.15, p < 0.001). Multivariate analysis showed that 4 symptoms (fecal incontinence, clustering, fragmentation and incomplete evacuation, and nocturnal symptoms) and 2 consequences (pad usage and negative mental alterations) were associated with increased IBD-Disability Index (p < 0.05). For patients followed-up for >2 years, multivariate analysis showed that male gender (OR, 4.485; 95% CI, 1.354-14.857; p = 0.014), preoperative duration of disease (OR, 1.013; 95% CI, 1.001-1.025; p = 0.031), and postoperative follow-up (OR, 0.462; 95% CI, 0.244-0.876; p = 0.049) were independently associated with IPS. LIMITATIONS: This is a single-center cross-sectional study rather than a prospective multicenter large longitudinal study. CONCLUSIONS: IPS is a common situation negatively affecting the quality of life for patients with ulcerative colitis undergoing IPAA, and its rate decreased over time from ileal pouch surgery. See Video Abstract at http://links.lww.com/DCR/C41. EL SNDROME DEL RESERVORIO ILEOANAL ES COMN Y EST ASOCIADO CON UNA DISCAPACIDAD SIGNIFICATIVA EN PACIENTES CON CU CON RESERVORIO ILEAL Y ANASTOMOSIS RESERVORIOANAL: ANTECEDENTES:Recientemente se propuso y definió el síndrome del reservorio ileoanal de acuerdo con una serie de síntomas intestinales centrados en el paciente y las consecuencias después de la cirugía del reservorio ileoanal.OBJETIVO:El propósito de este estudio fue investigar la prevalencia del síndrome del reservorio ileoanal y la discapacidad relacionada en pacientes con colitis ulcerosa con reservorio ileal y anastomosis reservorio-anal.DISEÑO:Este fue un estudio transversal.ESCENARIO:Este estudio se realizó en un centro terciario.PACIENTES:Se recopilaron datos de 128 pacientes con reservorio ileal por colitis ulcerosa desde octubre de 2014 hasta mayo de 2021.PRINCIPALES MEDIDAS DE RESULTADO:Los resultados primarios fueron la prevalencia del síndrome del reservorio ileoanal.RESULTADOS:Ciento veintiocho pacientes fueron reclutados con una mediana de seguimiento postoperatorio de 2,64 (IQR, 1,31-3,80) años. La prevalencia del síndrome del reservorio ileoanal y sus síntomas y consecuencias constituyentes es menor para los pacientes con un seguimiento más prolongado después de la reversión de la ileostomía. La incontinencia fecal y el uso de compresas tuvieron el mayor impacto en la calidad de vida, afectando al 29% y al 31% de los pacientes. El grupo con síndrome del reservorio ileoanal tuvo una puntuación del índice de discapacidad por enfermedad inflamatoria intestinal significativamente más alta en comparación con el grupo sin síndrome del reservorio ileoanal (27,25 frente a 12,15, p <0,001). El análisis multivariado mostró que 4 síntomas (incontinencia fecal, agrupamiento, fragmentación y evacuación incompleta y síntomas nocturnos) y 2 consecuencias (uso de toallas higiénicas y alteraciones mentales negativas) se asociaron con un aumento del índice de discapacidad por enfermedad inflamatoria intestinal (p <0,05). Para los pacientes seguidos durante más de dos años, el análisis multivariado mostró que el sexo masculino (OR, 4,485; IC 95%, 1,354-14,857; p = 0,014), la duración preoperatoria de la enfermedad (OR, 1,013; IC 95%, 1,001-1,025; p = 0,031) y el seguimiento postoperatorio (OR, 0,462; IC 95%, 0,244-0,876; p = 0,049) se asociaron de forma independiente con el síndrome del reservorio ileoanal.LIMITACIONES:Este es un estudio transversal de un solo centro en lugar de un gran estudio longitudinal prospectivo multicéntrico.CONCLUSIONES:El síndrome del reservorio ileoanal es una situación común que afecta negativamente la calidad de vida de los pacientes con colitis ulcerosa sometidos a anastomosis del reservorio ileal-anal, y su tasa disminuyó con el tiempo a partir de la cirugía del reservorio ileal. El sexo masculino y la mayor duración preoperatoria de la enfermedad son factores de riesgo importantes para el síndrome del reservorio ileoanal. Consulte Video Resumen en http://links.lww.com/DCR/C41. (Traducción-Dr. Felipe Bellolio).

Regiocontrolled allylic functionalization of internal alkene via selenium-π-acid catalysis guided by boron substitution.

