Advances in generative modeling methods and datasets to design novel enzymes for renewable chemicals and fuels.

Biotechnology has revolutionized the development of sustainable energy sources by harnessing biomass as a feedstock for energy production. However, challenges such as recalcitrant feedstocks and inefficient metabolic pathways hinder the large-scale integration of renewable energy systems. Enzyme engineering has emerged as a powerful tool to address these challenges by enhancing enzyme activity, specificity, and stability. Generative machine learning (ML) models have shown great promise in accelerating protein design, allowing for the generation of novel protein sequences with desired properties by navigating vast spaces. This review paper aims to summarize the state of the art in generative models for protein design and how they can be applied to bioenergy applications, including the underlying architectures and training strategies. Additionally, it highlights the importance of high-quality datasets for training and evaluating generative models, organizes available datasets for generative protein design, and discusses the potential of applying generative models to strain design for bioenergy production.

Prevalence of osteoporosis in patients awaiting unicompartmental knee arthroplasty: a cross-sectional study.

Objectives: Osteoporosis may contribute to failure of unicompartmental knee arthroplasty (UKA), yet the prevalence of osteoporosis in the population awaiting UKA has not been adequately studied. The objectives of this study were to report the prevalence of osteoporosis in people awaiting UKA and the rate of anti-osteoporosis treatment, and to explore factors associated with osteoporosis prevalence in people awaiting UKA. Methods: Participants awaiting UKA from January 2019 to May 2023 were consecutively enrolled. Participants ' age, gender, BMI, knee K-L score, VAS score, history of previous DXA testing, history of anti-osteoporosis treatment, and possible underlying risk factors were recorded. All participants were given a dual-energy x-ray absorptiometry (DXA) test after the visit. The diagnosis of osteoporosis was made according to the World Health Organization criteria. Compare the prevalence of osteoporosis between people waiting for UKA and the general population. Risk factors associated with osteoporosis were analyzed using multiple linear regression and binary logistic regression models. Results: A total of 340 participants were included in the study, 259 in female and 81 in male, with a mean age of 63.53 years (range: 41-84 years), and all participants completed UKA and had DXA prior to UKA. The prevalence of osteoporosis was 40.88% (44.79% in female and 28.40% in male). The prevalence of osteoporosis was higher in female than in male (p<0.001). The prevalence of osteoporosis in the population waiting for UKA was significantly higher than that in the general population (p < 0.001). DXA testing was performed in 12.06% within 1 year prior to the visit. The percentage of those who had received anti-osteoporosis treatment was 20.59% (20.86% in osteoporosis, 22.39% in Osteopenia and 16.42% in normal bone mass). The correlation between age, gender, body mass index, visual analogue scale score and osteoporosis was statistically significant. Conclusion: Osteoporosis is common in people waiting for UKA, but screening and treatment rates are low. Female patients of advanced age and low weight combined with significant pain should be considered for osteoporosis screening and appropriate treatment before UKA.

Neuronal diversity of neuropeptide signaling, including galanin, in the mouse locus coeruleus.

The locus coeruleus (LC) is a small nucleus in the pons from which ascending and descending projections innervate major parts of the central nervous system. Its major transmitter is norepinephrine (NE). This system is evolutionarily conserved, including in humans, and its functions are associated with wakefulness and related to disorders, such as depression. Here, we performed single-cell ribonucleic acid-sequencing (RNA-seq) to subdivide neurons in the LC (24 clusters in total) into 3 NE, 17 glutamate, and 5 γ-aminobutyric acid (GABA) subtypes, and to chart their neuropeptide, cotransmitter, and receptor profiles. We found that NE neurons expressed at least 19 neuropeptide transcripts, notably galanin (Gal) but not Npy, and >30 neuropeptide receptors. Among the galanin receptors, Galr1 was expressed in ~19% of NE neurons, as was also confirmed by in situ hybridization. Unexpectedly, Galr1 was highly expressed in GABA neurons surrounding the NE ensemble. Patch-clamp electrophysiology and cell-type-specific Ca2+-imaging using GCaMP6s revealed that a GalR1 agonist inhibits up to ~35% of NE neurons. This effect is direct and does not rely on feed-forward GABA inhibition. Our results define a role for the galanin system in NE functions, and a conceptual framework for the action of many other peptides and their receptors.

[Comparison of outcomes of mixed unicompartmental knee arthroplasty and total knee arthroplasty in the treatment of medial osteoarthritis of the knee].

