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Objectives Fluoxetine has been used as the first line for the therapy of depression. However, lack of therapeutic efficacy and time lag still limit the application of fluoxetine. Gap junction dysfunction is a potentially novel pathogenic mechanism for depression. To clarify the mechanism underlying these limitations, we investigated whether gap junction was related to the antidepressant effects of fluoxetine. Methods and key findings After chronic unpredictable stress (CUS), animals showed decreases in gap junction intracellular communication (GJIC). Treatment with fluoxetine 10 mg/kg significantly improved GJIC and anhedonia of rats until six days. These results indicated that fluoxetine improved gap junction indirectly. Furthermore, to test the role of gap junction on antidepressant effects of fluoxetine, we blocked gap junction using carbenoxolone (CBX) infusion in the prefrontal cortex. CBX dampened fluoxetine-induced decrease in immobility time of mice in tail suspension test (TST). Conclusions Our study suggested that gap junction dysfunction blocks antidepressant effects of fluoxetine, contributing to understanding the mechanism underlying the time lag of fluoxetine.

Doxorubicin hydrochloride (DOX) is one of the widely used antineoplastic agents in treating various cancers, yet it is always associated with the occurrence of adverse reactions that limit its clinical use. Currently, encapsulating DOX in micelles may represent a promising strategy to reduce toxicity and side effects of the drug. This study aimed to explore a novel acitretin-based surfactant (ACMeNa) with good solid stability to encapsulate DOX to form micelles (ACM-DOX). In this work, ACM-DOX micelles were prepared by a microfluidic method free of organic solvents. The characteristics of ACM-DOX micelles were assessed, including morphology, particle size, stability, entrapment efficiency, and drug loading. An in vitro cytotoxicity experiment of the micelles on MDA-MB-231 (a human breast cancer cell line) was also performed. The micelle formation mechanism suggested that the insoluble ACMeNa/DOX complex was formed by electrostatic interaction, and subsequently encapsulated by self-assembly into micelles. The designed ACM-DOX micelles had an average particle size of 19.4 ± 0.2 nm and a zeta potential of −43.7 ± 2.4 mV, with entrapment efficiency and drug loading efficiency of 92.4 ± 0.5% and 33.4 ± 0.3%, respectively. The ACM-DOX micelles had worm-like structures under a Cryo-transmission electron microscope and exhibited good stability within 8 hours after reconstitution and 4- to 32-fold dilution of its reconstituted solution. ACM-DOX micelles released 80% of DOX within 24 hours in a medium of pH = 5.0, and its drug profile can be described by a first-order model. Moreover, ACM-DOX micelles showed cytotoxicity against MDA-MB-231 in a dose-dependent manner, and displayed a higher antitumor activity as compared with free DOX, with IC50 values of DOX and ACM-DOX micelles being 6.80 ± 0.50 and 4.64 ± 0.32 μg/mL, respectively. Given above, ACMeNa has great application potential as a DOX carrier for the treatment of cancers.

A new cyclohexenone derivative, phomopine (1), together with five known compounds (2-6) were isolated from Phomopsis sp. XM-01. The structure of 1 was determined by extensive spectroscopic analyses and electronic circular dichroism (ECD) calculation. In vitro bioassays, compounds 1 and 2 exhibited potent antimicrobial activities against Candida albicans and Staphylococcus aureus with their corresponding minimum inhibitory concentrations (MICs) of 64 μg/mL and 16 μg/mL, respectively.

Three-dimensional printing (3DP) has high flexibility and controllability, and has attracted extensive attention in the biomedical field. However, the scaffolds prepared only by 3D bioprinting have poor mechanical properties, and they cannot effectively carry the required drugs. At the same time, compared with the size of cells, the pore size of 3D printed scaffolds is relatively large, and the efficiency of cell inoculation and tissue formation are still limited by the pore resolution of scaffolds. Therefore, a new method of forming 3D printing trachea composites is proposed. When combined, 3D bioprinting and electrospinning (ESP) can overcome the issues associated with scaffolds prepared by 3D bioprinting alone. Nanofibers create a suitable environment for cell growth. In terms of material use, Polycaprolactone (PCL) is commonly used as an ideal material source for 3D printing, but its biomechanical properties are insufficient. Cellulose nanocrystals (CNC) can effectively improve the properties of polymers such as PCL. Therefore, the inner layer of the scaffold used in tracheal surgery is created from PCL/CNC composite by 3D bioprinting, and the outer nano-cellulose film is deposited on the inner surface by electrospinning. Mechanical properties and cell adhesion/growth of scaffolds prepared by 3D bioprinting combined with electrospinning were found to be superior to those of scaffolds prepared by 3D bioprinting.

