KCNH6 is essential for insulin secretion by regulating intracellular ER Ca2+ store.

Appropriate Ca2+ concentration in the endoplasmic reticulum (ER), modulating cytosolic Ca2+ signal, serves significant roles in physiological function of pancreatic ß cells. To maintaining ER homeostasis, Ca2+ movement across the ER membrane is always accompanied by a simultaneous K+ flux in the opposite direction. KCNH6 was proven to modulate insulin secretion by controlling plasma membrane action potential duration and intracellular Ca2+ influx. Meanwhile, the specific function of KCNH6 in pancreatic ß-cells remains unclear. In this study, we found that KCNH6 exhibited mainly ER localization and Kcnh6 ß-cell-specific knockout (ßKO) mice suffered from abnormal glucose tolerance and impaired insulin secretion in adulthood. ER Ca2+ store was overloaded in islets of ßKO mice, which contributed to ER stress and ER stress-induced apoptosis in ß cells. Next, we verified that ethanol treatment induced increases in ER Ca2+ store and apoptosis in pancreatic ß cells, whereas adenovirus-mediated KCNH6 overexpression in islets attenuated ethanol-induced ER stress and apoptosis. In addition, tail-vein injections of KCNH6 lentivirus rescued KCNH6 expression in ßKO mice, restored ER Ca2+ overload and attenuated ER stress in ß cells, which further confirms that KCNH6 protects islets from ER stress and apoptosis. These data suggest that KCNH6 on the ER membrane may help to stabilize intracellular ER Ca2+ stores and protect ß cells from ER stress and apoptosis. In conclusion, our study reveals the protective potential of KCNH6-targeting drugs in ER stress-induced diabetes.

TERRA regulates DNA G-quadruplex formation and ATRX recruitment to chromatin.

The genome consists of non-B-DNA structures such as G-quadruplexes (G4) that are involved in the regulation of genome stability and transcription. Telomeric-repeat containing RNA (TERRA) is capable of folding into G-quadruplex and interacting with chromatin remodeler ATRX. Here we show that TERRA modulates ATRX occupancy on repetitive sequences and over genes, and maintains DNA G-quadruplex structures at TERRA target and non-target sites in mouse embryonic stem cells. TERRA prevents ATRX from binding to subtelomeric regions and represses H3K9me3 formation. G4 ChIP-seq reveals that G4 abundance decreases at accessible chromatin regions, particularly at transcription start sites (TSS) after TERRA depletion; such G4 reduction at TSS is associated with elevated ATRX occupancy and differentially expressed genes. Loss of ATRX alleviates the effect of gene repression caused by TERRA depletion. Immunostaining analyses demonstrate that knockdown of TERRA diminishes DNA G4 signals, whereas silencing ATRX elevates G4 formation. Our results uncover an epigenetic regulation by TERRA that sequesters ATRX and preserves DNA G4 structures.

High bicarbonate concentration increases glucose-induced insulin secretion in pancreatic ß-cells.

Low serum bicarbonate is closely related to type 2 diabetes mellitus. However, the precise role of bicarbonate on glucose homeostasis and insulin secretion remains unknown. In this study, we investigated the effects of bicarbonate concentration on pancreatic ß-cells. It was observed that the high bicarbonate concentration of the cell culture medium significantly increased the glucose-induced insulin secretion (GSIS) levels in mouse islets, MIN6, and the INS-1E ß cells. MIN6 cells presented an impaired GSIS; the cells produced a lower bicarbonate concentration when co-cultured with Capan-1 than when with CFPAC-1. NBCe1, a major bicarbonate transporter was observed to block the increasing insulin secretions, which were promoted by a high concentration of bicarbonate. In addition, higher extracellular bicarbonate concentration significantly increased the intracellular cAMP level, pHi, and calcium concentration with a 16.7 mM of glucose stimulation. Further study demonstrated that a low concentration of extracellular bicarbonate significantly impaired the functioning of pancreatic ß cells by reducing coupling Ca2+ influx, whose process may be modulated by NBCe1. Taken together, our results conclude that bicarbonate may serve as a novel target in diabetes prevention-related research.

