Moxibustion improves motor function by down-regulating SNX5 and inhibiting ferroptosis in neurons of corpus striatum in mice with Parkinson's disease. / 艾灸调控SNX5å¯¹å¸•é‡‘æ£®ç— æ¨¡åž‹å°é¼ ç¥žç»å ƒé“æ­»äº¡çš„å½±å“.

OBJECTIVES: To explore the effect of moxibustion on the expression of sorting nexin 5 (SNX5), glutathione peroxidase (GPX4) and ferritin heavy chain (FTH1) in the corpus striatum in mice with Parkinson's disease (PD), so as to explore its mechanisms underlying improvement of PD by ameliorating ferroptosis in the substantia nigra striatum. METHODS: C57BL/6J mice were randomly divided into normal, sham operation, model, and moxibustion groups, with 10 mice in each group. The PD model was established by unilateral injection of 6-hydroxydopamine (3.5 µL) into the right medial forebrain bundle (AP=-1.2 mm, ML=-1.3 mm, DV=-4.75 mm). The mice in the moxibustion group received moxibustion at "Baihui"(GV20) and "Sishencong"(EX-HN1) for 20 min each time, once a day, 6 times a week for 4 weeks. After the intervention, mice received apomorphine rotation behavior detection and pole climbing test. The expression of tyrosine hydroxylase (TH) in the substantia nigra was detected by immunofluorescence, the contents of Fe2+, malondialdehyde (MDA), the ratio of glutathione/oxidized glutathione (GSH/GSSG) in the corpus striatum were detected by using photocolorimetric method, and the expression levels of SNX5 (endocytosomal protein), GPX4 (one of the key targets for inhibiting ferroptosis) and FTH1 proteins and mRNAs in the corpus striatum were detected by Western blot and qPCR, respectively. RESULTS: Behavior tests showed that the pole climbing time and number of body rotation were significantly increased in the model group relevant to the sham operation group (P<0.01), and strikingly decreased in the moxibustion group relevant to the model group (P<0.01). The immunofluorescence intensity of TH in the substantia nigra, the ratio of GSH/GSSG, and the expression levels of GPX4 and FTH1 mRNAs and proteins in the corpus striatum were markedly decreased (P<0.01, P<0.05), while the contents of Fe2+ and MDA and the expression levels of SNX5 mRNA and protein in the corpus striatum significantly increased in the model group relevant to the sham operation group (P<0.01, P<0.05). Compared with the model group, the decreased immunofluorescence intensity of TH, GSH/GSSH, and the expression levels of GPX4 and FTH1 mRNAs and proteins, and the increased contents of Fe2+ and MDA and the expression levels of SNX5 mRNA and protein were reversed in the moxibustion group relevant to the model group (P<0.01, P<0.05). CONCLUSIONS: Moxibustion may improve motor dysfunction in PD mice, which may be related to its effects in down-regulating the expression of SNX5, promoting the synthesis of GSH, decreasing the contents of Fe2+ and MDA, up-regulating the ratio of GSH/GSSG and the expression of GPX4 and FTH1 mRNAs and proteins in the corpus striatum, and inhibiting the occurrence of ferroptosis.

Construction of high-density genetic map based on SLAF-seq and QTL analysis of major traits in sweetpotato [Ipomoea batatas (L.) Lam.].

Sweetpotato, Ipomoea batatas (L.) Lam., is an important worldwide crop used as feed, food, and fuel. However, its polyploidy, high heterozygosity and self-incompatibility makes it difficult to study its genetics and genomics. Longest vine length (LVL), yield per plant (YPP), dry matter content (DMC), starch content (SC), soluble sugar content (SSC), and carotenoid content (CC) are some of the major agronomic traits being used to evaluate sweetpotato. However limited research has actually examined how these traits are inherited. Therefore, after selecting 212 F1 from a Xin24 × Yushu10 crossing as the mapping population, this study applied specific-locus amplified fragment sequencing (SLAF-seq), at an average sequencing depth of 26.73 × (parents) and 52.25 × (progeny), to detect single nucleotide polymorphisms (SNPs). This approach generated an integrated genetic map of length 2441.56 cM and a mean distance of 0.51 cM between adjacent markers, encompassing 15 linkage groups (LGs). Based on the linkage map, 26 quantitative trait loci (QTLs), comprising six QTLs for LVL, six QTLs for YPP, ten QTLs for DMC, one QTL for SC, one QTL for SSC, and two QTLs for CC, were identified. Each of these QTLs explained 6.3-10% of the phenotypic variation. It is expected that the findings will be of benefit for marker-assisted breeding and gene cloning of sweetpotato.