Adhesion G protein-coupled receptors (aGPCRs) constitute an evolutionarily ancient family of receptors that often undergo autoproteolysis to produce α and β subunits

Breast neuroendocrine neoplasms (NENs) constitute a rare histologic subtype that includes both neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs). In this study, we aimed to gain insight into the clinical and molecular characteristics of NENs of the breast. NEN and paired distant normal fresh tissues and clinicopathological data were obtained from 17 patients with NENs, and clinicopathological data were collected from 755 patients with invasive breast carcinomas of no special type (IBCs-NST). We compared the clinicopathological characteristics of NENs and IBCs-NST and performed whole-exome sequencing (WES) of both NEN and paired normal tissues. Compared with the IBC-NST patients, the NEN patients had a higher mean age, lower clinical stage, and lower pathological nodal (pN) stage (P

One of the most popular edible mushrooms in the world, Flammulina velutipes, has been shown to possess pharmacological properties such as anti-inflammatory and antioxidant properties. However, the potential activity of the brown strain of F. velutipes, a hybrid between the white and yellow strains, has not been thoroughly investigated. Numerous studies have been conducted in recent years to determine whether natural products can aid in improving or treating kidney diseases. In this study, we focused on the renoprotective effects of the brown strain of F. velutipes on cisplatin-induced acute kidney injury (AKI) in mice. Mice were pretreated with water extract from the brown strain of F. velutipes (WFV) from day 1 to day 10, with a single-dose intraperitoneal injection of cisplatin on day 7 to induce AKI. Our results demonstrated that WFV administration resulted in a reduction in weight loss and the amelioration of renal function and renal histological changes in mice with cisplatin-induced AKI. WFV improved antioxidative stress and anti-inflammatory capacity by increasing antioxidant enzymes and decreasing inflammatory factors. The expression of related proteins was determined via Western blot analysis, which showed that WFV could improve the expression of apoptosis and autophagy. We used the PI3K inhibitor Wortmannin and found that WFV achieved a protective effect by modulating the PI3K/AKT pathway and the expression of autophagy. Overall, WFV as a natural substance could be used as a new therapeutic agent for AKI.

BACKGROUND: The validation of various risk scores in elderly patients with comorbid atrial fibrillation (AF) and acute coronary syndrome (ACS) has not been reported. The present study compared the predictive performance of existing risk scores in these patients. METHODS: A total of 1252 elderly patients with AF and ACS comorbidities (≥ 65 years old) were consecutively enrolled from January 2015 to December 2019. All patients were followed up for one year. The predictive performance of risk scores in predicting bleeding and thromboembolic events was calculated and compared. RESULTS: During the 1-year follow-up, 183 (14.6%) patients had thromboembolic events, 198 (15.8%) patients had BARC class ≥ 2 bleeding events, and 61 (4.9%) patients had BARC class ≥ 3 bleeding events. For the BARC class ≥ 3 bleeding events, discrimination of the existing risk scores was low to moderate, PRECISE-DAPT (C-statistic: 0.638, 95% CI: 0.611-0.665), ATRIA (C-statistic: 0.615, 95% CI: 0.587-0.642), PARIS-MB (C-statistic: 0.612, 95% CI: 0.584-0.639), HAS-BLED (C-statistic: 0.597, 95% CI: 0.569-0.624) and CRUSADE (C-statistic: 0.595, 95% CI: 0.567-0.622). However, the calibration was good. PRECISE-DAPT showed a higher integrated discrimination improvement (IDI) than PARIS-MB, HAS-BLED, ATRIA, and CRUSADE (P < 0.05) and the best decision curve analysis (DCA). For thromboembolic events, the discrimination of GRACE (C-statistic: 0.636, 95% CI: 0.608-0.662) was higher than CHA2DS2-VASc (C-statistic: 0.612, 95% CI: 0.584-0.639), OPT-CAD (C-statistic: 0.602, 95% CI: 0.574-0.629) and PARIS-CTE (C-statistic: 0.595, 95% CI: 0.567-0.622). The calibration was good. Compared to OPT-CAD and PARIS-CTE, the IDI of the GRACE score slightly improved (P < 0.05). However, NRI analysis showed no significant difference. DCA showed that the clinical practicability of thromboembolic risk scores was similar. CONCLUSIONS: The discrimination and calibration of existing risk scores in predicting 1-year thromboembolic and bleeding events were unsatisfactory in elderly patients with comorbid AF and ACS. PRECISE-DAPT showed higher IDI and DCA than other risk scores in predicting BARC class ≥ 3 bleeding events. The GRACE score showed a slight advantage in predicting thrombotic events.