Association Between Peripheral Eosinophilia and Clinical Characteristics of Adult-onset Still's Disease with Persistent Eruption: A Retrospective Study.

Persistent eruption occurs in a subset of patients with adult-onset Still's disease. In our experience, a considerable proportion of these patients present with peripheral eosinophilia. The aims of this study were to summarize the clinical and histological features of patients with adult-onset Still's disease with persistent eruption in the current study cohort, and to assess the association between peripheral eosinophil levels and disease characteristics. A total of 21 patients with adult-onset Still's disease with persistent eruption were included in this retrospective study. Koebner signs, an important diagnostic clue, were found in 85.7% of patients. The proportion of patients presenting with eosinophilia within the disease course was 57.1%. Skin histology revealed infiltration of eosinophils in 90.5% of patients. Peripheral eosinophil levels were positively associated with involved body surface area. Patients with normal peripheral eosinophil counts were more likely to achieve complete remission than those with abnormal peripheral eosinophil counts. Eosinophils may be involved in the pathogenesis of skin eruption. Abnormal peripheral eosinophil counts in these patients may indicate a more refractory disease course.

Nitrogen-doped carbon quantum dots-decorated 2D graphitic carbon nitride as a promising photocatalyst for environmental remediation: A study on the importance of hybridization approach.

Growing concerns of water pollution by dye pollutants from the textile industry has led to vast research interest to find green solutions to address this issue. In recent years, heterogeneous photocatalysis has harvested tremendous attention from researchers due to its powerful potential applications in tackling many important energy and environmental challenges at a global level. To fully utilise the broad spectrum of solar energy has been a common aim in the photocatalyst industry. This study focuses on the development of an efficient, highly thermal and chemical stable, environmentally friendly and metal-free graphitic carbon nitride (g-C3N4) to overcome the problem of fast charge recombination which hinders photocatalytic performances. Nitrogen-doped carbon quantum dots (NCQDs) known for its high electronic and optical functionality properties is believed to achieve photocatalytic enhancement by efficient charge separation through forming heterogeneous interfaces. Hence, the current work focuses on the hybridisation of NCQDs and g-C3N4 to produce a composite photocatalyst for methylene blue (MB) degradation under LED light irradiation. The optimal hybridisation method and the mass loading required for maximum attainable MB degradation were systematically investigated. The optimum photocatalyst, 1 wt% NCQD/g-C3N4 composite was shown to exhibit a 2.6-fold increase in photocatalytic activity over bare g-C3N4. Moreover, the optimum sample displayed excellent stability and durability after three consecutive degradation cycles, retaining 91.2% of its original efficiency. Scavenging tests were also performed where reactive species, photon-hole (h+) was identified as the primary active species initiating the pollutant degradation mechanism. The findings of this study successfully shed light on the hybridisation methods of NCQDs which improve existing g-C3N4 photocatalyst systems for environmental remediation by utilising solar energy.

[Chest High-resolution Computed Tomography Imaging Features of Lung Involvement in Rheumatoid Arthritis].

