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Cloperastine is a pivotal antibechic widely prescribed to treat cough caused by respiratory diseases. The present trial evaluated the pharmacokinetics (PK), bioequivalence (BE) and safety effects of the generic test (T) tablet of cloperastine after single-dose administration of cloperastine, compared with the original reference (R) tablet of cloperastine.The purpose of this trial was to compare the PK, BE and safety of a test 10 mg versus the reference 10 mg formulation of cloperastine under fasting and postprandial conditions in healthy Chinese volunteers.A single-centre, randomised, open, double-cycle, self-crossover, single oral administration Phase I trial was performed in healthy Chinese volunteers. A total of 60 subjects were enrolled in either the fasting (28 subjects) or the postprandial condition (32 subjects). Subjects randomly received a single dose of the T or R preparation (10 mg dose). Plasma concentrations of cloperastine were analysed by a validated LC-MS/MS method. The primary endpoints of the PK parameters were the area under the plasma concentration-time curve from zero to 72 h (AUCA total of 25 and 30 subjects in the fasting and postprandial conditions completed this clinical trial, respectively. The geometric mean ratio (GMR) of the T/R for the CThe T and R preparations were bioequivalent under both conditions. Food has no significant effect on the absorption of cloperastine. Moreover, T and R preparations were well tolerated. The trial registration number (TRN) and date of registrations were CTR20212515, 13 October 2021.

The hot deformation of TA15 titanium alloy was studied by the hot compression test on the Gleeble-3800 thermal simulation equipment. The true stress-strain curves of TA15 titanium alloy at the temperature of 1123-1223K and the strain rate of 0.001-1s-1 were obtained.. The results show that the flow stress increases with decreasing temperature, and increases as the strain rate increases. And the deformation process is accompanied by work hardening and dynamic recovery and dynamic recrystallization. Based on the true stress-strain curves of TA15 titanium alloy, the Arrhenius-typed constitutive equation was established. The thermal deformation activation energy of TA15 titanium alloy with a strain of 0.2 is 746.27kJ/mol.

Given the afferent functions, sensory nerves recently have been found exerting efferent influences and directly alter organ physiology. Moreover, studies have demonstrated the crucial role of sensory nerves in the physiological function of osteoclasts. However, the direct evidence of whether sensory nerve efferent influences osteoclast, remains lacking. Here, we found abundant efferent signals transported from sensory nerves into osteoclasts; sensory hypersensitivity significantly increased osteoclastic bone resorption; and sensory neurons (SN) directly promote osteoclastogenesis in vitro co-culture system. Then our screening identified a novel neuropeptide Cyp40, is the efferent signal from the sensory nerve and plays a critical role in the osteoclastogenesis, via aryl hydrocarbon receptor (AhR)-Ras/Raf-pErk-NFATc1 pathway. These findings revealed a novel mechanism of sensory nerves on bone regulation: the direct promotion of osteoclastogenesis by secreting Cyp40. Inhibiting the Cyp40 could therefore be a strategy to improve bone quality in osteoporosis and promote bone repair after bone injury.

The sedimentation performance of sludge affects the operation of the entire treatment process. It is important to measure the zone settling velocity accuracy and high efficiency which can reflect the sedimentation performance of sludge. Traditional methods often rely entirely on manual implementation. Long hours of manual measurement work brings physical strain to the operator, low efficiency of the entire measurement work and a large error in the measurement results. Therefore, the method combining image processing and neural network to realize automatic recognition of the scale value of sludge water interface in sludge sedimentation video is proposed. Based on the recognized scale value, overall sedimentation change curve is drew, and the sludge sedimentation rate is calculated. Then, the activated sludge was examined by phase contrast microscope to obtain sludge image. The flocs, filamentous bacteria and other targets in the image are segmented with Labelme, the characteristics of flocs and sedimentation rate of the previous day are taken as input of deep stochastic configuration network, and the calculated sludge sedimentation rate is output for predicting layered sedimentation rate. Through experimental analysis, the prediction error is within a reasonable range. The intelligent prediction of sludge regional sedimentation velocity is realized.

To endow Ti-based orthopedic implants immunomodulatory capability and thus enhanced osseointegration, different amounts of Sr are doped in Na2TiO3 nanorods in the arrays with identical nanotopographic parameters (rod diameter, length and inter-rod spacing) by substitution of Na+ using hydrothermal treatment. The obtained arrays are denoted as STSr2, STSr4, and STSr7, where the arabic numbers indicate the incorporating amounts of Sr in Na2TiO3. The modulation effects of the Sr-doped nanorods arrays on macrophage polarization and osteogenetic functions of osteoblasts are investigated, together with the array without Sr (ST). Moreover, osseointegration of these arrays are also assayed in rat femoral condyles. Sr-doped nanorods arrays accelerate M1 (pro-inflammatory phenotype)-to-M2 (anti-inflammatory phenotype) transformation of the adhered macrophages, enhancing secretion of pro-osteogenetic cytokines and growth factors (TGF-β1 and BMP2), moreover, the Sr doped arrays directly enhance osteogenetic functions of osteoblasts. The enhancement of paracrine of M2 macrophages and osteogenetic function of osteoblasts is promoted with the increase of Sr incorporating amounts. Consequently, Sr doped arrays show significantly enhanced osseointegration in vivo compared to ST, and STSr7 exhibits the best performance. Our work sheds a new light on the design of surface chemical components and structures for orthopedic implants to enhance their osseointegration.