Purpose This paper aims to investigate the effect of characteristic parameters of pits on the mechanical properties and fracture model of cable steel wires. Design/methodology/approach The tensile test and finite element analysis of steel wires with corrosion damage were carried out. The stress development of corroded steel wire under corrosion morphology was studied by the 3D reverse reconstruction technology. The internal relationship between the stress triaxiality, equivalent plastic strain and pit depth, depth-width ratio of corroded steel wire was discussed. Findings With the increase of corrosion degree, the neck shrinkage phenomenon of steel wire was not significant, and the crack originated near the pit bottom and expanded to the section inside of specimen. The fiber area of corroded steel wire decreased while the radiation area increased, and the ductile fracture gradually changed to brittle fracture. The pit size significantly changed the triaxial degree and distribution of stress and accelerated the initiation and propagation of internal cracks at the neck shrinkage stage. Originality/value The proposed fracture model based on the void growth model could accurately simulate the fracture behavior of steel wires with corrosion damage.

Purpose The role of circulating tumor cells (CTCs) in hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is not fully understood. Methods In this retrospective analysis, we included 316 HCC patients who underwent hepatectomy and preoperative CTC detection. We selected 41 pairs of matched HCC patients with and without PVTT using propensity score matching (PSM) analysis. We compared the preoperative CTC counts in patients from both the full cohort and the PSM model. We also analyzed their associations with disease-free survival (DFS) and overall survival (OS). Results Before and after PSM analysis, the preoperative CTC counts in the HCC with PVTT group were substantially higher than in the HCC without PVTT group. In both the full cohort of patients and the PSM model, patients with CTC ≥ 2 had significantly shorter OS and DFS than patients with CTC Conclusion We discovered a link between preoperative CTC counts and the occurrence of PVTT and confirmed the prognostic significance of preoperative CTC in HCC patients with PVTT. These findings suggest that preoperative CTC counts have the potential to assist in identifying patients with HCC and PVTT who may benefit from surgery.

IntroductionAlzheimer’s disease (AD) is characterized by increasing cognitive dysfunction, progressive cerebral amyloid beta (Aβ) deposition, and neurofibrillary tangle aggregation. However, the molecular mechanisms of AD pathologies have not been completely understood. As synaptic glycoprotein neuroplastin 65 (NP65) is related with synaptic plasticity and complex molecular events underlying learning and memory, we hypothesized that NP65 would be involved in cognitive dysfunction and Aβ plaque formation of AD. For this purpose, we examined the role of NP65 in the transgenic amyloid precursor protein (APP)/presenilin 1 (PS1) mouse model of AD.MethodsNeuroplastin 65-knockout (NP65–/–) mice crossed with APP/PS1 mice to get the NP65-deficient APP/PS1 mice. In the present study, a separate cohort of NP65-deficient APP/PS1 mice were used. First, the cognitive behaviors of NP65-deficient APP/PS1 mice were assessed. Then, Aβ plaque burden and Aβ levels in NP65-deficient APP/PS1 mice were measured by immunostaining and western blot as well as ELISA. Thirdly, immunostaining and western blot were used to evaluate the glial response and neuroinflammation. Finally, protein levels of 5-hydroxytryptamin (serotonin) receptor 3A and synaptic proteins and neurons were measured.ResultsWe found that loss of NP65 alleviated the cognitive deficits of APP/PS1 mice. In addition, Aβ plaque burden and Aβ levels were significantly reduced in NP65-deficient APP/PS1 mice compared with control animals. NP65-loss in APP/PS1 mice resulted in a decrease in glial activation and the levels of pro- and anti-inflammatory cytokines (IL-1β, TNF-α, and IL-4) as well as protective matrix YM-1 and Arg-1, but had no effect on microglial phenotype. Moreover, NP65 deficiency significantly reversed the increase in 5-hydroxytryptamine (serotonin) receptor 3A (Htr3A) expression levels in the hippocampus of APP/PS1 mice.DiscussionThese findings identify a previously unrecognized role of NP65 in cognitive deficits and Aβ formation of APP/PS1 mice, and suggest that NP65 may serve as a potential therapeutic target for AD.