Objective To explore the chest high-resolution computed tomography (HRCT) features in patients with rheumatoid arthritis (RA) complicated with pulmonary involvement. Methods Totally 161 patients with RA with lung involvement were collected from June 2014 to May 2018. The chest HRCT findings were retrospectively analyzed. According to the imaging features as well as the results of history taking,pulmonary function test,pathology,and bronchoalveolar lavage fluid test,RA-related lung diseases (RA-LD) were classified and their clinical characteristics were compared. Results These 161 RA-LD patients (56 males and 105 females) whose mean age at diagnosis was (60.7±12.8) years (14-85 years) included 87 cases of usual interstitial pneumonia (UIP) (including 16 cases of possible UIP),44 cases of non-specific interstitial pneumonia (NSIP),10 cases of organizing pneumonia,7 cases of lymphocytic interstitial pneumonia,9 cases of small airway disease (SAD) (including 8 cases of bronchiolitis obliterans and 1 case of follicular bronchiolitis),and 4 other lung manifestations (including 3 cases of diffuse alveolar hemorrhage and 1 case of rheumatoid nodules). The UIP group had the oldest average age [(63.3±12.1) years old] and the highest smoking rate (41.4%). The SAD group had the youngest average age [(54.7±15.1) years old] and there was no smoking history. There were significant differences between these two groups (P=0.020,P<0.001). Seventy patients (43.5%) with RA-LD were complicated with pleural lesions. Conclusions RA involving the lung is common and has varied imaging manifestations,with interstitial lung diseases (mainly UIP and NSIP) being the most important manifestations. RA patients should undergo lung HRCT as early as possible to identify the lung involvement and related types.

The renal manifestations of type 4 familial partial lipodystrophy: a case report and review of literature.

BACKGROUND: Lipodystrophy syndromes are rare disorders of variable body fat loss associated with potentially serious metabolic complications. Familial partial lipodystrophy (FPLD) is mostly inherited as an autosomal dominant disorder. Renal involvement has only been reported in a limited number of cases of FPLD. Herein, we present a rare case of proteinuria associated with type 4 FPLD, which is characterized by a heterozygous mutation in PLIN1 and has not been reported with renal involvement until now. CASE PRESENTATION: A 15-year-old girl presented with insulin resistance, hypertriglyceridaemia, hepatic steatosis and proteinuria. Her glucose and glycated haemoglobin levels were within normal laboratory reference ranges. A novel heterozygous frameshift mutation in PLIN1 was identified in the patient and her mother. The kidney biopsy showed glomerular enlargement and focal segmental glomerulosclerosis under light microscopy; the electron microscopy results fit with segmental thickening of the glomerular basement membrane. Treatment with an angiotensin-converting enzyme inhibitor (ACEI) decreased 24-h protein excretion. CONCLUSIONS: We report the first case of proteinuria and renal biopsy in a patient with FPLD4. Gene analysis demonstrated a novel heterozygous frameshift mutation in PLIN1 in this patient and her mother. Treatment with ACEI proved to be beneficial.

Multi-phase distribution and comprehensive ecological risk assessment of heavy metal pollutants in a river affected by acid mine drainage.

To date, there is a lack of a comprehensive research on heavy metals detection and ecological risk assessment in river water, sediments, pore water (PW) and suspended solids (SS). Here, the concentrations of heavy metals, including Cu, Zn, Mn, Cd, Pb and As, and their distribution between the four phases was studied. Samples for analysis were taken from twelve sites of the Hengshi River, Guangdong Province, China, during the rainy and dry seasons. A new comprehensive ecological risk index (CERI) based on considering metal contents, pollution indices, toxicity coefficients and water categories is offered for prediction of potential risk on aquatic organisms. The results of comprehensive analysis showed that the highest concentrations of Cu, Zn and Mn of 6.42, 87.17 and 98.74mg/L, respectively, in PW were comparable with those in water, while concentrations of Cd, Pb and As of 609.5, 2757 and 96.38µg/L, respectively, were 2-5 times higher. The sum of the exchangeable and carbonate fractions of target metals in sediments followed the order of Cd > Mn > Zn > Pb > Cu > As. The distribution of heavy metals in phases followed the order of sediment > SS > water > PW, having the sum content in water and PW lower than 2% of total. The elevated ecological risk for a single metal and the phase were 34,585 for Cd and 1160 for water, respectively, implied Cd as a priority pollutant in the considered area. According to the CERI, the maximum risk value of 769.3 was smaller than 1160 in water, but higher than those in other phases. Out of considering the water categories and contribution coefficients, the CERI was proved to be more reliable for assessing the pollution of rivers with heavy metals. These results imply that the CERI has a potential of adequate assessment of multi-phase composite metals pollution.