The selenium-π-acid-catalysis has received increasing attention as a powerful tool for olefin functionalization, but the regioselectivity is often problematic. Reported herein is a selenium-catalyzed regiocontrolled olefin transpositional chlorination and imidation reaction. The reaction outcome benefits from an allylic B(MIDA) substitution. And the stabilization of α-anion from a hemilabile B(MIDA) moiety was believed to be the key factor for selectivity. Broad substrate scope, good functional group tolerance and generally good yields were observed. The formed products were demonstrated to be valuable precursors for the synthesis of a wide variety of structurally complex organoborons.

Assessment of correlations between sildenafil use and comorbidities and lifestyle factors using wastewater-based epidemiology.

Sildenafil (SIL) is widely used to treat erectile dysfunction. Information on its consumption and the factors influencing its use is limited in China. In this study, we sampled composite influent wastewater samples from 33 Chinese cities and analyzed SIL using liquid chromatography-tandem mass spectrometry. SIL consumption was estimated using wastewater-based epidemiology (WBE) and ranged from 10.6 mg/d/1000 people to 132 mg/d/1000 people, with a mean of 53 mg/d/1000 people. Prescription sales (3570 kg) accounted for 13.3% of the estimated SIL use (26842 kg) in 2018, thereby implying that SIL illicit use was greater than prescription use in China. Some regional differences were observed in SIL use, which was significantly higher in North China than South China (p < 0.05), thereby reflecting that the prevalence of SIL was affected by differences in lifestyle and socioeconomic factors. We found significant positive correlations between SIL use and consumption of allopurinol, hydrochlorothiazide, nicotine, and alcohol, thereby suggesting that the prevalence of SIL was associated with the prevalence of gout, hypertension, smoking, and drinking. Moreover, age structures, internet use, and marriage rates were positively correlated with SIL use, whereas the unemployment rate was negatively correlated with SIL use. Our study demonstrates that WBE is valuable for medical research to investigate licit and illicit drug use and to assess the underlying associations of different chemical uses.

Hypervalent iodine-mediated ß-difluoroalkylboron synthesis via an unusual 1,2-hydrogen shift enabled by boron substitution.

ß-Difluoroalkylborons, featuring functionally important CF2 moiety and synthetically valuable boron group, have great synthetic potential while remaining synthetically challenging. Herein we report a hypervalent iodine-mediated oxidative gem-difluorination strategy to realize the construction of gem-difluorinated alkylborons via an unusual 1,2-hydrogen migration event, in which the (N-methyliminodiacetyl) boronate (BMIDA) motif is responsible for the high regio- and chemoselectivity. The protocol provides facile access to a broad range of ß-difluoroalkylborons under rather mild conditions. The value of these products was demonstrated by further transformations of the boryl group into other valuable functional groups, providing a wide range of difluorine-containing molecules.

Silencing of Nudix type 5 represses proliferation and invasion and enhances chemosensitivity of gastric carcinoma cells by affecting the AKT/GSK-3ß/ß-catenin pathway.

Nudix type 5 (NUDT5) has been recently identified as a new cancer-associated protein that is involved in numerous cancers. To date, the relationship between NUDT5 and gastric carcinoma has not been addressed. In the current research, we focused on exploring the potential relevance of NUDT5 in gastric carcinoma. The initial analysis of NUDT5 expression in gastric carcinoma by TCGA data revealed a clear increase in NUDT5 expression in tumor versus normal tissue. The increased expression of NUDT5 was also validated in the clinical specimens of gastric carcinoma by immunoblotting detection. Moreover, high NUDT5 levels predicted a poorer overall survival in gastric carcinoma patients. A series of cellular functional assays demonstrated that gastric carcinoma cells with silenced NUDT5 exhibited decreased proliferative and invasive ability, increased cell cycle arrest at the G0/G1 phase, and enhanced chemosensitivity. In-depth research showed that the silencing of NUDT5 led to a reduction in the activation of AKT and ß-catenin. The reactivation of AKT blocked the repressive effect of NUDT5 silencing on ß-catenin activation. The forced expression of ß-catenin also reversed NUDT5-silencing-mediated anticancer effects. A Xenograft tumor assay confirmed the anticancer role of NUDT5 in gastric carcinoma in vivo. In short, these findings reveal elevated NUDT5 levels in gastric carcinoma and demonstrate that the inhibition of NUDT5 displays promising anticancer effects by affecting the AKT/ß-catenin pathway. Thus, our work unveils a vital role of NUDT5 in gastric carcinoma and indicates it as a viable candidate target for anticancer drug discovery.