Clinical practice guidelines for prevention and treatment of postoperative gastrointestinal disorder with Integrated Traditional Chinese and Western Medicine (2023).

Postoperative gastrointestinal disorder (POGD) was a common complication after surgery under anesthesia. Strategies in combination with Traditional Chinese Medicine and Western medicine showed some distinct effects but standardized clinical practice guidelines were not available. Thus, a multidisciplinary expert team from various professional bodies including the Perioperative and Anesthesia Professional Committees of the Chinese Association of Integrative Medicine (CAIM), jointly with Gansu Province Clinical Research Center of Integrative Anesthesiology/Anesthesia and Pain Medical Center of Gansu Provincial Hospital of Traditional Chinese Medicine and WHO Collaborating Center for Guideline Implementation and Knowledge Translation/Chinese Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Center/Gansu Provincial Center for Medical Guideline Industry Technology/Evidence-based Medicine Center of Lanzhou University, was established to develop evidence-based guidelines. Clinical questions (7 background and 12 clinical questions) were identified through literature reviews and expert consensus meetings. Based on systematic reviews/meta-analyses, evidence quality was analyzed and the advantages and disadvantages of interventional measures were weighed with input from patients' preferences. Finally, 20 recommendations were developed through the Delphi-based consensus meetings. These recommendations included disease definitions, etiologies, pathogenesis, syndrome differentiation, diagnosis, and perioperative prevention and treatment.

Structure-Based Discovery of the SARS-CoV-2 Main Protease Noncovalent Inhibitors from Traditional Chinese Medicine.

Traditional Chinese medicine (TCM) has been extensively employed for the treatment of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there is demand for discovering more SARS-CoV-2 Mpro inhibitors with diverse scaffolds to optimize anti-SARS-CoV-2 lead compounds. In this study, comprehensive in silico and in vitro assays were utilized to determine the potential inhibitors from TCM compounds against SARS-CoV-2 Mpro, which is an important therapeutic target for SARS-CoV-2. The ensemble docking analysis of 18263 TCM compounds against 15 SARS-CoV-2 Mpro conformations identified 19 TCM compounds as promising candidates. Further in vitro testing validated three compounds as inhibitors of SARS-CoV-2 Mpro and showed IC50 values of 4.64 ± 0.11, 7.56 ± 0.78, and 11.16 ± 0.26 µM, with EC50 values of 12.25 ± 1.68, 15.58 ± 0.77, and 29.32 ± 1.25 µM, respectively. Molecular dynamics (MD) simulations indicated that the three complexes remained stable over the last 100 ns of production run. An analysis of the binding mode revealed that the active compounds occupy different subsites (S1, S2, S3, and S4) of the active site of SARS-CoV-2 Mpro via specific poses through noncovalent interactions with key amino acids (e.g., HIS 41, ASN 142, GLY 143, MET 165, GLU 166, or GLN 189). Overall, this study provides evidence indicating that the three natural products obtained from TCM could be further used for anti-COVID-19 research, justifying the investigation of Chinese herbal medicinal ingredients as bioactive constituents for therapeutic targets.

Use of traditional Chinese medicine for the treatment and prevention of COVID-19 and rehabilitation of COVID-19 patients: An evidence mapping study.