Effect of injury-curing cataplasma on expression of AQP3 in skeletal muscles of rats by regulating cAMP-PKA signal pathway.

Curing-injury Cataplasma to promote regulatory mechanism of acute closed soft tissue injury swelling of rats may be related to inhibit PGE2, regulating the cAMP - PKA signaling pathways, high expression of AQP - 3. SD rats. 48 rats randomly divided into three groups, each group of 16. Blank group: only hair removal treatment, marking the scope, not building; Control group: marking the depilation area shall be made within the scope of acute closed soft tissue injury model of rats, don't give medication; Experimental group: building local injury Papua gels, a fixed tape. Building after 1 d, 3 d, 7 d, 14 d four phase randomly put to death in the rat 4, only partial muscle tissue specimens after using Western Blot to detect AQP - 3 protein expression level, enzyme-linked immunoassay detection PGE2, cAMP, the expression of PKA, parallel correlation analysis. In 3 d, 7 d, 14 d three time points, AQP-3 and PKA of Experimental group on the expression is higher than the Control group (P<0.01), the expression of PGE2 and cAMP is lower than the Control group (P<0.01); And Experimental group, Control group and Blank group differences were statistically significant (P<0.05). Acute closed soft tissue Curing-injury Cataplasma to promote a swelling, may be related to inhibit PGE2, regulating the cAMP - PKA signaling pathways, high expression of AQP - 3.

Distribution and migration of heavy metals in soil and crops affected by acid mine drainage: Public health implications in Guangdong Province, China.

Acid mine drainages (AMD) contain high concentrations of heavy metals, and their discharges into streams and rivers constitute serious environmental problems. This article examines the effects of AMD on soil, plant and human health at Dabaoshan mine in Guangdong Province, China. Although the large scale mining was stopped in 2011, the heavy metal pollution in soil continues to endanger crops and human health in that region. The objectives of this study were to elucidate distribution and migration of Cd, Cu, Zn, As and Pb and associated health implications to local inhabitants. We collected and analyzed 74 crop samples including 28 sugarcane, 30 vegetables, 16 paddy rice and the corresponding soil samples, used correlation and linear relationship for transformation process analysis, and applied carcinogenic and non-carcinogenic risk for hazard evaluation. Results showed that the local soils were heavily polluted with Cd, Cu and As (especially for Cd) and the mean Igeo value was as high as 3.77. Cadmium, Cu, and Zn in rice and vegetables were comparable with those found four years ago, while As and Pb in edible parts were 2 to 5 times lower than before. The root uptake of Cd and Zn contributed mainly to their high concentrations in crops due to high exchangeable fraction of soil, while leafy vegetables accumulated elevated As and Pb contents mainly due to the atmospheric deposition. Metal concentrations in sugarcane roots were higher than those in rice and vegetable roots. The risk assessment for crops consumption showed that the hazard quotients values were of 21 to 25 times higher than the threshold level for vegetables and rice, indicating a potential non-carcinogenic risk to the consumers. The estimated mean total cancer risk value of 0.0516 more than 100 times exceeded the USEPA accepted risk level of 1×10(-4), indicating unsuitability of the soil for cultivating the food crops. Therefore, the local agricultural and the land-use policies need to be reevaluated.

Simultaneous Determination of Eight Alkaloids in Rat Plasma by UHPLC-MS/MS after Oral Administration of Coptis deltoidea C. Y. Cheng et Hsiao and Coptis chinensis Franch.