Semi-synthesis and structure-activity relationship study yield antibacterial vicenistatin derivatives with low cytotoxicity.

Vicenistatin (1) is a 20-membered polyketide macrocyclic antibiotic with potent antimicrobial and cytotoxic activities. In this study, to further explore the potential of 1 as candidates of antibacterial drug development, 4'-N-demethyl vicenistatin (2), a secondary metabolite obtained from the ∆vicG mutant strain of Monodonata labio-associated Streptomyces parvus SCSIO Mla-L010, was utilized as a starting material for modifications of 4'-amino group of vicenistatin. Six new vicenistatin derivatives (3-8) were semi-synthesized through a concise route of amino modification with various aliphatic and aromatic aldehydes. Our study reveals that the bioactivity of vicenistatin is closely related to amino modification in sugar moiety, which results from the length of alkyl side chain as well as the presence of electron withdrawing/denoting group on the benzene ring. Importantly, compounds 4 with a butyl group and 8 with a 3,5-dihydroxyl-benzyl group at 4'-amino group, respectively, exhibited good antimicrobial activities, with MIC values spanning 0.5-4 µg ml-1 to Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, Micrococcus luteus and Bacillus subtilis, with low cytotoxicity. This research promotes the further exploration of structure-activity relationships of vicenistatin and provides new vicenistatin derivatives for development of future anti-infectious agents with reduced cytotoxicity.

Facile fluorescence detection of malachite green in fish using molecularly imprinted polymers doped CdTe quantum dots based system.

Malachite green (MG) possesses high toxicity, therefore, the detection of MG in fish tissues is of vital importance. A novel core-shell MIPs doped CdTe quantum dots coated silica nanoparticles (CdTe-MIP/SiO2 NPs) were synthesized via a simple one-pot strategy. The materials were characterized carefully. The resulting CdTe-MIP/SiO2 NPs were coated on the thin layer chromatography plate, and coupled with miniaturized fluorimeter for fluorescence detection of MG in fish samples. The resulting CdTe-MIP/SiO2 NPs based system possessed good linearity (0.01 âˆ¼ 20 µmol/L), high recoveries (98.36 %∼101.45 %) and low detection limit (3.7 nmol/L) for MG. Furthermore, CdTe-MIP/SiO2 NPs based system were employed to measure fish samples spiked with MG, meanwhile, HPLC was utilized to evaluate the accuracy and reliability. And the paired t-test was conducted to evaluate differences between fluorescence method and HPLC, P > 0.05 means no significant difference was observed, the results demonstrated that both fluorescence method and HPLC are suitable for MG analysis.

Investigating the Structure-property Relationships of Two Cd-based Hybrid Multifunctional Compounds with High Tc, Bright Fluorescence and Wide Band-gap.

Organic-inorganic hybrid multifunctional materials have shown significant application in lighting and sensor fields, owing to their prominent performance and diversity structures. Herein, we synthesized two multifunctional compounds: (propyl-quinuclidone)2 CdBr4 (1) and (F-butyl-quinuclidone)2 CdBr4 (2). By introducing light-emitting organic cation with flexible long chain, 1 and 2 exhibit excellent transition properties and bright blue-white fluorescence. Then, combine fluorescence lifetime and first-principal calculation, providing evidence for the electron transfer emission. Subsequently, investigated the impact of substituent carbon chain length (methyl to butyl), structural rigidity (C-C to C-F) and halide framework (Cl to I) on the fluorescence properties. Results indicate that Cd⋅⋅⋅Cd distance and structural rigidity play an important role in fluorescence. Overall, our research provides valuable insight and example for chemical modifications enhance compound performance.

Bioinspired fine-tuning of the mechanical rigidity of SNEDDS for the efficient crossing of multiple gastrointestinal barriers.