Background: The potential effectiveness of traditional Chinese medicine (TCM) against "epidemic diseases" has highlighted the knowledge gaps associated with TCM in COVID-19 management. This study aimed to map the matrix for rigorously assessing, organizing, and presenting evidence relevant to TCM in COVID-19 management. Methods: In this study, we used the methodology of evidence mapping (EM). Nine electronic databases, the WHO International Clinical Trials Registry Platform (ICTRP) Search Portal, ClinicalTrials.gov, gray literature, reference lists of articles, and relevant Chinese conference proceedings, were searched for articles published until 23 March 2022. The EndNote X9, Rayyan, EPPI, and R software were used for data entry and management. Results: In all, 126 studies, including 76 randomized controlled trials (RCTs) and 50 systematic reviews (SRs), met our inclusion criteria. Of these, only nine studies (7.14%) were designated as high quality: four RCTs were assessed as "low risk of bias" and five SRs as "high quality." Based on the research objectives of these studies, the included studies were classified into treatment (53 RCTs and 50 SRs, 81.75%), rehabilitation (20 RCTs, 15.87%), and prevention (3 RCTs, 2.38%) groups. A total of 76 RCTs included 59 intervention categories and 57 efficacy outcomes. All relevant trials consistently demonstrated that TCM significantly improved 22 outcomes (i.e., consistent positive outcomes) without significantly affecting four (i.e., consistent negative outcomes). Further, 50 SRs included nine intervention categories and 27 efficacy outcomes, two of which reported consistent positive outcomes and two reported consistent negative outcomes. Moreover, 45 RCTs and 38 SRs investigated adverse events; 39 RCTs and 30 SRs showed no serious adverse events or significant differences between groups. Conclusion: This study provides evidence matrix mapping of TCM against COVID-19, demonstrating the potential efficacy and safety of TCM in the treatment and prevention of COVID-19 and rehabilitation of COVID-19 patients, and also addresses evidence gaps. Given the limited number and poor quality of available studies and potential concerns regarding the applicability of the current clinical evaluation standards to TCM, the effect of specific interventions on individual outcomes needs further evaluation.

pH-Sensitive and Biodegradable Mn3(PO4)2·3H2O Nanoparticles as an Adjuvant of Protein-Based Bivalent COVID-19 Vaccine to Induce Potent and Broad-Spectrum Immunity.

Developing a novel and potent adjuvant with great biocompatibility for immune response augmentation is of great significance to enhance vaccine efficacy. In this work, we prepared a long-term stable, pH-sensitive, and biodegradable Mn3(PO4)2·3H2O nanoparticle (nano-MnP) by simply mixing MnCl2/NaH2PO4/Na2HPO4 solution for the first time and employed it as an immune stimulant in the bivalent COVID-19 protein vaccine comprised of wild-type S1 (S1-WT) and Omicron S1 (S1-Omicron) proteins as antigens to elicit a broad-spectrum immunity. The biological experiments indicated that the nano-MnP could effectively activate antigen-presenting cells through the cGAS-STING pathway. Compared with the conventional Alum-adjuvanted group, the nano-MnP-adjuvanted bivalent vaccine elicited approximately 7- and 8-fold increases in IgG antibody titers and antigen-specific IFN-γ secreting T cells, respectively. Importantly, antisera of the nano-MnP-adjuvanted group could effectively cross-neutralize the SARS-CoV-2 and its five variants of concern (VOCs) including Alpha, Beta, Gamma, Delta, and Omicron, demonstrating that this bivalent vaccine based on S1-WT and S1-Omicron proteins is an effective vaccine design strategy to induce broad-spectrum immune responses. Collectively, this nano-MnP material may provide a novel and efficient adjuvant platform for various prophylactic and therapeutic vaccines and provide insights for the development of the next-generation manganese adjuvant.

Fermented Angelica sinensis activates Nrf2 signaling and modulates the gut microbiota composition and metabolism to attenuate D-gal induced liver aging.