BackgroundWhile the association between physical activity (PA) and depression has been established, there is limited research on the effect of PA on the risk of depression among Chinese individuals. Thus, this study aimed to investigate the relationship between PA and depression among Chinese individuals.MethodsWe used a stratified random sampling approach to recruit participants from five urban districts in Wuhan, China. A total of 5,583 permanent residents aged 18 years or older completed questionnaires, which included the International Physical Activity Questionnaire Short Form (IPAQ-SF) to measure PA, and the 9-item Patient Health Questionnaire (PHQ-9) to evaluate depressive symptoms. To control for potential confounders, multiple logistic regression was employed to assess the association of PA with depression.ResultsThe depression group had significantly lower weekly PA levels, measured in metabolic equivalent of task-minutes per week (MET-min/w), compared to the non-depression group [1,770 (693–4,200) MET-min/w vs. 2,772 (1,324–4,893) MET-min/w, p P for interaction = 0.019).ConclusionThe findings suggest a negative association between PA and risk of depressive symptoms, indicating that moderate to high levels of PA may serve as a protective factor against depressive symptoms.

BackgroundToxoplasmosis caused by Toxoplasma gondii is a globally distributed zoonosis. Most infections appear asymptomatic in immunocompetent individuals, but toxoplasmosis can be fatal in fetuses and immunocompromised adults. There is an urgent need to research and develop effective and low-toxicity anti-T. gondii drugs because of some defects in current clinical anti-T. gondii drugs, such as limited efficacy, serious side effects and drug resistance.MethodsIn this study, 152 autophagy related compounds were evaluated as anti-T. gondii drugs. The activity of β-galactosidase assay based on luminescence was used to determine the inhibitory effect on parasite growth. At the same time, MTS assay was used to further detect the effects of compounds with over 60% inhibition rate on host cell viability. The invasion, intracellular proliferation, egress and gliding abilities of T. gondii were tested to assess the inhibitory effect of the chosen drugs on the distinct steps of the T. gondii lysis cycle.ResultsThe results showed that a total of 38 compounds inhibited parasite growth by more than 60%. After excluding the compounds affecting host cell activity, CGI-1746 and JH-II-127 were considered for drug reuse and further characterized. Both CGI-1746 and JH-II-127 inhibited tachyzoite growth by 60%, with IC50 values of 14.58 ± 1.52 and 5.88 ± 0.23 μM, respectively. TD50 values were 154.20 ± 20.15 and 76.39 ± 14.32 μM, respectively. Further research found that these two compounds significantly inhibited the intracellular proliferation of tachyzoites. Summarize the results, we demonstrated that CGI-1746 inhibited the invasion, egress and especially the gliding abilities of parasites, which is essential for the successful invasion of host cells, while JH-II-127 did not affect the invasion and gliding ability, but seriously damaged the morphology of mitochondria which may be related to the damage of mitochondrial electron transport chain.DiscussionTaken together, these findings suggest that both CGI-1746 and JH-II-127 could be potentially repurposed as anti-T. gondii drugs, lays the groundwork for future therapeutic strategies.

Door-to-balloon (DTB) time significantly affects the prognosis of patients with ST-segment elevation myocardial infarction (STEMI). The effects of temporal differences in emergency department (ED) arrival time on DTB time and on different segments of DTB time remain inconclusive. Therefore, we performed a retrospective study in a tertiary hospital between January 2013 and December 2021 and investigated the relationship between a patient’s arrival time and both their DTB time and different segments of their DTB time. Of 732 STEMI patients, 327 arrived during the daytime (08:01–16:00), 268 during the evening (16:01–24:00), and 137 at night (00:01–08:00). Significantly higher odds of delay in DTB time were observed during the nighttime (adjusted odds ratio (aOR): 2.87; 95% confidence interval (CI): 1.50–5.51, p = 0.002) than during the daytime. This delay was mainly attributed to a delay in cardiac catheterization laboratory (cath lab) activation-to-arrival time (aOR: 6.25; 95% CI: 3.75–10.40, p < 0.001), particularly during the 00:00–04:00 time range. Age, sex, triage level, and whether patients arrived during the COVID-19 pandemic also had independent effects on different segments of DTB time. Further studies are required to investigate the root causes of delay in DTB time and to develop specific strategies for improvement.