OBJECTIVE: To evaluate outcomes of mixed unicompartmental knee arthroplasty(UKA) and total knee arthroplasty(TKA) in the treatment of medial osteoarthritis(OA) of the knee. METHODS: Retrospective analysis of 156 patients, 44 males and 112 females, aged from 50 to 75 years old with an average of(58.76±4.97) years old, who underwent knee arthroplasty from October 2017 to October 2019. The patients were divided into two groups:81 cases(81 knees) underwent TKA, including 23 males and 58 females, aged from 51 to 75 years old with an average of (58.60±5.01) years old, and 75 case (75 knees) underwent UKA with mixed phase 3 Oxford, including 21 males and 54 females, aged from 50 to 72 years old with an average of (58.92±4.95) years old. The two groups were compared regarding to the clinical outcomes, assessed using surgical information and complications, American Knee Society score(AKSS) clinical score and functional score. Radiographs were assessed using hip-knee-ankle angle(HKA), tibial component valgus/varus angle(TCVA), tibial component posterior slope angle(TCPSA), femoral component valgus/varus angle(FCVA), femoral component posterior slope angle(FCPSA), looking for bearing dislocation, prosthesis loosening, progression of OA in lateral compartment. RESULTS: Intraoperative bleeding, operative time and hospital days were significantly better in the UKA group than in the TKA group (P<0.05), and there were no postoperative complications in either group. Patients in both groups were enrolled with an average follow-up time of (38.01±8.90) months, ranged from 24 to 54 months. AKSS functional, AKSS clinical, HKA in both groups significantly improved at the final follow-up compared with those before operation. At the final follow-up, the UKA group was significantly better than the TKA group in AKSS functional and AKSS clinical, whereas HKA in the TKA group was better. At the final follow-up. TCVA and FCVA between the two groups were not significantly different, while TCPSA and FCPSA in the UKA group were significantly greater than the TKA group. No signs of progression of OA to the lateral compartment were observed. CONCLUSION: Mixed phase 3 Oxford UKA in medial unicompartmental knee osteoarthritis was considerably better than TKA for less blood loss, shorter operation time, shorter hospital stay, rapid postoperative recovery, helping achieve satisfactory function, provided satisfactory outcome.

Topographic Cues of a PLGA Scaffold Promote Odontogenic Differentiation of Dental Pulp Stem Cells through the YAP/ß-Catenin Signaling Axis.

PURPOSE: The underlying mechanism of how topographic cues of artificial scaffolds regulate cell function remains poorly understood. Yes-associated protein (YAP) and ß-catenin signaling have both been reported to play important roles in mechano-transduction and dental pulp stem cells (DPSCs) differentiation. We investigated the effects of YAP and ß-catenin in spontaneous odontogenic differentiation of DPSCs induced by topographic cues of a poly(lactic-co-glycolic acid) (PLGA) membrane. METHODS: The topographic cues and function of a fabricated PLGA scaffold were explored via scanning electron microscopy (SEM), alizarin red staining (ARS), reverse transcription-polymerase chain reaction (RT-PCR), and pulp capping. Immunohistochemistry (IF), RT-PCR, and western blotting (WB) were used to observe the activation of YAP and ß-catenin when DPSCs were cultured on the scaffolds. Further, YAP was inhibited or overexpressed on either side of the PLGA membrane, and YAP, ß-catenin, and odontogenic marker expression were analyzed using IF, ARS, and WB. RESULTS: The closed side of the PLGA scaffold promoted spontaneous odontogenic differentiation and nuclear translocation of YAP and ß-catenin in vitro and in vivo compared to the open side. The YAP antagonist verteporfin inhibited ß-catenin expression, nuclear translocation, and odontogenic differentiation on the closed side, but the effects were rescued by LiCl. YAP overexpressing DPSCs on the open side activated ß-catenin signaling and promoted odontogenic differentiation. CONCLUSION: The topographic cue of our PLGA scaffold promotes odontogenic differentiation of DPSCs and pulp tissue through the YAP/ß-catenin signaling axis.

Phloretin decreases microglia-mediated synaptic engulfment to prevent chronic mild stress-induced depression-like behaviors in the mPFC.