Aging is an inevitable physiological process associated with an imbalance in the oxidative defense system. Angelica sinensis, a kind of traditional Chinese medicine (TCM), has anti-oxidant effects and has been considered as a potential supplement in anti-aging treatment. Nevertheless, it has the disadvantages of slow efficacy and long duration of treatment. Fermentation, as an efficient biotechnological approach, is beneficial for improving the nutritional capacity of the material. Fermented TCMs are considered to be more effective. In this study, fermented Angelica sinensis (FAS) and non-fermented Angelica sinensis (NFAS) were used to investigate changes in the chemical constituents. Furthermore, the improvement effect of FAS on D-galactose-induced aging in mice and the potential mechanisms were explored. The results revealed that FAS and NFAS had different constituents under the influence of fermentation, such as 3-phenyllactic acid, L-5-hydroxytryptophan, taxifolin and methyl gallate. These elevated constituents of FAS might help increase the ability of FAS to improve aging. The aging model was established by intraperitoneal injection of D-galactose (2.5 g kg-1 day-1) for 44 days, and FAS (3 g kg-1 day-1) was administered daily by oral gavage after 2 weeks of induction with D-galactose. FAS was observed to significantly ameliorate changes associated with liver aging, such as reduction of MDA, AGEs and 8-OHdG. The contents of pro-inflammatory cytokines containing TNF-α, IL-1ß and IL-6 were significantly suppressed in the FAS group. In addition, FAS activated Nrf2 signaling better than NFAS, improved the expression of Nrf2, HO-1, NQO1, GCLC, GCLM and GSS, and further increased the activities of SOD, CAT and other antioxidant enzymes in the liver. Simultaneously, it had a certain repair effect on the liver tissues of mice. The intestinal microbiota analysis showed that FAS could regulate the microbiota imbalance caused by aging, increase the ratio of Firmicutes/Bacteroidetes by 95% and improve the relative abundance of beneficial bacteria related to Nrf2 signaling, such as Lactobacillus. Besides, fecal metabolite analysis identified uric acid as an evidential metabolite, suggesting that FAS participates in purine metabolism to improve aging. Therefore, the regulation of intestinal microbiota and metabolism may be one of the important mechanisms of FAS in alleviating hepatic oxidative stress via the gut-liver axis. The results of this study could provide information for the future development of postbiotic products that may have beneficial effects on the prevention or treatment of aging.

Environmentally relevant concentrations of selenite trigger reproductive toxicity by affecting oocyte development and promoting larval apoptosis.

As a trace element, selenium (Se) has been widely added to food to maintain the physiological homeostasis of the organism. The adverse effects of Se on the reproduction of zebrafish have been investigated, however, the effects of Se on the maturation and apoptosis of zebrafish oocytes remain unclear. In this study, zebrafish embryos (2 h post fertilization, hpf) were exposed to 0, 12.5, 25, 50, and 100 µg Se/L for 120 days. The results demonstrated that exposure to selenite decreased the gonad-somatic index (GSI) and cumulative production of eggs, inhibited oocyte maturation (OM), and increased oocyte apoptosis in females. Exposure to selenite decreased the contents of sex hormones (E2) in the serum and increased the levels of reactive oxygen species (ROS) and cyclic adenosine monophosphate (cAMP) in the ovary. Furthermore, exposure to selenite downregulated the transcription level of genes on the HPG axis, decreased the phosphorylation level of CyclinB and the protein content of cAMP-dependent protein kinase (Pka), and upregulated the expression of genes (eif2s1a and chop) and proteins (Grp78, Chop) related to endoplasmic reticulum stress (ERS) and apoptosis. Moreover, maternal exposure to selenite resulted in the apoptosis of offspring and upregulated the content of ROS and the transcription level of genes related to ERS and apoptosis.

Fermented Astragalus and its metabolites regulate inflammatory status and gut microbiota to repair intestinal barrier damage in dextran sulfate sodium-induced ulcerative colitis.

Fermentation represents an efficient biotechnological approach to increase the nutritional and functional potential of traditional Chinese medicine. In this study, Lactobacillus plantarum was used to ferment traditional Chinese medicine Astragalus, the differential metabolites in the fermented Astragalus (FA) were identified by ultra-performance liquid chromatography-Q Exactive hybrid quadrupole-Orbitrap mass spectrometry (UPLC-Q-Exactive-MS), and the ameliorating effect of FA on dextran sulfate sodium (DSS)-induced colitis in mice were further explored. The results showed that 11 differential metabolites such as raffinose, progesterone and uridine were identified in FA, which may help improve the ability of FA to alleviate colitis. Prophylactic FA supplementation effectively improved DAI score, colon length and histopathological lesion in DSS-treated mice. The abnormal activation of the intestinal immune barrier in mice was controlled after FA supplementation, the contents of myeloperoxidase (MPO) and IgE were reduced and the contents of IgA were increased. The intestinal pro-inflammatory factors TNF-α, IL-1ß, IL-6, and IL-17 were down-regulated and the anti-inflammatory factors IL-10 and TGF-ß were up-regulated, suggesting that FA can intervene in inflammatory status by regulating the balance of Th1/Th2/Th17/Treg related cytokines. In addition, FA supplementation modified the structure of the intestinal microbiota and enriched the abundance of Akkermansia and Alistipes, which were positively associated with the production of short-chain fatty acids. These microbes and their metabolites induced by FA also be involved in maintaining the intestinal mucosal barrier integrity by affecting mucosal immunity. We observed that intestinal tight junction protein and mucous secreting protein ZO-1, occludin, and MUC2 genes expression were more pronounced in mice supplemented with FA compared to unfermented Astragalus, along with modulation of intestinal epithelial cells (IECs) apoptosis, verifying the intestinal mucosal barrier repaired by FA. This study is the first to suggest that FA as a potential modulator can more effectively regulate the inflammatory status and gut microbiota to repair the intestinal barrier damage caused by colitis.