Nanoproperties, such as size, charge, and rigidity, have been demonstrated to be crucial for nanovehicles to overcome numerous gastrointestinal obstacles. However, the facile approach of modifying the rigidity of nanovehicles remains scarce, limiting understanding of how rigidity impacts their oral delivery. Inspired by the fact that cellular phospholipid content regulates plasma membrane rigidity, the rigidity of self-nanoemulsifiying drug delivery system (SNEDDS) could be fine-tuned via phosphocholine content while their size and zeta potential remain unchanged, using insulin as a model drug. Notably, soft SNEDDS exerted longer gastrointestinal transit time, higher drug release rate, stronger gastrointestinal stability and relatively lower mucus permeation but superior epithelial transcytosis than their hard counterparts in a macropinocytosis-dependent manner. The rigidity-related enhanced transcytosis was attributed to improved endocytosis, lysosome escape capability and exocytosis. Rats with type 1 diabetes exhibited greater oral insulin absorption and blood glucose lowering effect with soft SNEDDS. This study demonstrated the regulatory role of phospholipids in nanovehicle rigidity, which could help develop mechanically optimized nanomedicines in the future.

Moxibustion treatment for Parkinson's disease: study protocol for a randomized controlled trial.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder and seriously affects quality of life globally. Moxibustion is widely used to treat neurodegenerative diseases in the clinic and has achieved a beneficial clinical effect. However, strict control and high-quality randomized controlled trials are still lacking. Therefore, this trial aims to evaluate the clinical efficacy and safety of moxibustion in patients with PD and preliminarily explore the underlying mechanism. METHODS: This is a randomized, single-blind and placebo-controlled trial design in which 70 eligible participants will be randomly divided into a moxibustion group and a sham moxibustion group. Baihui (DU20) and Sishenchong (EX-HN1) are selected for both groups. The treatment will be performed for 30 min per session, two sessions a week for 8 weeks. The mean change in MDS-UPDRS scores (including MDS-UPDRS II, III subscale scores and total scores) from baseline to the observation points will be the primary outcome. The secondary outcomes will include scores on the Parkinson's Disease Questionnaire-39 (PDQ-39), Fatigue Severity Scale (FSS), Parkinson Disease Sleep Scale (PDSS), Montreal Cognitive Assessment (MoCA), and Self-Rating Depression Scale (SDS) as well as the Wexner constipation score. All the above outcomes will be assessed at 4 and 8 weeks. Laboratory blood biochemical analysis and functional magnetic resonance imaging (fMRI) will be conducted at baseline and at the end of treatment to explore the potential mechanisms of moxibustion in regulating PD. DISCUSSION: In conclusion, the results of this trial will reveal whether moxibustion is effective for treating motor and nonmotor symptoms in PD. This trial will also preliminarily explore the underlying mechanism of the regulatory effect of moxibustion in PD, which will contribute to providing a theoretical basis for the treatment of PD. TRIAL REGISTRATION: ClinicalTrials.gov ChiCTR2000029745. Registered on 9 August 2021.

High-Temperature Ferroelasticity and Photoluminescence in a 2D Monolayer Perovskite Compound: (C5NH8Br)2PbBr4.

Hybrid organic-inorganic perovskites (HOIPs) have attracted much attention due to their excellent properties and easy synthesis. As far as we know, most documented ferroelastics mainly focus on the 3D (three-dimensional) perovskites, the 2D monolayer perovskite ferroelastics are rarely reported before. In this work, we synthesized a 2D lead-based perovskite (C5NH13Br)2PbBr4 (1) (C5NH13Br = 5-bromoamylamine cation) by introducing flexible chain organic cations. The evolution of ferroelastic domains observed by a polarized light microscope confirms that compound 1 undergoes a ferroelastic phase transition at 392/384 K. In addition, its direct band gap is 2.877 eV. Interestingly, the material emits an attractive blue light (quantum yield 5.06%) under UV light. Three structural descriptors are introduced to quantitatively analyze the relationship between structural distortion and the shape of emission peak. This work provides a way to design multifunctional perovskite-type materials.

Six Sets of Aromatic Polyketides Differing in Size and Shape Derive from a Single Biosynthetic Gene Cluster.