Background: Stress is an important risk factor to induce psychiatric disorders such as depression. Phloretin (PHL), a natural dihydrochalcone compound, has been shown to exhibit anti-inflammatory and anti-oxidative effects. However, the impact of PHL on the depression and the underlying mechanism remain unclear. Methods: The animal behavior tests were used to determine the protective of PHL on the chronic mild stress (CMS)-induced depression-like behaviors. The Magnetic Resonance Imaging (MRI), electron microscopy analysis, fiber photometry, electrophysiology, and Structure Illumination Microscopy (SIM) were used to investigate the protective of PHL on the structural and functional impairments induced by CMS exposure in the mPFC. The RNA sequencing, western blot, reporter gene assay, and chromatin immunoprecipitation were adopted to investigate the mechanisms. Results: We showed that PHL efficiently prevented the CMS-induced depressive-like behaviors. Moreover, PHL not only attenuated the decrease of synapse losses but also improved the dendritic spine density and neuronal activity in the mPFC after CMS exposure. Furthermore, PHL remarkably inhibited the CMS-induced microglial activation and phagocytic activity in the mPFC. In addition, we demonstrated that PHL decreased the CMS-induced synapse losses by inhibiting the deposition of complement C3 deposition onto synapses and subsequent microglia-mediated synaptic engulfment. Finally, we revealed that PHL inhibited the NF-κB-C3 axis to display neuroprotective effects. Conclusions: Our results indicate that PHL represses the NF-κB-C3 axis and subsequent microglia-mediated synaptic engulfment to protect against CMS-induced depression in the mPFC.

A Randomized, Double-Blind, Placebo-Controlled, Phase 1 Trial of Radiopaque Islatravir-Eluting Subdermal Implants for Pre-exposure Prophylaxis Against HIV-1 Infection.

BACKGROUND: Islatravir (MK-8591) is a deoxyadenosine analog in development for the treatment and prevention of HIV-1 infection. An islatravir-eluting implant could provide an additional option for pre-exposure prophylaxis (PrEP). SETTING: Previous data support a threshold islatravir triphosphate concentration for PrEP of 0.05 pmol/10 6 cells in peripheral blood mononuclear cells. Prototype islatravir-eluting implants were previously studied to establish general tolerability and pharmacokinetics (PKs) of islatravir relative to the threshold level. METHODS: In this randomized, double-blind, placebo-controlled, phase 1 trial, a next-generation radiopaque islatravir-eluting implant (48 mg, 52 mg, or 56 mg) or placebo implant was placed for a duration of 12 weeks in participants at low risk of HIV infection. Safety and tolerability, as well as PK for islatravir parent and islatravir triphosphate from plasma and peripheral blood mononuclear cells, were assessed throughout placement and 8 weeks after removal. RESULTS: In total, 36 participants (8 active and 4 placebo per dose arm) were enrolled and completed this study. Implants were generally well tolerated, with no discontinuations due to an adverse event, and no clear dose-dependence in implant-related adverse events. No clinically meaningful relationships were observed for changes in laboratory values, vital signs, or electrocardiogram assessments. Mean islatravir triphosphate levels at day 85 (0.101-0.561 pmol/10 6  cells) were above the PK threshold for all dose levels. CONCLUSION: Islatravir administered using a subdermal implant has the potential to be an effective and well-tolerated method for administering PrEP to individuals at risk of acquiring HIV-1.

Serum amyloid P component (SAP) modulates antidepressant effects through promoting membrane insertion of the serotonin transporter.

Serum amyloid P component (SAP) is a universal constituent of human amyloid deposits including those in Alzheimer's disease. SAP has been observed to be elevated in patients with depression, and higher SAP levels are associated with better response to the antidepressant escitalopram. The mechanisms underlying these clinical observations remain unclear. We examined the effect of SAP on serotonin transporter (SERT) expression and localization using Western blot, confocal microscopy, and positron emission tomography with the radioligand [11C]DASB. We also investigated the effect of SAP on treatment response to escitalopram in mice with the forced swim test (FST), a classical behaviour paradigm to assess antidepressant effects. SAP reduced [11C]DASB binding as an index of SERT levels, consistent with Western blots showing decreased total SAP protein because of increased protein degradation. In conjunction with the global decrease in SERT levels, SAP also promotes VAMP-2 mediated SERT membrane insertion. SAP levels are correlated with behavioural despair and SSRI treatment response in mice with FST. In MDD patients, the SAP and membrane SERT levels are correlated with response to SSRI treatment. SAP has complex effects on SERT levels and localization, thereby modulating the effect of SSRIs, which could partially explain clinical variability in antidepressant treatment response. These results add to our understanding of the mechanism for antidepressant drug action, and with further work could be of clinical utility.

Enzyme Activity Prediction of Sequence Variants on Novel Substrates using Improved Substrate Encodings and Convolutional Pooling.