Evidence and Mechanisms of Selenate Reduction to Extracellular Elemental Selenium Nanoparticles on the Biocathode.

Intracellular selenium nanoparticles (SeNPs) production is a roadblock to the recovery of selenium from biological water treatment processes because it is energy intensive to break microbial cells and then separate SeNPs. This study provided evidence of significantly more extracellular SeNP production on the biocathode (97-99%) compared to the conventional reactors (1-90%) using transmission electron microscopy coupled with energy-dispersive X-ray spectroscopy. The cathodic microbial community analysis showed that relative abundance of Azospira oryzae, Desulfovibrio, Stenotrophomonas, and Rhodocyclaceae was <1% in the inoculum but enriched to 10-21% for each group when the bioelectrochemical reactor reached a steady state. These four groups of microorganisms simultaneously produce intracellular and extracellular SeNPs in conventional biofilm reactors per literature review but prefer to produce extracellular SeNPs on the cathode. This observation may be explained by the cellular energetics: by producing extracellular SeNPs on the biocathode, microbes do not need to transfer selenate and the electrons from the cathode into the cells, thereby saving energy. Extracellular SeNP production on the biocathode is feasible since we found high concentrations of C-type cytochrome, which is well known for its ability to transfer electrons from electrodes to microbial cells and reduce selenate to SeNPs on the cell membrane.

The replacement of bacitracin methylene disalicylate with Bacillus subtilis PB6 in the diet of male Cherry Valley Ducks reduces the feed conversion ratio by improving intestinal health and modulating gut microbiota.

In this study, we compared the impacts of Bacillus subtilis PB6 (BS) and bacitracin methylene disalicylate (BMD) on the growth performance, intestinal morphology, expression of tight connection protein, and cecal microbiota community of male ducks through a 42-d trial. Three-hundred and sixty male Cherry Valley meat-type ducklings (1-day-old) were distributed into 3 groups of 6 replicates: CON group (control, basal diet), BMD group (basal diet + 45 mg/kg BMD, active ingredient dose in the feed), and BS group (basal diet + 2 × 107 CFU/kg BS in the feed). Results showed that supplementing the diet with BS reduced the average daily feed intake (ADFI) during d 15 to 42 and d 1 to 42 compared with the CON group (P = 0.032). It also reduced feed conversion ratio (FCR) during d 15 to 42 and d 1 to 42 (P < 0.05) relative to the other groups. The ileal villus height (VH) and villus height /crypt depth ratio (V/C) were increased (P < 0.05) in both the BS and BMD groups, and the jejunal VH and V/C ratio were increased in the BS group (P < 0.05). Relative to the CON, BS supplementation was associated with numerical augmentation of goblet cells in the jejunal mucosa and upregulation of jejunal zonula occludens (ZO-1) and ileal mucin2 (P < 0.05) mRNA levels. Analysis showed a negative correlation between FCR (d 0-42) and VH, V/C, and the number of goblet cells in the jejunum (P < 0.05). Additionally, BMD or BS supplementation altered the alpha diversity of colonic microbiota (P < 0.05). Correlation analysis revealed that Butyricimonas, Enterobacteriaceae, Clostridiaceae, and Tannerellaceae were positively associated with the acetic acid and butyrate concentrations (P < 0.05). Taken together, the supplementation of BS in the diet of male ducks was conducive to reducing FCR by meliorating intestinal morphology, upregulating ZO-1 and mucin2 mRNA levels, regulating the abundance of microbiota, and metabolites, and having a greater effect than BMD supplementation.