One new aromatic polyketide, prealnumycin B (1), and four known aromatic polyketides, K1115A (2), 1,6-dihydroxy-8-propylanthraquinone (DHPA, 3), phaeochromycin B (4), and (R)-7-acetyl-3,6-dihydroxy-8-propyl-3,4dihydronaphthalen-1(2H)-one (5), were isolated from the marine-derived Streptomyces sundarbansensis SCSIO NS01; these compounds represent four sets of aromatic polyketides differing in size and shape. A type II polyketide synthase (PKS) cluster, als, was identified by complete genome sequencing and was shown, by in vivo gene inactivation experiments in the wild-type (WT) NS01 strain and heterologous expression experiments, to encode the biosynthesis of compounds 1-5. Moreover, heterologous expression of the als cluster afforded three additional aromatic polyketides representing two different carbon skeletons, the new phaeochromycin L (6) and two known aromatic polyketides, phaeochromycins D (7) and E (8). These findings expand our knowledge of type II PKS machineries and their versatility in generating structurally diverse aromatic polyketides and highlight the power of type II PKSs in accessing new polyketides via ectopic expression in heterologous hosts.

Resequencing of sweetpotato germplasm resources reveals key loci associated with multiple agronomic traits.

Sweetpotato is an important crop that exhibits hexaploidy and high heterozygosity, which limits gene mining for important agronomic traits. Here, 314 sweetpotato germplasm resources were deeply resequenced, and 4 599 509 SNPs and 846 654 InDels were generated, among which 196 124 SNPs were nonsynonymous and 9690 InDels were frameshifted. Based on the Indels, genome-wide marker primers were designed, and 3219 of 40 366 primer pairs were selected to construct the core InDel marker set. The molecular ID of 104 sweetpotato samples verified the availability of these primers. The sweetpotato population structures were then assessed through multiple approaches using SNPs, and diverse approaches demonstrated that population stratification was not obvious for most Chinese germplasm resources. As many as 20 important agronomic traits were evaluated, and a genome-wide association study was conducted on these traits. A total of 19 high-confidence loci were detected in both models. These loci included several candidate genes, such as IbMYB1, IbZEP1, and IbYABBY1, which might be involved in anthocyanin metabolism, carotenoid metabolism, and leaf morphogenesis, respectively. Among them, IbZEP1 and IbYABBY1 were first reported in sweetpotato. The variants in the promoter and the expression levels of IbZEP1 were significantly correlated with flesh color (orange or not orange) in sweetpotato. The expression levels of IbYABBY1 were also correlated with leaf shape. These results will assist in genetic and breeding studies in sweetpotato.

Dietary vitamin E intake and risk of Parkinson's disease: a cross-sectional study.

Objective: Current evidence on the association between dietary vitamin E intake and the risk of Parkinson's disease (PD) is limited. The aim of the study was to explore the association of dietary vitamin E intake with PD in the United States among adults over 40 years. Methods: We conducted a cross-sectional study with data collected from National Health and Nutrition Examination Survey (NHANES) from 2009 to 2018. A total of the sample of 13,340 participants were included. To identify the different characteristics of the participants, we utilized propensity score matching (PSM) to reduce the effects of selection bias and confounding variables. Weighted univariate and multivariable logistic regression were used to examine the association between dietary vitamin E intake and PD before and after matching. Then, restricted cubic spline (RCS) was used to visually describe the possible non-linear relationships. Finally, we employed the subgroup analysis to further investigate the relationship between dietary vitamin E intake and PD. Results: According to the weighted univariate and multivariable logistic regression analysis, vitamin E intake was inversely associated with the risk of PD before and after matching. The results of RCS analysis revealed no non-linear inverse relationship between vitamin E intake and PD before and after matching. The subgroup analysis showed that age may influence the negative association between vitamin E and PD (P < 0.05 for interaction). Conclusion: Among participants over 40 years of age, vitamin E intake was negatively associated with the risk of PD. Our data may support the supplementation of vitamin E to be used as an intervention strategy for the occurrence of PD.

Characterization of the Glycosyltransferase and Methyltransferase Encoded Remotely from the Actinopyrone Biosynthetic Gene Cluster Enables Access to Diverse Analogues.