An elderly Chinese male patient was diagnosed with compound heterozygous spinocerebellar ataxia type 8; molecular diagnosis found that the (CTA)n(CTG)n repeat unit of his ATXN8/ATXN8OS gene was 134/93. The patient has a 6-year medical history, mainly manifested by ataxia, dysarthria, abnormal eye movements, and pyramidal signs. Magnetic resonance imaging (MRI) showed no obvious abnormalities in the medulla oblongata and cervical spinal cord except for cerebellar atrophy and sulci enlargement. There are heterozygous SCA8 individuals among his family members, but there are significant differences in their onset age and clinical manifestations.This case reminds us that (CTA)n(CTG)n repeats are very prone to dynamic mutations in intergenerational inheritance, and the ATXN8/ATXN8OS gene penetrance is different in different SCA8 individuals, which suggests that genetic detection is of great importance.

Using nucleophilic, boron-based –CF2Ar reagents, we demonstrate three methods to form C–CF bonds: (1) nucleophilic aromatic substitution, (2) palladium catalyzed cross-coupling, and (3) nucleophilic substitution.

Malignant hyperthermia (MH) is an autosomal dominant genetic condition of the skeletal muscle triggered by inhaled general anesthetic agents or succinylcholine and associated with a hypermetabolic state and skeletal muscle rigidity. Tachycardia, increased carbon dioxide production, hypercarbia, hyperthermia, acidosis, hyperkalemia, cardiac arrhythmias, muscle rigidity, and rhabdomyolysis are common symptoms of MH. As the progression of the syndrome could be rapid or less evident, even experienced physicians have difficulty in diagnosing MH, which can lead to delays in treatment and increased mortality. We report a rare case of a 36-year-old man, who underwent open reduction and internal fixation of the left clavicle after inhaled anesthetics. The patient developed dyspnea, hypotension, unremitting hyperthermia, tachycardia, and elevated serum myoglobin, and finally died of pyemia and disseminated intravascular coagulation. We reviewed the process of disease development, summarized the steps of diagnosis, and improved genetic testing. Exome sequencing revealed a new mutation c.8519G>A (p.arg2840 GLN) in the RYR1 gene that could be associated with MH. The gene mutation was also found in his daughter’s genetic test. This case emphasized the importance of the awareness of MH and its atypical clinical symptoms. The presence of dyspnea, hypotension, unremitting hyperthermia, tachycardia, and raised myoglobin in serum might further strengthen the clinical diagnosis of suspected MH.

SARS-CoV-2, which likely spilled over from wildlife, is the third highly pathogenic human coronavirus. Being highly transmissible, it is perpetuating a pandemic and continuously posing a severe threat to global public health.

We outline a new synthetic method to prepare mono- and polyfluoroepoxides from a diverse pool of electrophiles (ketones, acyl chlorides, esters) and fluoroalkyl anion equivalents. The initially formed α-fluoro alkoxides undergo subsequent intramolecular ring closure when heated. We demonstrated the versatility of the method through the isolation of 16 mono- and polyfluoroepoxide products. These compounds provide unique entry points for further diversification via either fluoride migration coupled with ring opening, or defluorinative functionalization reactions, the latter of which can be used as a late-stage method to install select bioactive moieties. The reaction sequences described herein provide a pathway to functionalize the commonly observed products formed from 1,2-addition into carbonyl electrophiles.

Stroke is a fatal neurological disease, which seriously threatens human health and life. Ischemic stroke (IS) is the most common type of stroke in clinic. Its pathogenesis is very complex, mainly caused by nerve damage caused by brain blood supply disorder. Previous studies have confirmed that natural products play important roles in improving neurological disorders. Furthermore, our previous results also suggested that Shenxiong Tongmai granule, a clinically used herbal medicines’ prescription, has a good ameliorating effect on IS. In the present study, we found that Monomethyl lithospermate (MOL), a constituent of Shenxiong Tongmai granule, significantly improved the neurological damage in middle cerebral artery occlusion (MCAO) rats. MOL can significantly improve the neurological deficit score of MCAO rats, and improve the damage of hippocampal neurons caused by ischemia-reperfusion (IR). At the same time, we also found that MOL could reduce the level of oxidative stress in the brain tissues of MCAO rats. Furthermore, the oxygen and glucose deprivation/Reoxygenation (OGD/R)-induced SHSY-5Y cell model was established in vitro to investigate the pharmacological activity and molecular mechanisms of MOL in improving the nerve injury of IS rats. The results showed that MOL could increase the cell viability of SHSY-5Y cells, inhibit the mitochondrial membrane potential (MMOP) collapse and suppress apoptosis. In addition, MOL also ameliorated the elevated oxidative stress level caused by OGR/R treatment in SHSY-5Y cells. Further mechanistic studies showed that MOL could activate the PI3K/AKT pathway via promoting the phosphorylation of PI3K and AKT in MCAO rats and OGR/R-induced SHSY-5Y cells, which could be partially blocked by addition of PI3K/AKT pathway inhibitor of LY294002. Taken together, our current study suggested that MOL exerts a protective effect against neural damage caused by IS in vivo and in vitro by activating the PI3K/AKT pathway.