Mechanistic Investigation of Curcuma Protection against Oral Submucous Fibrosis.

Objective: Oral submucous fibrosis (OSMF) is a chronic, fibrotic disease that affects the oral cavity, showing a high rate of malignant transformation. Curcuma exerts therapeutic potentials in many diseases including OSMF. However, the potential targets and pathways to explain the therapeutic effects of curcuma on OSMF are outside the scope of present knowledge. Herein we intend to reveal the predictive targets and potential pathways of curcuma against OSMF by a network pharmacology-based approach followed by molecular docking technology. Methods: We searched the SymMap, GeneCards, and OMIM database to obtain curcuma and OSMF common targets. The protein-protein interaction (PPI) of curcuma and OSMF common targets were then analyzed, followed by functional enrichment analysis. The best binding mode of curcuma and target proteins was analyzed by molecular docking technology. Results: We collected 290 putative targets of curcuma molecules and 600 known therapeutic targets of OSMF, with 64 curcuma and OSMF common targets sorted out. In the PPI network, there were 63 nodes with 922 edges. The node indicates protein and the line indicates PPI relation. The most enriched GO term in the BP level is "gland development", followed by "cellular response to chemical stress", and then "response to oxygen levels", while the most enriched GO term in CC and MF is "membrane raft" and "cytokine receptor binding", respectively. We also found 131 KEGG pathways significantly enriched by curcuma and OSMF common targets. The binding energy of curcuma to ALB, TNF, TP53, IL6, and VEGFA was -9.5 kcal/mol, -3.9 kcal/mol, -3.5 kcal/mol, -3.6 kcal/mol, and -8.9 kcal/mol, respectively, which suggested ALB and VEGFA were regarded as main targets involving in the potential mechanism of curcuma against OSMF. Conclusion: The present study illustrated that the therapeutic effects of curcuma on OSMF were achieved by targeting ALB and VEGFA, which giving reference to further drug design and development for OSMF.

Exploring the effects of Chinese herbal ingredients on the signaling pathway of alopecia and the screening of effective Chinese herbal compounds.

ETHNOPHARMACOLOGICAL RELEVANCE: alopecia is a hair disorder that can add a significant medical and psychological burden to patients. Currently, the FDA-approved drugs for the treatment of androgenetic alopecia (AGA) are minoxidil and finasteride and immunosuppressives are therapeutic options for alopecia areata (AA), but the objective adverse effects and high cost of these treatments reduce patient compliance and thus the effectiveness of the drugs. Traditional Chinese medicine (TCM) has good efficacy, a high safety profile and low treatment costs, but its mechanism of action is still not fully understood. The use of signaling pathways to modulate hair loss is a major direction in the study of the pathogenesis and pharmacology of alopecia. AIM OF THE STUDY: This review aims to collect the results of experimental studies related to alopecia, to screen previously documented combinations of herbs claimed to be effective based on the herbs and their constituent compounds used in the identified studies, and to uncover other useful information that we hope will better guide the clinical application and scientific research of drug combinations or individual herbs for the treatment of alopecia. MATERIALS AND METHODS: We have reviewed experimental studies to determine the methods used and the mechanisms of action of the herbs and constituent compounds. The following keywords were searched in databases, including PubMed, EMBASE, CNKI and CSTJ." Medicinal plants" "Chinese herbal medicine", "hair loss", " alopecia", "androgenetic alopecia" and " alopecia areata ". We also collected combinations of drugs from books approved by various schools for screening. RESULTS: Using known combinations of compounds within herbal medicine to match the documented combinations, 34 topical combinations and 74 oral combinations were identified, and among the 108 herbal combinations screened Angelica, Rehmannia glutinosaLigusticum chuanxiong hort, Radix Rehmanniae, etc. The number of occurrences was very high, and the association with vascular drugs was also found to be very close. CONCLUSIONS: This review further elucidates the therapeutic mechanisms of the compounds within the herbal components associated with alopecia and screens for other combinations that may be dominated by this component for the treatment of alopecia, uncovering compounds from other drugs that may be key factors in the treatment of alopecia. This improvement will provide a better quality of evidence for the effectiveness of herbs and compounds used to treat alopecia.