Protein engineering is currently being revolutionized by deep learning applications, especially through natural language processing (NLP) techniques. It has been shown that state-of-the-art self-supervised language models trained on entire protein databases capture hidden contextual and structural information in amino acid sequences and are capable of improving sequence-to-function predictions. Yet, recent studies have reported that current compound-protein modeling approaches perform poorly on learning interactions between enzymes and substrates of interest within one protein family. We attribute this to low-grade substrate encoding methods and over-compressed sequence representations received by downstream predictive models. In this study, we propose a new substrate-encoding based on Extended Connectivity Fingerprints (ECFPs) and a convolutional-pooling of the sequence embeddings. Through testing on an activity profiling dataset of haloalkanoate dehalogenase superfamily that measures activities of 218 phosphatases against 168 substrates, we show substantial improvements in predictive performances of compound-protein interaction modeling. In addition, we also test the workflow on three other datasets from the halogenase, kinase and aminotransferase families and show that our pipeline achieves good performance on these datasets as well. We further demonstrate the utility of this downstream model architecture by showing that it achieves good performance with six different protein embeddings, including ESM-1b (Rives et al., 2021), TAPE (Rao et al., 2019), ProtBert, ProtAlbert, ProtT5, and ProtXLNet (Elnaggar et al., 2021). This study provides a new workflow for activity prediction on novel substrates that can be used to engineer new enzymes for sustainability applications.

Examining the effects of self-regulated learning-based teacher feedback on English-as-a-foreign-language learners' self-regulated writing strategies and writing performance.

The current study examines the effect of teacher feedback on fostering self-regulated English-as-a-foreign-language (EFL) writers. Adopting a quasi-experimental design, this study was conducted among seventy students from two parallel intact English writing classes at the tertiary level. While conventional feedback at the level of task was used in the control group, feedback at the level of process and self-regulation with supplementary activities was adopted for the treatment group. This SRL-based feedback intervention lasted one semester. Students took a pre-test, an immediate and a delayed post-test to measure their improvement in English writing performance, as well as their use of writing strategies for self-regulated learning (SRL), with a questionnaire. The results reveal that the SRL-based feedback intervention had a positive impact on EFL student writers' writing performance as well as their reported use of SRL writing strategies. While the analytic writing scores for the subcategories of organisation, vocabulary and content significantly increased over time for the treatment group, there was little change in language use. ANCOVA analyses suggest significantly positive results for the treatment group in the improvement of SRL writing strategies with goal-oriented monitoring, knowledge rehearsal, feedback handling, and interest enhancement, and the intervention also developed the use of SRL strategies for text processing, idea planning, motivational self-talk, and emotional control.

Cocaine increases quantal norepinephrine secretion through NET-dependent PKC activation in locus coeruleus neurons.

The norepinephrine neurons in locus coeruleus (LC-NE neurons) are essential for sleep arousal, pain sensation, and cocaine addiction. According to previous studies, cocaine increases NE overflow (the profile of extracellular NE level in response to stimulation) by blocking the NE reuptake. NE overflow is determined by NE release via exocytosis and reuptake through NE transporter (NET). However, whether cocaine directly affects vesicular NE release has not been directly tested. By recording quantal NE release from LC-NE neurons, we report that cocaine directly increases the frequency of quantal NE release through regulation of NET and downstream protein kinase C (PKC) signaling, and this facilitation of NE release modulates the activity of LC-NE neurons and cocaine-induced stimulant behavior. Thus, these findings expand the repertoire of mechanisms underlying the effects of cocaine on NE (pro-release and anti-reuptake), demonstrate NET as a release enhancer in LC-NE neurons, and provide potential sites for treatment of cocaine addiction.

Advances in Immunosuppressive Agents Based on Signal Pathway.

Immune abnormality involves in various diseases, such as infection, allergic diseases, autoimmune diseases, as well as transplantation. Several signal pathways have been demonstrated to play a central role in the immune response, including JAK/STAT, NF-κB, PI3K/AKT-mTOR, MAPK, and Keap1/Nrf2/ARE pathway, in which multiple targets have been used to develop immunosuppressive agents. In recent years, varieties of immunosuppressive agents have been approved for clinical use, such as the JAK inhibitor tofacitinib and the mTOR inhibitor everolimus, which have shown good therapeutic effects. Additionally, many immunosuppressive agents are still in clinical trials or preclinical studies. In this review, we classified the immunosuppressive agents according to the immunopharmacological mechanisms, and summarized the phase of immunosuppressive agents.