The actinopyrone biosynthetic gene cluster (atpn) lacks glycosyl- and methyltransferase genes, yet its product clearly calls for such enzymes. Using bioinformatics and biochemical methods, we confirmed that the mt3913 and gt723 genes, well beyond the atpn cluster boundaries, encode methyltransferase and glycosyltransferase, respectively. Moreover, homologous protein GT1507 enabled us to produce 14 non-natural actinopyrone analogues. PM050463 (3) was found to display potent anti-Helicobacter pylori activity and no signs of cytotoxicity.

Effect of acupuncture for non-motor symptoms in patients with Parkinson's disease: A systematic review and meta-analysis.

Background: Although non-motor symptoms of Parkinson's disease (PD) are serious, effective treatments are still lacking. Acupuncture may have clinical benefits for non-motor symptoms of PD patients, but high-quality evidence supporting this possibility is still limited. Hence, we conducted this meta-analysis to evaluate the effect of acupuncture treatment on non-motor symptoms in patients with PD. Methods: Randomized controlled trials (RCTs) of acupuncture treatment for PD were retrieved from the following electronic databases: Medline (OVID), Embase (OVID), Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese BioMedical Literature Database, Chonqing VIP (CQVIP), and Wangfang database. Studies evaluating non-motor symptoms of PD were retrieved. Methodological quality was assessed using the Cochrane Handbook for Systematic Reviews of Interventions. Results: A total of 27 RCTs were included, among which 8 outcomes related to non-motor symptoms were evaluated. The results showed that acupuncture combined with medication had benefits for PD-related insomnia relative to medication alone or sham acupuncture [standardized mean difference (SMD) = 0.517; 95% confidence interval (CI) = 0.242-0.793; p = 0.000], and acupuncture treatment had benefits at 8 weeks (SMD = 0.519; 95% CI = 0.181-0.857; p = 0.003). Regarding depression, acupuncture treatment was more effective (SMD = -0.353; 95% CI = -0.669 to -0.037; p = 0.029) within 2 months (SMD = -0.671; 95% CI = -1.332 to -0.011; p = 0.046). Regarding cognition, quality of life, and Unified Parkinson's Disease Rating Scale (UPDRS) I and II scores, acupuncture treatment was effective [SMD = 0.878, 95% CI = 0.046-1.711, p = 0.039; SMD = -0.690, 95% CI = -1.226 to -0.155, p = 0.011; weighted mean difference (WMD) = -1.536, 95% CI = -2.201 to -0.871, p = 0.000; WMD = -2.071, 95% CI = -3.792 to -0.351, p = 0.018; respectively]. A significant difference was not found in terms of PD-related constipation. Only one study evaluated PD-related fatigue. Conclusion: The results of the analysis suggested that acupuncture treatment could ameliorate the symptoms of depression, quality of life, cognition, total mentation, behavior and mood, and activities of daily living in PD patients. Nevertheless, more prospective, well-designed RCTs with larger sample sizes are required to confirm our findings.

Liquid-Liquid Phase Separation Promotes Protein Aggregation and Its Implications in Ferroptosis in Parkinson's Disease Dementia.

The pathological features of PDD are represented by dopaminergic neuronal death and intracellular α-synuclein (α-syn) aggregation. The interaction of iron accumulation with α-syn and tau was further explored as an essential pathological mechanism of PDD. However, the links and mechanisms between these factors remain unclear. Studies have shown that the occurrence and development of neurodegenerative diseases such as PDD are closely related to the separation of abnormal phases. Substances such as proteins can form droplets through liquid-liquid phase separation (LLPS) under normal physiological conditions and even undergo further liquid-solid phase transitions to form solid aggregates under disease or regulatory disorders, leading to pathological phenomena. By analyzing the existing literature, we propose that LLPS is the crucial mechanism causing abnormal accumulation of α-syn, tau, and other proteins in PDD, and its interaction with iron metabolism disorder is the key factor driving ferroptosis in PDD. Therefore, we believe that LLPS can serve as one of the means to explain the pathological mechanism of PDD. Determining the significance of LLPS in neurodegenerative diseases such as PDD will stimulate interest in research into treatments based on interference with abnormal LLPS.