Nitrate allocation in Arabidopsis (Arabidopsis thaliana) represents an important mechanism for mediating plant environmental adaptation. However, whether this mechanism occurs or has any physiological/agronomic importance in the ammoniphilic plant rice (Oriza sativa L.) remains unknown. Here, we address this question through functional characterization of the Nitrate transporter 1/Peptide transporter Family (NPF) transporter gene OsNPF7.9. Ectopic expression of OsNPF7.9 in Xenopus oocytes revealed that the gene encodes a low-affinity nitrate transporter. Histochemical and in-situ hybridization assays showed that OsNPF7.9 expresses preferentially in xylem parenchyma cells of vasculature tissues. Transient expression assays indicated that OsNPF7.9 localizes to the plasma membrane. Nitrate allocation from roots to shoots was essentially decreased in osnpf7.9 mutants. Biomass, grain yield, and nitrogen use efficiency (NUE) decreased in the mutant dependent on nitrate availability. Further analysis demonstrated that nitrate allocation mediated by OsNPF7.9 is essential for balancing rice growth and stress tolerance. Moreover, our research identified an indica–japonica divergent single-nucleotide polymorphism occurring in the coding region of OsNPF7.9, which correlates with enhanced nitrate allocation to shoots of indica rice, revealing that divergent nitrate allocation might represent an important component contributing to the divergent NUE between indica and japonica subspecies and was likely selected as a favorable trait during rice breeding.

Oviductal extracellular vesicles (OEVs) play an important role in fertilization and embryo development. However, it remains largely unknown whether the size and protein cargo of OEVs change during the estrous cycle in mice. This study analyzed the changes in the size distribution and protein cargo of OEVs at four stages of the estrous cycle in mice. The distribution widths of OEVs according to the estrous cycle stage were as follows: proestrus, 20–690 nm in diameter, with two peaks at 50 and 250 nm; estrus, 22–420 nm in diameter, with two peaks at 40 and 200 nm; metestrus, 30–70 nm diameter, with a single peak at 40 nm; and diestrus, 10–26 nm diameter, with a single peak at 20 nm. The estrogen receptor (ER) level in OEVs at the proestrus stage differed significantly from that at estrus (P = 0.013) and diestrus (P = 0.005). The levels of CD9 and Hsc70 fluctuated across the four stages, although with no significant differences. Furthermore, OEVs were observed among the cilia and microvilli of epithelial cells at the proestrus, estrus, and diestrus stages, but not at the metestrus stage. The number of observed OEVs was the highest at the proestrus stage, followed by the estrus, and the diestrus stage. Endosomes were also observed at the estrus and diestrus stages. The change of the OEV size and ER cargo is associated with the estrous cycle in mice. Our findings increase the understanding of the physiological characteristics of OEVs, which may have clinical applications.

A facile strategy was developed for the preparation of magnetically recyclable Co2P nanosheets with efficient catalytic activity for NaBH4 hydrolysis.

AIM: To compare the change of refractive power and corneal high-order aberrations after femtosecond laser-assisted excimer laser in situ keratomileusis(FS-LASIK)and FS-LASIK combined with accelerated corneal cross-linking(FS-LASIK Xtra)for high myopia correction, and to evaluate the early effects of two surgical methods to correct high myopia. METHODS:Retrospective case-control study. Totally 42 patients(84 eyes)with high myopia underwent FS-LASIK Xtra and FS-LASIK in our hospital from April 2019 to April 2020 were followed up for 3mo, including 21 patients in each group(42 eyes). The uncorrected visual acuity(UCVA), spherical equivalent(SE), astigmatism and corneal high-order aberration of the two groups were analyzed and compared.RESULTS: The UCVA of the FS-LASIK Xtra group was significantly lower than that of the FS-LASIK group at 1d after surgery(P0.05). The postoperative SE of the two groups was significantly lower than that before surgery, at 3mo after surgery, 38 eyes(90%)in the FS-LASIK Xtra group and 41 eyes(98%)in the FS-LASIK group had SE within ±1.00D. In both groups, 35 eyes(83%)had residual astigmatism within 0.50D after surgery. The total corneal high-order aberrations, spherical aberrations, coma and clover aberrations in the two groups were increased at 3mo after surgery, the total high-order aberration and clover aberration in the FS-LASIK Xtra group were greater than those in the FS-LASIK group(all P

