4.4 kW Nd:YAG slab amplifier with a high repetition frequency and high beam quality.

Using the self-developed fused indium wetting technology and planar waveguide, the uniform heat dissipation of the slab crystal and uniform pumping of the pump light were achieved, respectively. Based on the master oscillator power amplification (MOPA) scheme, the power was then amplified when the seed light source passed through the Nd:YAG slab crystal three times. Additionally, the image transfer system that we added to the amplified optical path achieved high beam quality. Finally, we obtained a rectangular pulsed laser with an output average power of 4461 W, a repetition frequency of 20 kHz, a pulse width of 62 ns, an optical-to-optical conversion efficiency of 26.8%, and a beam quality of ß x=7.0 and ß y=7.7.

Recognition on pharmacodynamic ingredients of natural products.

Natural products (NPs) play an irreplaceable role in the intervention of various diseases and have been considered a critical source of drug development. Many new pharmacodynamic compounds with potential clinical applications have recently been derived from NPs. These compounds range from small molecules to polysaccharides, polypeptides, proteins, self-assembled nanoparticles, and extracellular vesicles. This review summarizes various active substances found in NPs. The investigation of active substances in NPs can potentiate new drug development and promote the in-depth comprehension of the mechanism of action of NPs that can be beneficial in the prevention and treatment of human diseases.

Transcutaneous Electrical Acupoints Stimulation Improves Spontaneous Voiding Recovery After Laparoscopic Cholecystectomy: A Randomized Clinical Trial.

BACKGROUND: Facilitating the recurrence of spontaneous voiding is considered to be a way to prevent urinary retention after surgery, which is of great importance in cholecystectomy. This study aimed to assess the effect of transcutaneous electrical acupoint stimulation (TEAS) on spontaneous voiding recovery after laparoscopic cholecystectom. METHODS: Participants who underwent elective laparoscopic cholecystectomy were randomly assigned to either the TEAS group or the sham group. Active TEAS or sham TEAS at specific acupuncture points was conducted intraoperatively and postoperatively. The primary outcome was the recovery speed of spontaneous voiding ability after surgery and secondary outcomes included postoperative urinary retention (POUR), voiding dysfunction, pain, anxiety and depression, and early recovery after surgery. RESULTS: A total of 1,948 participants were recruited and randomized to TEAS (n = 975) or sham (n = 973) between August 2018 and June 2020. TEAS shortens the time delay of the first spontaneous voiding after laparoscopic cholecystectomy (5.6 h [IQR, 3.7-8.1 h] in the TEAS group vs 7.0 h [IQR, 4.7-9.7 h] in the sham group) (p < 0.001). The TEAS group experienced less POUR (p = 0.020), less voiding difficulty (p < 0.001), less anxiety and depression (p < 0.001), reduced pain (p = 0.007), and earlier ambulation (p = 0.01) than the sham group. CONCLUSIONS: Our results showed that TEAS is an effective approach to accelerate the recovery of spontaneous voiding and reduce POUR which facilitates recovery for patients after laparoscopic cholecystectomy.

Electroacupuncture Relieves Hippocampal Injury by Heme Oxygenase-1 to Improve Mitochondrial Function.

INTRODUCTION: Electroacupuncture (EA) treatment has been demonstrated to have the potential to prevent sepsis-induced hippocampal injury; however, the mechanisms underlying the protective effects of EA against such injury remain unclear. Herein, to elucidate these mechanisms, we constructed a mouse model of lipopolysaccharide (LPS)-induced hippocampal injury to investigate the protection mechanism of EA and to determine whether heme oxygenase-1 (HO-1)-mediated mitochondrial function is involved in the protective effect of EA. MATERIALS AND METHODS: The sepsis model of hippocampal injury was induced by administering LPS. The Zusanli and Baihui acupoints were stimulated using EA for 30 min once a day, for 5 d before LPS exposure and the first day after administering LPS. Hippocampal injury was investigated by hematoxylin and eosin staining and Nissl staining. HO-1 levels were measured using Western blotting. Mitochondrial metabolism was validated by assessing adenosine triphosphate, superoxide dismutase, malondialdehyde levels, reactive oxygen species production, and mitochondrial respiratory chain activity. Mitochondrial morphology was analyzed by transmission electron microscopy. RESULTS: EA treatment alleviated neuronal injury, impeded oxidative stress, and improved mitochondrial respiratory function, energy metabolism, and mitochondrial morphology in LPS-exposed mice. In addition, HO-1 knockout aggravated LPS-induced hippocampal injury, aggravated oxidative stress, and reduced mitochondrial respiratory function and aggravated mitochondrial swelling, crest relaxation, and vacuole degeneration. Moreover, EA was unable to reverse the hippocampal damage and mitochondrial dysfunction caused by LPS exposure after HO-1 knockout. CONCLUSIONS: EA improves LPS-induced hippocampal injury by regulating HO-1-mediated mitochondrial function. Furthermore, HO-1 plays a critical role in maintaining mitochondrial function and resisting oxidative injury.