The worldwide pandemic of coronavirus disease 2019 (COVID-19) presents us with a serious public health crisis. To combat the virus and slow its spread, wider testing is essential. There is a need for more sensitive, specific, and convenient detection methods of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Advanced detection can greatly improve the ability and accuracy of the clinical diagnosis of COVID-19, which is conducive to the early suitable treatment and supports precise prophylaxis. In this article, we combine and present the latest laboratory diagnostic technologies and methods for SARS-CoV-2 to identify the technical characteristics, considerations, biosafety requirements, common problems with testing and interpretation of results, and coping strategies of commonly used testing methods. We highlight the gaps in current diagnostic capacity and propose potential solutions to provide cutting-edge technical support to achieve a more precise diagnosis, treatment, and prevention of COVID-19 and to overcome the difficulties with the normalization of epidemic prevention and control.

Lysosomes play key roles in different cellular processes such as autophagy, phagocytosis, and apoptosis. Lysosomal dysfunction is related to many diseases. Fluorescence lysosome staining strategy is valuable for the researches on the lysosome involvement in different pathological diagnosis. Here we describe fluorescence lysosome staining methods with carbon dots for the identification of lysosomes in living and fixed cells.

Purpose: To analyze the distribution of fibrovascular proliferative membrane (FVPM) in proliferative diabetic retinopathy (PDR) patients that need treated with pars plana vitrectomy (PPV), and to evaluate the outcomes separately. Methods: Retrospective review of consecutive 25-G PPV cases operated for PDR between September 2018 and April 2020. All FVPMs were outlined and assigned to three groups: arcade type, juxtapapillary type and central type. General characteristics, operation-related variables, best-corrected visual acuity (BCVA) 12 month postoperative and complications were recorded. , All patients were followed up for over one year Results: In total, 93 eyes were recruited. Among them, the FVPMs distribution of nasotemporal and inferiosuperioral were significantly different (both p < 0.01), with 87 (93.55%) FVPMs located in the nasal hemispheres, and 67 (72.04%) in the inferior hemispheres. The eyes with a central FVPM required the longest operation time, with silicon oil used in most patients, generally combined with tractional retinal detachment (RD) and rhegmatogenous RD, as well as the worst postoperative best-corrected visual acuity and the highest rates of recurrent RD and iatrogenic retinal break formation (all p < 0.05). Conclusion: FVPMs were more commonly found in the nasal and inferior mid-peripheral retina in addition to the area of arcade vessels. Performing 25-G PPV for treating PDR eyes with a central FVPM had a relatively worse prognosis.

The activation of ferroptosis is a new effective way to treat drug-resistant solid tumors. Ferroptosis is an iron-mediated form of cell death caused by the accumulation of lipid peroxides. The intracellular imbalance between oxidant and antioxidant due to the abnormal expression of multiple redox active enzymes will promote the produce of reactive oxygen species (ROS). So far, a few pathways and regulators have been discovered to regulate ferroptosis. In particular, the cystine/glutamate antiporter (System Xc−), glutathione peroxidase 4 (GPX4) and glutathione (GSH) (System Xc−/GSH/GPX4 axis) plays a key role in preventing lipid peroxidation-mediated ferroptosis, because of which could be inhibited by blocking System Xc−/GSH/GPX4 axis. This review aims to present the current understanding of the mechanism of ferroptosis based on the System Xc−/GSH/GPX4 axis in the treatment of drug-resistant solid tumors.

The purpose of this trial was to evaluate the pharmacokinetics (PK), bioequivalence (BE), and safety of 2 preparations of hydroxychloroquine (200-mg tablet) under fasting and fed conditions. A total of 180 subjects (fasting condition: n = 80; fed condition: n = 100) were randomly enrolled in this randomized, open, single-dose, single-cycle parallel phase Ⅰ clinical study. Under the 2 conditions, the subjects were randomly administered the test (T) or reference (R) tablet, both at a dose of 200 mg (1 tablet). Liquid chromatography-tandem mass spectrometry was used to determine the concentration of hydroxychloroquine in healthy subjects after oral administration of the T or R preparation to evaluate the PK characteristics. In this trial, the T and R preparations of hydroxychloroquine were bioequivalent under both conditions within the range of 80%-125%. No serious adverse events (SAEs) were found in the safety assessments for either condition, and all adverse events (AEs) were mild, except for 2 moderate AEs in the fed condition, indicating good safety.