A ultra-high performance liquid chromatography-electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS) method was successfully developed and validated for the identification and determination of eight alkaloids: tetrahydropalmatine (A); palmatine (B); magnoflorine (C); columbamine (D); berberine (E); worenine (F); berberrubine (G) and coptisine (H) in rat plasma, which are the active components in Coptis deltoidea C. Y. cheng et Hsiao (CCY) and Coptis chinensis Franch (CF). The chromatographic separation of analytes was successfully achieved on an Agilent SB-C18 column (1.8 µm, 150 mm × 2.1 mm) using a programme with a mobile phase consisting of acetonitrile and water containing 0.3% acetic acid at a flow rate of 0.25 mL/min. The analytes were detected with a triple quadrupole tandem MS in multiple reaction monitoring (MRM) mode and an electrospray ionization (ESI) source in positive mode. The validated method showed good linearity over a wide concentration range (r² > 0.991), and lower limits of quantification (LLOQ) less than 1.1 ng/mL for all analytes, and matrix effects ranged from 85.2% to 106.8%. The mean extraction recoveries were no less than 86.4%, and the precision and accuracy were within the acceptable limits. All analytes were proven to be stable during sample storage and analysis procedures. The method validation results demonstrated that the proposed method was sensitive, specific, and reliable, which could lay a foundation for the pharmacokinetic study of eight analytes after oral administration of CCY and CF in subsequent studies.

Gas-phase lithium cation affinity of glycine.

The gas-phase lithium cation binding thermochemistry of glycine has been determined theoretically by quantum chemical calculations at the G4 level and experimentally by the extended kinetic method using electrospray ionization quadrupole time-of-flight tandem mass spectrometry. The lithium cation affinity of glycine, ∆(Li)H°(298)(GLY), i.e. the∆(Li)H°(298) of the reaction GlyLi(+)→ Gly + Li(+)) given by the G4 method is equal to 241.4 kJ.mol(-1) if only the most stable conformer of glycine is considered or to 242.3 kJ.mol(-1) if the 298K equilibrium mixture of neutral conformers is included in the calculation. The ∆(Li)H°(298)(GLY) deduced from the extended kinetic method is obviously dependent on the choice of the Li(+) affinity scale, thus∆(Li)H°(298)(GLY) is equal to 228.7±0.9(2.0) kJ.mol(- 1) if anchored to the recently re-evaluated lithium cation affinity scale but shifted to 235.4±1.0 kJ.mol(-1) if G4 computed lithium cation affinities of the reference molecules is used. This difference of 6.3 kJ.mol(-1) may originate from a compression of the experimental lithium affinity scale in the high ∆(Li)H°(298) region. The entropy change associated with the reaction GlyLi(+)→Gly + Li(+) reveals a gain of approximately 15 J.mol(-) 1.K(-1) with respect to monodentate Li(+) acceptors. The origin of this excess entropy is attributed to the bidentate interaction between the Li(+) cation and both the carbonyl oxygen and the nitrogen atoms of glycine. The computed G4 Gibbs free energy,∆(Li)G°(298)(GLY) is equal to 205.3 kJ.mol(-1), a similar result, 201.0±3.4 kJ.mol(-1), is obtained from the experiment if the∆(Li)G°(298) of the reference molecules is anchored on the G4 results.

A methodology for evaluating the relative pollution level of metal pollution in surface sediments of rivers based on the statistical results of relevant literatures covering world-wide rivers.

Due to the intervention of human activities, the background values of riverbed sediment exhibit spatiotemporal variability, which can affect the accuracy of risk assessment results. Using risk assessment that do not rely on background values is an executable alternative to avoid such problems. In this study, a relative pollution level assessment (RPLA) method which was based on the statistical results of relevant literatures was proposed. This method includes a four-step data processing procedure to extract the evaluation indexes of relative pollution degree of pollutants in environment and a series of relative pollution status assessment methods to evaluate the overall relative pollution level and regional difference of world-wide rivers. To demonstrate how to use RPLA method, 310 relevant literatures covering world-wide rivers were selected. And the ambient background value (x̅), the world-wide threshold values (WWTV) and the relative pollution grades (LEVEL I ∼ IV) of 9 target metals (Cr, Ni, Cu, Zn, As, Cd, Pb, Sb and Tl) in riverbed surface sediments of world-wide rivers were extracted and used for evaluation. Moreover, the stability and applicability of RPLA method were evaluated. Results show that the evaluation results of RPLA method are robust and comparable with traditional evaluation method.