[Optical voltage imaging in neurons in neurogenic erectile dysfunction: Progress in research].

Optical voltage imaging in neurons is a popular technology in the study of neural electrophysiology, which has been applied in many disciplines, including neurological, gastrointestinal and cardio-cerebrovascular sciences and mental health. However, few reports are seen on its application in the study of neurogenic ED. This article presents an overview of neuronal optical voltage imaging in the study of neurological ED, including its development, classification, technical theories and the possibility of its application in neurological ED research, hoping to provide some new ideas for researchers in the related fields.

Chiral phosphoric acid-catalyzed asymmetric dearomatization reactions.

We summarize in this review the recent development of chiral phosphoric acid (CPA)-catalyzed asymmetric dearomatization reactions. A wide array of electron-rich arenes (indoles, phenols, naphthols, benzothiophenes, benzofurans, etc.) and electron-poor arenes (pyridines, quinolines, isoquinolines, etc.) has been proved reactive towards various reaction partners in the presence of a CPA catalyst, enabling asymmetric dearomatization reactions that lead to structurally-diverse polycyclic molecules. The reactions are grouped according to the roles of the arenes in the reactions (as nucleophiles or electrophiles) and the types of reaction partners. This review closes with a personal perspective on the dynamic research area of asymmetric dearomatization reactions by CPAs.

Manipulation of Spiroindolenine Intermediates for Enantioselective Synthesis of 3-(Indol-3-yl)-Pyrrolidines.

By manipulating the reactivity of spiroindolenine species, a sequential Michael/retro-Mannich/Mannich reaction of ω-indol-3-yl α,ß-unsaturated ketones was developed. In the presence of 10 mol % of a chiral phosphoric acid as the catalyst, a series of 3-(indol-3-yl)-pyrrolidines were synthesized in high yields (up to 91 %) with excellent stereoselectivities (up to 92 % ee, >19:1 d.r.). The products obtained here undergo diverse functional-group transformations. The mechanistic proposal of this reaction is supported by DFT calculations.

Highly Substituted Benzophenone Aldehydes and Eremophilane Derivatives from the Deep-Sea Derived Fungus Phomopsis lithocarpus FS508.

Five new benzophenone derivatives named tenellones D⁻H (1⁻5), sharing a rare naturally occurring aldehyde functionality in this family, and a new eremophilane derivative named lithocarin A (7), together with two known compounds (6 and 8), were isolated from the deep marine sediment-derived fungus Phomopsis lithocarpus FS508. All of the structures for these new compounds were fully characterized and established on the basis of extensive spectroscopic interpretation and X-ray crystallographic analysis. Compound 5 exhibited cytotoxic activity against HepG-2 and A549 cell lines with IC50 values of 16.0 and 17.6 µM, respectively.

Catalytic Asymmetric Dearomatization of Indolyl Dihydropyridines through an Enamine Isomerization/Spirocyclization/Transfer Hydrogenation Sequence.

A highly efficient synthesis of enantioenriched spiroindolines by catalytic asymmetric dearomatization of indolyl dihydropyridines through a chiral phosphoric acid catalyzed enamine isomerization/spirocyclization/transfer hydrogenation sequence has been developed. This reaction proceeds under mild reaction conditions, affording novel spiroindolines in good yields (up to 88 %) with excellent enantioselectivity (up to 97 % ee). DFT calculations provide insights into the reaction mechanism as well as the origin of stereochemistry.