Update on GPCR-based targets for the development of novel antidepressants.

Traditional antidepressants largely interfere with monoaminergic transport or degradation systems, taking several weeks to have their therapeutic actions. Moreover, a large proportion of depressed patients are resistant to these therapies. Several atypical antidepressants have been developed which interact with G protein coupled receptors (GPCRs) instead, as direct targeting of receptors may achieve more efficacious and faster antidepressant actions. The focus of this review is to provide an update on how distinct GPCRs mediate antidepressant actions and discuss recent insights into how GPCRs regulate the pathophysiology of Major Depressive Disorder (MDD). We also discuss the therapeutic potential of novel GPCR targets, which are appealing due to their ligand selectivity, expression pattern, or pharmacological profiles. Finally, we highlight recent advances in understanding GPCR pharmacology and structure, and how they may provide new avenues for drug development.

Effect of the cPKCγ-Ng Signaling System on Rapid Eye Movement Sleep Deprivation-Induced Learning and Memory Impairment in Rats.

Objective: Rapid eye movement sleep deprivation (REM-SD) can cause a decline in learning and memory and lead to changes in behavior. Therefore, REM sleep plays a key role in processes that govern learning and memory. However, the mechanism underlying REM-SD-induced learning and memory impairment is unclear and the underlying molecular signaling still needs to be identified. In the present study, we investigated the role of the cPKCγ-Ng signaling pathway in REM-SD-induced learning and memory impairment. Method: Sixty male rats were divided into Control, REM-SD, REM-SD+cPKCγ activator PMA, REM-SD+cPKCγ inhibitor H-7, and sleep revival (SR) groups. The Morris water maze was used to assess spatial learning and memory. Western blot analysis was used to detect cPKCγ total protein expression and membrane translocation levels, and Ng total protein expression and phosphorylation levels. Results: The REM-SD group performed worse on the Morris water maze test than the control group. Western blot analysis showed that cPKCγ membrane translocation and Ng phosphorylation levels were significantly lower in the REM-SD group. SR following REM-SD restored learning and memory ability, cPKCγ transmembrane translocation, and Ng phosphorylation levels, but not to levels observed before REM-SD. PMA and H-7 significantly improved/disrupted task ability as well as cPKCγ transmembrane translocation and Ng phosphorylation levels in REM-SD rats. Conclusion: The REM-SD induced learning and memory impairment in rats and may be associated with the cPKCγ-Ng signaling pathway. Specifically, activation of the cPKCγ-Ng signaling pathway may protect against REM-SD.

A duplex SYBR green I-based real-time polymerase chain reaction assay for concurrent detection of feline parvovirus and feline coronavirus.

Feline coronavirus (FCoV) contains two serotypes, feline enteric coronavirus (FECV) and Feline infectious peritonitis virus (FIPV). FECV and feline parvovirus (FPV) can cause similar clinical symptoms in cats, such as diarrhea. The objective of this study was to establish a duplex SYBR Green I-based quantitative polymerase chain reaction (qPCR) assay for rapid and simultaneous detection of FPV and FCoV. Two pairs of specific PCR primers were designed to target fragments of the VP2 gene of FPV and of the 5' UTR gene of FCoV, respectively. The assay distinguished between the two viruses based on the melting curves (melting temperatures 77.0 ± 0.5 °C [FPV] and 80.5 ± 0.5 °C [FCoV]). The minimum limits of FPV and FCoV detection were 4.74 × 101 copies/µL and 7.77 × 101 copies/µL, respectively. The assay showed excellent reproducibility and reliability, based on the mean coefficient of variation. In conclusion, this novel duplex SYBR Green I-based qPCR assay is sensitive and can specifically, reliably, and rapidly detect FPV and FCoV (co-)infections.

[Main components in butyl alcohol extract of Baitouweng Decoction inhibited neutrophil chemotaxis].