LTM-TCM: A comprehensive database for the linking of Traditional Chinese Medicine with modern medicine at molecular and phenotypic levels.

Benefiting from the development of network pharmacology, Traditional Chinese Medicine (TCM) shows great potential in modern drug discovery. Recently, more and more TCM-related databases have been established for both academic and industry research, but they are still insufficient in data standardization, integrity, and precision. To better accelerate the TCM research and overcome these shortcomings, we construct a web-based TCM platform, LTM-TCM, which is currently the most comprehensive TCM database that includes the following advantages: (1) High-quality data integration from fourteen TCM authoritative databases, especially with additional manual collected 41,025 clinical treatment records and 213 ancient Chinese medical books. (2) Accurate correction of multi-source TCM interactions (between symptoms, prescriptions, herbs, ingredients and targets) through in-house Biomedical Natural Language Processing (BioNLP) approaches in more than 30 million articles. (3) Diverse cross-field pipelines (e.g., bioactive ingredients screening, targets prediction, and mechanism prediction, etc.) help integrating traditional medicine with modern science in common aspects at both the molecular and phenotypic levels. In summary, LTM-TCM contains 1928 symptoms, 48,126 prescriptions, 9122 plants, 34,967 ingredients, 13,109 targets and 1170,133 interactions among all TCM related components. LTM-TCM has both Chinese and English interfaces, and it is accessible at http://cloud.tasly.com/#/tcm/home.

Efficacy of hyperbaric oxygen therapy for diabetic foot ulcers: An updated systematic review and meta-analysis.

The present systematic review and meta-analysis was performed to evaluate the efficacy of hyperbaric oxygen therapy (HBOT) in the treatment of diabetic foot ulcers (DFUs). Relevant articles were retrieved from PubMed, the Cochrane Library, EMBASE and other databases through November 2020. A total of 20 randomized clinical trials and 1263 trials were included in the meta-analysis. For each trial, the average difference, odds ratio and 95% confidence interval were calculated to evaluate the efficacy. Hyperbaric oxygen therapy increased the healing rate of diabetic foot ulcers (relative risk, 1.901; 95% CI = 1.484-2.435, p < 0.0001), shortened the healing time (MD = -19.360; 95% CI = -28.753~-9.966, p < 0.001), and reduced the incidence of major amputation (relative risk, 0.518, 95% CI = 0.323-0.830, P < 0.01). In summary, our meta-analysis confirmed that hyperbaric oxygen therapy offers great benefits in the treatment of DFU and the reduction of amputation. In addition, larger and well-designed randomized controlled trials need to be planned and conducted to verify this conclusion.

Integrating Chinese and western medicine for COVID-19: A living evidence-based guideline (version 1).

BACKGROUND: The coronavirus disease 2019 (COVID-19) has turned into a pandemic and resulted in huge death tolls and burdens. Integrating Chinese and western medicine has played an important role in the fight against the COVID-19 pandemic. PURPOSE: We aimed to develop a living evidence-based guideline of integrating Chinese and western medicine for COVID-19. STUDY DESIGN: Living evidence-based guideline. METHODS: This living guideline was developed using internationally recognized and accepted guideline standards, dynamically monitoring the release of new clinical evidence, and quickly updating the linked living systematic review, evidence summary tables, and recommendations. Modified Delphi method was used to reach consensus for all recommendations. The certainty of the evidence, resources, and other factors were fully considered, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to rate the certainty of evidence and the strength of recommendations. RESULTS: The first version of this living guidance focuses on patients who are mild or moderate COVID-19. A multidisciplinary guideline development panel was established. Ten clinical questions were identified based on the status of evidence and a face-to-face experts' consensus. Finally, nine recommendations were reached consensus, and were formulated from systematic reviews of the benefits and harms, certainty of evidence, public accessibility, policy supports, feedback on proposed recommendations from multidisciplinary experts, and consensus meetings. CONCLUSION: This guideline panel made nine recommendations, which covered five traditional Chinese medicine (TCM) prescription granules/decoction (MXXFJD, QFPD, XFBD, TJQW, and JWDY), three Chinese patent medicines (LHQW granules/capsule, JHQG granules, and LHQK granules), and one Chinese herbal injection (XBJ injection). Of them, two were strongly recommended (LHQW granules/capsule and QFPD decoction), and five were weakly recommended (MXXFJD decoction, XFBD decoction, JHQG granules, TJQW granules, and JWDY decoction) for the treatment of mild and moderate COVID-19; two were weakly recommended against (XBJ injection and LHQK granules) the treatment of mild and moderate COVID-19. The users of this living guideline are most likely to be clinicians, patients, governments, ministries, and health administrators.