Leaching behavior and kinetics of beryllium in beryllium-containing sludge (BCS).

Beryllium-containing sludge (BCS) is a byproduct of the physicochemical treatment of beryllium smelting wastewater. The pollutant element beryllium within BCS is highly unstable and extremely toxic, characterized by its small ionic radius and low charge density, resulting in a high risk of leaching and migration. This study is the first to investigate the leaching behavior, influencing mechanisms, and kinetic processes of beryllium in BCS under various environmental conditions. The results indicate that, under national standard conditions, beryllium exhibits a rapid leaching phase within the first 5 h, which then stabilizes after 10 h, with the total leached content significantly exceeding the leaching toxicity identification standards. Under mildly acidic (pH ≤ 5) or highly alkaline (pH = 14) conditions, beryllium demonstrates pronounced leaching and migration behaviors. Notably, in acidic conditions, the leaching rate exceeds 80% within 5 h. Combining the treatment process of beryllium-containing wastewater with analytical methods such as SEM, XPS, ToF-SIMS, and FTIR, it is revealed that due to the heterogeneous nature of BCS, the particle aggregates dissociate over time under acidic conditions. The particle surfaces become increasingly rough, leading to dissolution and the emergence of more reactive sites, resulting in a high proportion of beryllium leaching. Under these conditions, the gradual reaction of Be(OH)2 in BCS to form soluble Be2+ and its hydrolytic complexes is identified as the primary mechanism for extensive beryllium migration. The process encounters minimal diffusion resistance and is classified as reaction-controlled. In acidic conditions with pH = 4, the leaching rate of beryllium significantly increases with rising temperature. The leaching kinetics equation is [(1-x)-0.44]=e(18.26-53050RT)·t, with an apparent activation energy of 53.05 kJ mol-1.

Tandem Mass Tag-Based Proteomic Analysis of Normal and Degenerated Human Intervertebral Discs.

Background: Intervertebral disc degeneration (IVDD) is the main cause of low back pain (LBP), but the specific regulatory factors, pathways and specific molecular mechanisms remain unclear. Methods: We identified and quantitatively analyzed Pfirrmann Grade II (n=3) and Pfirrmann Grade IV (n=3) pulposus samples via MRI. The differential abundance of proteins in the samples was determined and quantitatively analyzed by relative and absolute quantitative analysis of the isotope marker levels combined with the liquid chromatography-tandem mass spectrometry (LC‒MSMS/MS). Results: A total of 70 proteins (30 significantly increased proteins (> 1.2-fold change) and 40 significantly decreased proteins (< 0.8-fold change)) showed different levels among the groups. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology (GO) enrichment analyses and Western blot analysis showed that CYCS, RAC1, and PSMD14 may play important roles in IVDD and that Epstein‒Barr virus infection, viral myocarditis, colorectal cancer, nonalcoholic fatty liver disease (NAFLD) and amyotrophic lateral sclerosis (ALS) are the main pathways involved in IVDD. Conclusion: CYCS, RAC1 and PSMD14 may play important roles in IVDD, and Epstein‒Barr virus infection, viral myocarditis, colorectal cancer, NAFLD and ALS may be the main pathways involved in IVDD.

Sleep quality, psychological resilience, family resilience, social support, and mental disability in patients with chronic schizophrenia: A cross-sectional study.