MGCEP 1.0: A Genetic-Engineered Marine-Derived Chassis Cell for a Scaled Heterologous Expression Platform of Microbial Bioactive Metabolites.

Marine microorganisms produce a variety of bioactive secondary metabolites, which represent a significant source of novel antibiotics. Heterologous expression is a valuable tool for discovering marine microbial secondary metabolites; however, marine-derived chassis cell is very scarce. Here, we build an efficient plug-and-play marine-derived gene clusters expression platform 1.0 (MGCEP 1.0) by the systematic engineering of the deep-sea-derived Streptomyces atratus SCSIO ZH16. For a proof of concept, four families of microbial bioactive metabolite biosynthetic gene clusters (BGCs), including alkaloids, aminonucleosides, nonribosomal peptides, and polyketides, were efficiently expressed in this platform. Moreover, 19 compounds, including two new angucycline antibiotics, were produced in MGCEP 1.0. Dynamic patterns of global biosynthetic gene expression in MGCEP 1.0 with or without a heterologous gene cluster were revealed at the transcriptome level. The platform MGCEP 1.0 provides new possibilities for expressing microbial secondary metabolites, especially of marine origin.

Comparison of Improved Surgical Eight-Step Handwashing Combined with ATP Fluorescence in Detecting the Infection Rate at the Site of Seven-Step Surgical Handwashing and 30-Day Orthopaedic Surgery: A Randomized Study.

Objectives: To compare the effects of two hand cleaning schemes on the prevention of surgical site infection in routine orthopaedic surgery. Compared with the standard surgical seven-step washing technique and detected by ATP fluorescence method, the handwashing effects of the improved surgical eight-step washing technique and the standard surgical seven-step washing technique were compared, so as to provide a basis for eliminating the handwashing blind area of the surgical seven step washing technique and improving the surgical handwashing method. Methods: A total of 800 consecutive patients who underwent clean and clean-contaminated orthopaedic surgery between January 1, 2020 and December 31, 2020. Twenty orthopaedic doctors in the operating room of our research team were randomly divided into the improved eight-step washing technique group (improved group) and the traditional seven-step washing technique group (traditional group), with 10 people in each group. Each person was randomly sampled 40 times, 400 people in each group, a total of 800 people, and completed by stages in 12 months. Main Outcome Measures. The infection rate of surgical site 30 days after operation was the primary end point. The qualified rate of fingertip culture was combined with ATP fluorescence in the two groups and three new culture areas in the two groups: the lateral edge of the palm, the medial edge of the palm, and the nail groove of the middle finger and the nail root were secondary end points. Results: The 2 protocols were comparable in regard to surgical site infection risk factors. The infection rate of surgical site in the traditional group was 10 cases (2.50%) in 400 cases and 0 cases (0%) in the improved group. Three culture areas were added: the qualified rate of lateral edge of palm, medial edge of palm, and nail groove and nail root of middle finger, and the nosocomial infection rate of surgical incision between the two groups was statistically significant (P < 0.05). There was no significant difference in the qualified rate of fingertip culture (P > 0.05). The handwashing scheme in this study meets the recommended duration of hand disinfection and has good tolerance, and the skin dryness and skin irritation after using aqueous solution are similar. Conclusions: The improved surgical eight-step washing technique combined with ATP fluorescence detection is helpful to eliminate the "blind area" of handwashing. It is also necessary to add three training areas. Handwashing and training are more scientific, rigorous, and effective. They are effective in reducing orthopaedic surgical infection and have application value. They can safely replace the traditional surgical seven-step washing technique, which is worthy of clinical promotion.

Metabolic Blockade-Based Genome Mining Reveals Lipochain-Linked Dihydro-ß-alanine Synthetases Involved in Autucedine Biosynthesis.

Continuously mining the Streptomyces olivaceus SCSIO T05 genome leads to the identification of new lipopeptides (autucedines A-C), constituting members of the 10th skeleton isolated from this strain. The corresponding biosynthetic gene cluster (aut) was verified by heterogeneous expression, and another two analogues (autucedines D and E) were isolated from the heterogeneous expression strain. Gene inactivation experiments revealed that construction of the unique "lipochain-linked dihydro-ß-alanine" unit takes place prior to the NRPS assembly line.