The present study aims to investigate the effects of the main components(aesculin, berberine hydrochloride, and anemoside B4) in the butyl alcohol extract of Baitouweng Decoction(BAEB) on the chemotaxis of neutrophils induced by dimethyl sulfoxide(DMSO). HL60 cells were cultivated in RPMI-1640 complete medium, and transferred into a 6-well plate(2 × 10~5 per mL) with 4 mL in each well, followed by incubation with DMSO at 1.3% for five days. The morphologic changes of cells were observed under an inverted microscope. The CD11 b expression after DMSO induction was analyzed by flow cytometry. The effects of aesculin, berberine hydrochloride, and anemoside B4 on the cell proliferation and migration were detected by CCK8 assay and Transwell assay, respectively. The effects of the main components on the production and polarization of F-actin protein were also examined by flow cytometry and laser confocal microscopy. PI3 K/Akt signaling pathway was checked by Western blot. As revealed by the results, neutrophil-like HL60 cells were observed after DMSO induction. The CD11 b expression in these cells increased significantly as indicated by the flow cytometry. Additionally, 100 µg·mL~(-1) aesculin, 8 µg·mL~(-1) berberine hydrochloride, and 80 µg·mL~(-1) anemoside B4 were potent in inhibiting the migration of neutrophils and reducing F-actin expression. Berberine hydrochloride was verified to be capable of diminishing phosphorylated PI3 K/Akt protein expression. The findings indicate that aesculin, anemoside B4, and especially berberine hydrochloride in the BAEB can inhibit the chemotaxis of neutrophils, which is possibly achieved by the inhibition of F-actin and PI3 K/Akt signaling pathway.

Involvement of Scratch2 in GalR1-mediated depression-like behaviors in the rat ventral periaqueductal gray.

Galanin receptor1 (GalR1) transcript levels are elevated in the rat ventral periaqueductal gray (vPAG) after chronic mild stress (CMS) and are related to depression-like behavior. To explore the mechanisms underlying the elevated GalR1 expression, we carried out molecular biological experiments in vitro and in animal behavioral experiments in vivo. It was found that a restricted upstream region of the GalR1 gene, from -250 to -220, harbors an E-box and plays a negative role in the GalR1 promoter activity. The transcription factor Scratch2 bound to the E-box to down-regulate GalR1 promoter activity and lower expression levels of the GalR1 gene. The expression of Scratch2 was significantly decreased in the vPAG of CMS rats. Importantly, local knockdown of Scratch2 in the vPAG caused elevated expression of GalR1 in the same region, as well as depression-like behaviors. RNAscope analysis revealed that GalR1 mRNA is expressed together with Scratch2 in both GABA and glutamate neurons. Taking these data together, our study further supports the involvement of GalR1 in mood control and suggests a role for Scratch2 as a regulator of depression-like behavior by repressing the GalR1 gene in the vPAG.

[Effect of berberine hydrochloride on cell wall integrity of Candida albicans hypha].

The aim of this paper was to investigate the effect of berberine hydrochloride on the cell wall integrity of Candida albicans hypha. The minimal inhibitory concentration(MIC) of berberine hydrochloride against clinical and standard C. albicans strains was detected by micro liquid-based dilution method; the effect of berberine hydrochloride on the colony formation of C. albicans SC5314 was investigated by spot assay; the effect of berberine hydrochloride on the metabolism of C. albicans SC5314 hypha was checked by XTT reduction assay, and the viability of C. albicans SC5314 hypha was tested by fluorescent staining assay. The effect of berberine hydrochloride on the morphology of C. albicans SC5314 hypha was examined by scanning electron microscope. The changes in the cell wall of C. albicans SC5314 hypha after berberine hydrochloride treatment were detected by transmission electron microscopy. The effect of berberine hydrochloride on ß-glucan from C. albicans SC5314 was detected by flow cytometry. The effect of berberine hydrochloride on hypha-specific gene ECE1 and ß-glucan synthase genes FKS1 and FKS2 in C. albicans was examined by qRT-PCR. The results showed that berberine hydrochloride showed a strong inhibitory effect on both clinical and standard strains of C. albicans, and the MIC was 64-128 µg·mL~(-1). Spot assay, XTT redunction assay and fluorescent staining assay showed that with the increase of berberine hydrochloride concentration, the viability of C. albicans SC5314 gradually decreased. The transmission electron microscopy scanning assay showed that this compound could cause cell wall damage of C. albicans. The flow cytometry analysis showed the exposure degree of C. albicans ß-glucan. The qRT-PCR further showed that berberine hydrochloride could significantly down-regulate hypha-specific gene ECE1 and ß-glucan synthase-related gene FKS1 and FKS2. In conclusion, this compound can down-regulate C. albicans and ß-glucan synthase-related gene expressions, so as to destroy the cell wall structure of C. albicans, expose ß-glucan and damage the integrity of the wall.

Corrigendum: Effect of the cPKCγ-Ng Signaling System on Rapid Eye Movement Sleep Deprivation-Induced Learning and Memory Impairment in Rats.

[This corrects the article DOI: 10.3389/fpsyt.2021.763032.].