After the remission of psychotic symptoms in patients with chronic schizophrenia, a persistently high rate of disability suggests potential influences from socio-ecological factors. This study aimed to explore the complex relationships between socioecological factors, including sleep quality, psychological resilience, family resilience, and social support, and the severity of psychiatric disability in patients with chronic schizophrenia. Employing a cross-sectional design, the study involved 188 individuals with chronic schizophrenia. Disability was measured using the World Health Organization Disability Assessment Schedule 2.0 (WHO-DAS 2.0), while social support, family resilience, psychological resilience, and sleep quality were assessed using the Social Support Rating Scale (SSRS), Family Hardiness Index (FHI), Connor-Davidson Resilience Scale (CD-RISC), and Pittsburgh Sleep Quality Index (PSQI), respectively. LASSO regression and structural equation modeling (SEM) analyses were conducted to identify predictive factors and their interrelationships. The mean WHO-DAS 2.0 score of 72.91 ± 14.04 indicated substantial difficulties in daily activities, necessitating comprehensive support among participants. LASSO regression identified frequent disease relapses, low education levels, and poor sleep quality as risk factors for disability, whereas strong social support, family resilience, and individual resilience emerged as protective factors against disability. SEM demonstrated that the enhancement of family and individual resilience by social support contributes to the mitigation of disability. The study underscores the critical roles of social support, family resilience, and individual psychological resilience in reducing disability in patients with chronic schizophrenia, suggesting that interventions targeting these factors may improve rehabilitation outcomes.

All-potassium channel CRISPR screening reveals a lysine-specific pathway of insulin secretion.

OBJECTIVE: Genome-scale CRISPR-Cas9 knockout coupled with single-cell RNA sequencing (scRNA-seq) has been used to identify function-related genes. However, this method may knock out too many genes, leading to low efficiency in finding genes of interest. Insulin secretion is controlled by several electrophysiological events, including fluxes of KATP depolarization and K+ repolarization. It is well known that glucose stimulates insulin secretion from pancreatic ß-cells, mainly via the KATP depolarization channel, but whether other nutrients directly regulate the repolarization K+ channel to promote insulin secretion is unknown. METHODS: We used a system involving CRISPR-Cas9-mediated knockout of all 83 K+ channels and scRNA-seq in a pancreatic ß cell line to identify genes associated with insulin secretion. RESULTS: The expression levels of insulin genes were significantly increased after all-K+ channel knockout. Furthermore, Kcnb1 and Kcnh6 were the two most important repolarization K+ channels for the increase in high-glucose-dependent insulin secretion that occurred upon application of specific inhibitors of the channels. Kcnh6 currents, but not Kcnb1 currents, were reduced by one of the amino acids, lysine, in both transfected cells, primary cells and mice with ß-cell-specific deletion of Kcnh6. CONCLUSIONS: Our function-related CRISPR screen with scRNA-seq identifies Kcnh6 as a lysine-specific channel.

[Effect of acrylic bone cement mixed with calcium sulfate combined with percutaneous kyphoplasty in the treatment of osteoporotic fractures].

OBJECTIVE: To investigate the clinical efficacy of acrylic cement (PMMA) mixed with calcium sulfate combined with percutaneous kyphoplasty (PKP) in the treatment of osteoporotic fracture (OVCF). METHODS: The clinical data of 191 patients with OVCF treated with PKP from January 2020 to March 2021 were retrospectively analyzed. Among them, 82 patients with 94 vertebral bodies were treated with PMMA mixed with calcium sulfate as the observation group, and 109 patients with 125 vertebral bodies were treated with pure PMMA as the control group. Among the 82 patients in the observation group, there were 16 males and 66 females, with a mean age of (75.35±11.22) years old, including 36 thoracic vertebrae and 58 lumbar vertebrae. In the control group, there were 109 patients, 22 males and 87 females, with an average age of (74.51±9.21) years old, including 63 thoracic vertebrae and 62 lumbar vertebrae. The visual analog scale (VAS) before operation and 1 day, 3 months and 1 year after operation were calculated. The Oswestry disability index (ODI), Cobb's angle, vertebral body height and the probability of postoperative bone cement leakage were used to analyze the efficacy of the two groups. RESULTS: All the patients were followed up for more than one year. Compared with the control group, there was no significant difference in operation time, bleeding volume and bone cement injection volume between the two groups(P>0.05), while the leakage rate of bone cement was significantly lower in the observation group (P<0.05). In addition, there was no significant difference in VAS, ODI, Cobb angle, and vertebral body height between the two groups before operation, and 1 day, 3 months, and 1 year after operation (P>0.05), but each index was improved compared with that before operation (P<0.05). CONCLUSION: PMMA mixed with calcium sulfate has equivalent efficacy in treating OVCF than PMMA alone, but can effectively reduce the probability of cement leakage.