Streptomyces marincola sp. nov., a Novel Marine Actinomycete, and Its Biosynthetic Potential of Bioactive Natural Products.

Marine actinomycetes are an important source of antibiotics, but many of them are yet to be explored in terms of taxonomy, ecology, and functional activity. In this study, two marine actinobacterial strains, designated SCSIO 64649T and SCSIO 03032, were isolated, and the potential for bioactive natural product discovery was evaluated based on genome mining, compound detection, and antimicrobial activity. Phylogenetic analysis of the 16S rRNA gene sequences showed that strain SCSIO 64649T formed a single clade with SCSIO 03032 (similarity 99.5%) and sister clades with the species Streptomyces specialis DSM 41924T (97.1%) and Streptomyces manganisoli MK44T (96.8%). The whole genome size of strain SCSIO 64649T was 6.63 Mbp with a 73.6% G + C content. The average nucleotide identity and digital DNA-DNA hybridization between strain SCSIO 64649T and its closest related species were well below the thresholds recommended for species delineation. Therefore, according to the results of polyphasic taxonomy analysis, the strains SCSIO 64649T and SCSIO 03032 are proposed to represent a novel species named Streptomyces marincola sp. nov. Furthermore, strains SCSIO 64649T and 03032 encode 37 putative biosynthetic gene clusters, and in silico analysis revealed that this new species has a high potential to produce unique natural products, such as a novel polyene polyketide compounds, two mayamycin analogs, and a series of post-translationally modified peptides. In addition, other important bioactive natural products, such as heronamide F, piericidin A1, and spiroindimicin A, were also detected in strain SCSIO 64649T. Finally, this new species' metabolic crude extract showed a strong antimicrobial activity. Thanks to the integration of all these analyses, this study demonstrates that the novel species Streptomyces marincola has a unique and novel secondary metabolite biosynthetic potential that not only is beneficial to possible marine hosts but that could also be exploited for industrial applications.

[FU Wen-bin's experience in treatment of depression complicated with obsessive-compulsive disorder from perspective of heart and gallbladder].

Based on the thinking of integrative and holistic acupuncture and moxibustion, FU Wen -bin proposes to treat depression complicated with obsessive-compulsive disorder from perspective of heart and gallbladder. In clinical practice, the treatment pattern of "acupuncture at the top priority, followed by moxibustion, and consolidation at the end" is applied, acupuncture, refined moxibustion, intradermal needle and other therapies are comprehensively adopted, acupoints on the heart meridian, pericardium meridian and gallbladder meridian are selected or back-shu points and front-mu points of the heart, gallbladder and pericardium are matched, and the acupoints on the conception vessel and governor vessel and with the functions of tonifying kidney and regulating qi are added to calm the heart and tranquilize the mind, so as the symptoms of depression and obsessive-compulsive can be effectively relieved.

Characterization of the Aminosugar Biosynthetic and Regulatory Genes of Vicenistatin in Monodonata labio-Associated Streptomyces parvus SCSIO Mla-L010.

Vicenistatin (1) is a potent polyketide antitumor antibiotic composed of a 20-membered macrolactam core appended to a unique aminosugar, vicenisamine. In this study, vicenistatin was isolated and its biosynthetic gene cluster identified from Monodonata labio-associated Streptomyces parvus SCSIO Mla-L010. A set of five genes, vicC, vicD, vicE, vicF, and vicG, was confirmed to be involved in the biosynthesis of the aminosugar by gene inactivations. VicG was characterized as an N-methyltransferase that catalyzes the methylation of the 4'-amino group in the last step of the aminosugar biosynthetic pathway; the N-demethyl intermediate 4'-N-demethylvicenistatin (2) was isolated from the ΔvicG mutant strain. In addition, vicR1 was characterized as a positive pathway-specific regulatory gene. Notably, N-demethyl compound 2 was found to exert impressive antibacterial activities, with MIC values spanning 0.06-4 µg/mL, against a panel of Gram-positive bacteria including methicillin-resistant Staphylococcus aureus, Gram-negative Helicobacter pylori, and mycobacterium Mycobacterium smegmatis and the fungal pathogen Candida albicans. Compound 2 was also found to display reduced cytotoxicities relative to vicenistatin, especially against noncancerous human cell lines.