Jasmine virus H (JaVH) is a newly reported viral pathogen of jasmine in China and USA. To study the viral gene function and pathogenic mechanism, a full-length infectious clone of JaVH (pXT-JaVHFJ) was constructed under the control of the cauliflower mosaic virus 35S promoter. pXT-JaVHFJ induced a systemic infection in Nicotiana benthamiana plants by Agro-infiltration, which demonstrated that pXT-JaVHFJ was biologically active. Jasmine showed yellow spots after rubbing with total RNA extracted from Agro-infiltrated N. benthamiana, indicating that JaVH was highly associated with yellow mosaic symptoms observed on jasmine. To investigate the occurrence and mutations of the virus, jasmine samples were collected from eight provinces of China and were tested for JaVH. The samples that were tested positive for JaVH were used to determine the complete genome sequences. They were comprised of 3867 or 3868 nucleotides and their genome organizations resembled that we previous reported for JaVH-FJ. Phylogenetic analyses and sequence comparisons suggest that the eight virus isolates were close isolates of JaVH-FJ and the isolate from Jilin Province was most closely related to JaVH-FJ with 99.2% nucleotide identity over the entire genome and 99.7% identity of coat protein. Further comparative analyses of JaVH-FJ and JaVH-JL revealed additional nucleotide differences in the 3′-untranslated region (3′ UTR). An infectious clone of JaVH-JL and chimeric mutants containing JaVH-FJ or JaVH-JL 3′ UTRs were then constructed for further study. The differential accumulation of JaVH with distinct 3′ UTR suggested that the 3′ UTR of JaVH plays a crucial role in viral RNA accumulation.

This study explored the role of T cell subsets and the expression of related microRNAs in patients with recurrent early pregnancy loss (EPL). Fifty patients with EPL loss between May 2018 and May 2021 were randomly selected as the EPL group, and 50 pregnant women with normal pregnancies or normal delivery outcomes were randomly selected as the control group. The expression levels of T cell subset-related markers and T cell subset-related miRNAs, in addition to the frequencies of T cell subsets, in peripheral blood of the two groups were analyzed. In terms of T cell-related markers, the results showed that the expression levels of the transcriptional regulator TBX-21 (T-bet) and interferon regulatory factor 4 (IRF4) were significantly upregulated in peripheral blood of the patients in the EPL group ( P < 0.05 ), whereas the expression levels of GATA binding protein 3 (GATA3) and glucocorticoid-induced tumor necrosis factor receptor (GITR) were significantly downregulated ( P < 0.05 ). In the EPL group, the expression of mir-106b, mir-93, and mir-25 was upregulated ( 1.51 ± 0.129 , 1.43 ± 0.132 , and 1.73 ± 0.156 , respectively) in regulatory T (Treg) cell-related T cell subsets, whereas the expression of miR-146a and miR-155 was downregulated ( P < 0.05 ). The frequencies of Treg and exhausted T cells in the EPL group were significantly lower than those in the control group ( P < 0.05 ). The cell frequencies of T helper 17 (Th17) cells and exhausted Treg cells in the EPL group were significantly higher than those in the control group ( P < 0.05 ). In conclusion, immune cells and associated miRNA profiles can be used as prognostic biomarkers for the treatment of human reproductive disorders, such as EPL.