The characterization and candidate gene isolation for a novel male-sterile mutant ms40 in maize.

KEY MESSAGE: A novel genic male-sterile mutant ms40 was obtained from EMS treated RP125. The key candidate gene ZmbHLH51 located on chromosome 4 was identified by map-based cloning. This study further enriched the male sterile gene resources for both production applications and theoretical studies of abortion mechanisms. Maize male-sterile mutant 40 (ms40) was obtained from the progeny of the ethyl methanesulfonate (EMS) treated inbred line RP125. Genetic analysis indicated that the sterility was controlled by a single recessive nuclear gene. Cytological observation of anthers revealed that the cuticles of ms40 anthers were abnormal, and no Ubisch bodies were observed on the inner surface of ms40 anthers through scanning electron microscopy(SEM). Moreover, its tapetum exhibited delayed degradation and then blocked the formation of normal microspores. Using map-based cloning strategy, the ms40 locus was found to locate in a 282-kb interval on chromosome 4, and five annotated genes were predicted within this region. PCR-based sequencing detected a single non-synonymous SNP (G > A) that changed glycine (G) to arginine (A) in the seventh exon of Zm00001d053895, while no sequence difference between ms40 and RP125 was found for the other four genes. Zm00001d053895 encodes the bHLH transcription factor ZmbHLH51 which is localized in the nucleus. Phylogenetic analysis showed that ZmbHLH51 had the highest homology with Sb04g001650, a tapetum degeneration retardation (TDR) bHLH transcription factor in Sorghum bicolor. Co-expression analysis revealed a total of 1192 genes co-expressed with ZmbHLH51 in maize, 647 of which were anther-specific genes. qRT-PCR results suggested the expression levels of some known genes related to anther development were affected in ms40. In summary, these findings revealed the abortion characteristics of ms40 anthers and lay a foundation for further studies on the mechanisms of male fertility.

Gas-generating mesoporous silica nanoparticles with rapid localized drug release for enhanced chemophotothermal tumor therapy.

Chemophotothermal combination therapy has emerged as a novel and promising strategy to treat cancer. To improve anticancer effectiveness and reduce systemic toxicity, it is essential to trigger drug release at tumor sites or within tumor cells for maximal drug exposure. Herein, we constructed gas-generating mesoporous silica nanoparticles (MSNs) that can load ammonium bicarbonate (ABC) and doxorubicin (DOX) within the pores, encapsulate indocyanine green (ICG) onto the polydopamine (PDA) layer, and modify the RGD peptide on the outer surface [denoted as M(abc)-DOX@PDA-ICG-PEG-RGD] for triggered drug release and targeted chemophotothermal combination therapy. Upon hyperthermia or low pH value, the encapsulated ABC can efficiently generate CO2 gas, thus enhancing the damage to the PDA layer and accelerating DOX release. In vitro experiments showed that the M(abc)-DOX@PDA-ICG-PEG-RGD significantly enhanced cellular uptake and cytotoxicity, and laser irradiation further increased the endocytic and cytotoxic effects. An in vivo study indicated that the nanoparticles can effectively accumulate at the tumor site and significantly inhibited tumor growth with no side-effects to the normal organs. Thus, this gas-generating MSN-based nanocarrier that can trigger drug release in response to laser irradiation or low pH value holds great potential in enhancing cancer chemophotothermal combination therapy.

Manipulating energy migration within single lanthanide activator for switchable upconversion emissions towards bidirectional photoactivation.