[Clinical study of double plate system in the treatment of complex proximal humeral fractures in the elderly].

OBJECTIVE: To explore the clinical outcomes of anteromedial combined with lateral locking plate for complex proximal humeral fractures in the eldery. METHODS: From June 2018 to October 2020, 30 patients who underwent surgical treatment for Neer grade 3 to 4 proximal humeral fractures, including 8 males and 22 females, aged from 51 to 78 years old with an average of (61.5±7.5) years old. Of them, 15 patients had fractures fixed with anteromedial combined with lateral locking plate(ALLP group), whereas 15 received internal fixation with proximal humerus locking plate only(PHLP group). The clinical data, simple shoulder test (SST), humeral head height loss, varus angle and shoulder range of motion were compared between the two groups. RESULTS: All fractures were healed. The follow-up time ranged from 12 to 24 months, with an average of(14.3±2.9) months. The operation time of ALLP group was longer than that of PHLP group (P<0.05). There was no significant difference in intraoperative blood loss between the two groups (P>0.05). There was no significant difference in SST score between the two groups at 1, 3 and 12 months after operation (P>0.05). In terms of radiographic measurement, there was no significant difference in humeral head height loss and varus angle between the two groups at 1 and 3 months after operation (P>0.05). At 12 months after operation, the height loss and varus angle of humeral head in ALLP group were lower than those in PHLP group (P<0.05). In shoulder range of motion, the range of forward elevation in ALLP group was larger than that in PHLP group 1 year after operation(P<0.05). There was no significant difference in external rotation between the two groups. CONCLUSION: Anteromedial combined with lateral locking plate in the treatment of complex proximal humeral fractures in the elderly can increase the stability of the medial column and obtain a good fracture prognosis. But there are also disadvantages such as longer operation time, so it should be individualized according to the fracture type of the patient.

Toxic metals and the risks of sludge from the treatment of wastewater from beryllium smelting.

The release of highly toxic beryllium in sludge (BCS) produced by physico-chemical treatment of beryllium-containing wastewater from Be smelting production has become a growing concern with the widespread use of Be in the defense industry. This work investigated the potential mobility of Be in BCS. The toxicity characteristic leaching procedure (TCLP) of BCS showed that the amount of leached Be was up to 202 mg L-1, which exceeded the regulated limit by nearly 10,000 times. The chemical fractionation analysis further revealed that the excessive amount of Be leached from BCS was contributed to the high content of acid-soluble fraction and reducible fraction of Be, which accounted for over 70% of the Be content. The results obtained from mineralogical automatic analyzer (MLA) showed that gypsum (23.23%) and epidote (19.55%) were the two major mineralogical phases of BCS. Both were small and loosely structured agglomerated particles with a D50 of 6.61 µm and 3.31 µm. ToF-SIMS results revealed that the Be distribution on the surface of BCS particles was relatively dispersed, with no aggregation or encapsulation. Be co-precipitated with gypsum and chlorite in the form of unstable Be(OH)2, which attached to the surface of these small particles. The unstable state of Be and the small size, loose structure and high liberation of the host material phases are the main reasons for the high leaching mobility of Be. The results of the risk assessment indicated that BCS posed an extremely high potential ecological risk, with Be being the most significant contributor.