Supplemental material, sj-docx-1-tam-10.1177_17588359231177016 for Concurrent chemotherapy using taxane plus cisplatin versus cisplatin alone in high-risk nasopharyngeal carcinoma patients with suboptimal response to induction chemotherapy by Ya-Ni Zhang, Yu-Pei Chen, Ji-Bin Li, Tai-Xiang Lu, Fei Han and Chun-Yan Chen in Therapeutic Advances in Medical Oncology

To investigate the effect of electroacupuncture (EA) on the expression of β-amyloid (Aβ) and autophagy-related proteins in hippocampal cells of Alzheimer's disease (AD) model mice, so as to explore its underlying mechanisms.Eighteen male APP/PS1 transgenic mice (6 months old) were randomly divided into model and EA groups, with 9 mice in each group. Nine male C57BL/6 wild-type mice of the same age were chosen as the normal group. Mice in the EA group were treated with acupuncture on "Baihui" (GV20) and EA (1 Hz/50 Hz, 1 mA) on bilateral "Yongquan" (KI1), once every other day, 20 min each time for a total of 21 times. After the interventions, the spatial learning and memory ability were observed by Morris water maze test. The autophagy-related pathological changes in hippocampus were observed by transmission electron microscopy. The expressions of microtublue associated protein 1 light chain 3 (LC3) and Aβ in hippocampus were observed by immunofluorescence and the expression levels of LC3 and p62 proteins were detected by Western blot.Compared with the normal group, the escape latency was prolonged (EA can reduce the expression levels of autophagy-related proteins LC3 and p62 in APP/PS1 transgenic mice, improve the hip-pocampal autophagy state, reduce intracellular Aβ aggregation, and thus improve the learning and memory ability.

Menaquinone-7 (MK-7), a highly valuable member of the vitamin K2 series, is an essential nutrient for humans. It plays an important role in the treatment of coagulation, osteoporosis, promotion of liver function recovery and prevention of cardiovascular diseases. In this study, in order to further improve the metabolic synthesis of MK-7 by the mutant strain, the effect of metabolic synthesis of MK-7 by mutant strain Bacillus subitilis 168 KO-SinR (BS168 KO-SinR) was analyzed by adding surfactants. The results showed that the addition of surfactants changed the permeability of the cell membrane of the mutant strain and the structural components of the biofilm, as indicated by scanning electron microscopy and flow cytometry. When 0.7% Tween-80 was added into the medium, the extracellular and intracellular synthesis of MK-7 reached 28.8 mg/L and 59.2 mg/L, respectively, increasing the total synthesis of MK-7 by 80.3%. qRT-PCR showed that the addition of surfactant significantly increased the expression level of MK-7 synthesis-related genes, and the results of electron microscope showed that the addition of surfactant changed the permeability of cell membrane. The research results of this paper provide a certain reference value for the industrial development of MK-7 prepared by fermentation.

To evaluate the midterm outcomes of penetrating keratoplasty (PK) following allogeneic cultivated limbal epithelial transplantation (CLET) for bilateral total limbal stem cell deficiency (LSCD)，ten patients (10 eyes) with bilateral LSCD were enrolled in this prospective noncomparative case series study. Each participant received a PK approximately 6 months after a CLET. Topical tacrolimus, topical and systemic steroids, and oral ciclosporin were given postoperatively. Best-corrected visual acuity (BCVA), intraocular pressure (IOP), ocular surface grading scores (OSS), corneal graft epithelial rehabilitation, persistent epithelial defect (PED), immunological rejection, and graft survival rate were assessed. The time interval between PK and allogeneic CLET was 6.90 ± 1.29 (6-10) months. BCVA developed from 2.46±0.32 LogMAR preoperatively to 0.77±0.55 LogMAR post-PK (P

AIM: To explore the expression of cGAS/STING signaling components in Mooren’s ulcer (MU). METHODS: Samples were obtained from ten MU patients, and eight residual corneal-scleral rings of healthy donor corneas for controls. Human corneal epithelial cells (HCECs) were used to evaluate the effect of cGAS/STING signaling pathway. Immunohistochemistry (IHC) and Western blot were used to examine the expression of cGAS, STING, and phosphorylated interferon regulatory factor 3 (p-IRF3) in MU tissues. The expression of interferon-β (IFN-β) and interferon-stimulated genes (ISGs) was quantified by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). RESULTS: The protein levels of cGAS and STING in MU samples were significantly elevated when compared with the healthy controls by Western blot and IHC. After stimulation with cGAMP, real-time PCR and ELISA showed a dramatic increase of IFN-β and ISGs (containing CXCL10, IFIT1, and IL-6) in HCECs. Moreover, HCECs treated with cGAMP was characterized by increased phosphorylation and more nuclear translocation of IRF3. Meanwhile, increased p-IRF3 was observed in MU samples via IHC and Western blot. CONCLUSION: The pronounced expression of cGAS/STING signaling components in the patients with MU and probably contribute to the onset and development of MU.