Reliance on low tissue penetrating UV or visible light limits clinical applicability of phototherapy, necessitating use of deep tissue penetrating near-infrared (NIR) to visible light transducers like upconversion nanoparticles (UCNPs). While typical UCNPs produce multiple simultaneous emissions for unidirectional control of biological processes, programmable control requires orthogonal non-overlapping light emissions. These can be obtained through doping nanocrystals with multiple activator ions. However, this requires tedious synthesis and produces complicated multi-shell nanoparticles with a lack of control over emission profiles due to activator crosstalk. Herein, we explore cross-relaxation (CR), a non-radiative recombination pathway typically perceived as deleterious, to manipulate energy migration within the same lanthanide activator ion (Er3+) towards orthogonal red and green emissions, simply by adjusting excitation wavelength from 980 to 808 nm. These UCNPs allow programmable activation of two synergistic light-gated ion channels VChR1 and Jaws in the same cell to manipulate membrane polarization, demonstrated here for cardiac pacing.

A Dual-Model Imaging Theragnostic System Based on Mesoporous Silica Nanoparticles for Enhanced Cancer Phototherapy.

Mesoporous silica nanoparticles (MSNs) show great promise to be exploited as versatile multifunctional nanocarriers for effective cancer diagnosis and treatment. In this work, perfluorohexane (PFH)-encapsulated MSNs with indocyanine green (ICG)-polydopamine (PDA) layer and poly(ethylene glycol)-folic acid coating (designated as MSNs-PFH@PDA-ICG-PEG-FA) are successfully fabricated to achieve tumor ultrasonic (US)/near-infrared fluorescence (NIRF) imaging as well as photothermal therapy (PTT)/photodynamic therapy (PDT). MSNs-PFH@PDA-ICG-PEG-FA exhibits good monodispersity with high ICG loading, significantly enhances ICG photostability, and greatly improves cellular uptake. Upon single 808 nm NIR irradiation, the nanocarrier not only efficiently generates hyperthermia to realize PTT, but also produces reactive oxygen species (ROS) for effective PDT. Meanwhile, NIR irradiation can trigger PFH to undergo vaporization and provide a super-resolution US image. Thus, the PTT/PDT combination therapy can be dually guided by PFH-induced US imaging and ICG-induced NIRF imaging. In vivo antitumor studies demonstrate that PTT/PDT from MSNs-PFH@PDA-ICG-PEG-FA significantly inhibits tumor growth and achieves a cure rate of 60% (three out of five mice are completely cured). Hence, the multifunctional MSNs appear to be a promising theragnostic nanoplatform for multimodal cancer imaging and therapy.

Enhancement of Solasodine Extracted from Fruits of Solanum nigrum L. by Microwave-Assisted Aqueous Two-Phase Extraction and Analysis by High-Performance Liquid Chromatography.

Background: Solasodine is a major bioactive ingredient in Solanum nigrum L. that has strong pharmacological characteristics. Therefore, the development of a simple and effective extraction method for obtaining solasodine is highly important. This study aims to provide a rapid and effective method for extracting solasodine from Solanum nigrum L. by microwave-assisted aqueous two-phase extraction (MAATPE). Methods: First, the high-performance liquid chromatography (HPLC) conditions were established for the detection of solasodine. Then, the aqueous two-phase system (ATPS) compositions were examined. On the basis of the results of single-factor experiments, for a better yield, response surface methodology (RSM) was used to optimize influential factors including the extraction temperature, extraction time and liquid-to-solid ratio. Results: The maximum extraction yield of 7.11 ± 0.08 mg/g was obtained at 44 °C, an extraction time of 15 min, and a liquid-to-solid ratio of 42:1 mL/g in the ATPS consisting of EtOH solvent, (NH4)2SO4, and water (28:16:56, w/w/w). The extraction yield of the alkaloid obtained using this method was markedly higher than those of microwave-assisted extraction (MAE) and ultrasonic-assisted extraction (UAE). Conclusions: In this work, solasodine was extracted by MAATPE for the first time and a high yield was obtained. MAATPE is a simple, rapid, and green technique for extraction from medical plants. Thus, the present study will enable the development of a feasible extraction method of active alkaloids from Solanum nigrum L.