Accurate wind speed forecasting is very crucial for wind power generation systems, but the inherent randomness of wind speeds makes wind speed forecasting challenging. There have been many studies on predicting wind speeds, but they ignored the influence factor of wind speed on its change over time with multiple factors, such as wind direction, temperature, humidity and atmospheric pressure. Therefore, a secondary factor induced wind speed time series prediction using self-adaptive interval type-2 fuzzy sets (IT2FS) with error correction was proposed. First, an IT2FS model is developed to induce secondary factors to predict wind speed. Specifically, the differential evolution algorithm is employed to optimize parameters of IT2FS model. Second, error correction strategy is adopted to correct the model error. The auto-regressive integrated moving average model is used to predict the residual sub-sequence after variational mode decomposition. Finally, by predicting the wind speed of two wind farms in China, it is verified that the proposed hybrid system transcends other compared models and simultaneously realizes high accuracy and strong stability. Thus, employing a new strategy to conduct the main factor time series prediction using its secondary factors is extremely useful for enhancing the prediction performance.

Pseudomonas aeruginosa DN1 can efficiently utilize fluoranthene as its sole carbon source, and the initial reaction in the biodegradation process is catalyzed by a ring-hydroxylating dioxygenase (RHD). To clarify the binding interaction of RHD with fluoranthene in the strain DN1, the genes encoding alpha subunit (RS30940) and beta subunit (RS05115) of RHD were functionally characterized through multi-technique combination such as gene knockout and homology modeling as well as molecular docking analysis. The results showed that the mutants lacking the characteristic alpha subunit and/or beta subunit failed to degrade fluoranthene effectively. Based on the translated protein sequence and Ramachandran plot, 96.5% of the primary amino-acid sequences of the alpha subunit in the modeled structure of the RHD were in the permitted region, 2.3% in the allowed region, but 1.2% in the disallowed area. The catalytic mechanism mediated by key residues was proposed by the simulations of molecular docking, wherein the active site of alpha subunit constituted a triangle structure of the mononuclear iron atom and the two oxygen atoms coupled with the predicted catalytic ternary of His217-His222-Asp372 for the dihydroxylation reaction with fluoranthene. Those amino acid residues adjacent to fluoranthene were nonpolar groups, and the C7-C8 positions on the fluoranthene ring were estimated to be the best oxidation sites. The distance of C7-O and C8-O was 3.77 Å and 3.04 Å respectively, and both of them were parallel. The results of synchronous fluorescence and site-directed mutagenesis confirmed the roles of the predicted residues during catalysis. This binding interaction could enhance our understanding of the catalytic mechanism of RHDs and provide a solid foundation for further enzymatic modification.

The current global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of COVID-19 has infected hundreds of millions of people, killed millions, and continues to pose a threat. It has become one of the largest epidemics in human history, causing enormous damage to people’s lives and economies in the whole world. However, there are still many uncertainties and continued attention to the impact of SARS-CoV-2 on human health. The entry of SARS-CoV-2 into host cells is facilitated by the binding of the spike protein on the virus surface to the cell surface receptor angiotensin-converting enzyme 2 (ACE2). Furthermore, transmembrane protease serine 2 (TMPRSS2) is a host surface protease that cleaves and proteolytically activates its S protein, which is necessary for viral infection. Thus, SARS-CoV-2 uses the ACE2 receptor for cell entry and initiates the S protein using the protease TMPRSS2. Schizophyllum commune (SC) is one of the most widely distributed fungi, often found on the rotten wood of trees that has been found to have various health benefits, including anticancer, antimicrobial activity, antiparasitic, and immunomodulatory function. In this article, SC significantly diminished the expression ACE2 and TMPRSS2 protein in vitro and in vivo without cell damage. In addition, adenosine from SC was also proven in this experiment to reduce the ACE2 and TMPRSS2 expression. Thus, our findings suggest that SC and adenosine exhibit potential for the repression of SARS-CoV-2 infection via the ACE2 and TMPRSS2 axis.