[Effect of Shirexiao waist hot-compress on the expressions of Th17/Treg-specific factors in the mouse model of experimental autoimmune prostatitis with damp heat syndrome].

OBJECTIVE: To investigate the effect of waist hot-compress with the Shirexiao (SRX) pad on the expressions of Th17/Treg-specific factors in the prostatic tissue of the mouse model of experimental autoimmune prostatitis (EAP) with damp heat syndrome, and explore its possible action mechanisms. METHODS: Twenty healthy male mice were included as normal controls and another 100 chosen for establishing the model of EAP with damp heat syndrome by subcutaneous injection of purified prostate protein solution from the Wistar rat and Freund's complete adjuvant using the TCM method. The model mice were randomly divided into five groups: model control, matrix, and low-, medium- and high-dose SRX. After chemical removal of the hair at lumbar vertebrae 1－3, the animals of the low-, medium- and high-dose SRX groups were treated with the SRX pad heated to 45℃ and externally applied to the non-hair area, qd, bid, and tid, respectively, 10 minutes each time, those of the matrix group with the vaseline pad, and those of the normal and model control groups with the saline pad. After 4 weeks of continuous treatment, all the mice were sacrificed for determination of the protein and mRNA expressions of RORγt and Foxp3 in the prostate tissue by Western blot and quantitative real-time PCR. RESULTS: The symptoms, signs and pathological changes of the EAP model mice were similar to the manifestations of chronic prostatitis. After intervention, the protein and mRNA expressions of Foxp3 were significantly down-regulated while those of RORγt markedly up-regulated in the EAP model group as compared with the normal control (P <0.05). In comparison with the model controls, the protein and mRNA expressions of RORγt were remarkably decreased in the medium- and high-dose SRX groups (P <0.05), that of the Foxp3 protein was markedly increased in the high-dose group (P <0.05), while that of Foxp3 mRNA exhibited no statistically significant difference in the low-, medium- or high-dose groups (P >0.05). CONCLUSIONS: The Shirexiao waist hot-compress therapy plays a positive role in the treatment of autoimmune prostatitis with damp heat syndrome by reducing the expression of RORγt, inhibiting the differentiation of Th17 and thus checking the differentiation imbalance of Th17/Treg.

Construction of Chiral Tetrahydro-ß-Carbolines: Asymmetric Pictet-Spengler Reaction of Indolyl Dihydropyridines.

A highly efficient synthesis of the enantioenriched tetrahydro-ß-carbolines was developed by using a chiral phosphoric acid catalyzed Pictet-Spengler reaction of indolyl dihydropyridines. The reaction proceeds under mild reaction conditions to afford the desired chiral tetrahydro-ß-carbolines in good to excellent yields (up to 96 %) and high enantioselectivities (up to 99 % ee). With this method, a formal synthesis of tangutorine and a total synthesis of deplancheine were achieved in a highly efficient manner.

Analysis of cardiovascular function in diabetic patients using EEMD-ICA fusion multi-scale percussion entropy.

BACKGROUND: Diabetes is a chronic disease that can lead to a variety of complications and even cause death. The signal characteristics of the photoplethysmography signals (PPG) and electrocardiogram signals (ECG) can reflect the autonomic and vascular aspects of the effects of diabetes on the body. OBJECTIVE: Based on the complex mechanism of interaction between PPG and ECG, a set of ensemble empirical mode decomposition-independent component analysis (EEMD-ICA) fusion multi-scale percussion entropy index (MSPEI) method was proposed to analyze cardiovascular function in diabetic patients. METHODS: Firstly, the original signal was decomposed into multiple Intrinsic Mode Function (IMFs) by ensemble empirical mode decomposition EEMD, principal components of IMF were extracted by independent component analysis (ICA), then the extracted principal components were reconstructed to eliminate the complex high and low frequency noise of physiological signals. In addition, the MSPEI was calculated for the ECG R-R interval and PPG amplitude sequence.(RRI and Amp) The results showed that, compared with EEMD method, the SNR of EEMD-ICA method increases from 2.1551 to 11.3642, and the root mean square error (RMSE) decreases from 0.0556 to 0.0067. This algorithm can improve the performance of denoising and retain more feature information. The large and small scale entropy of MSPEI (RRI,Amp) was significantly different between healthy and diabetic patients (p< 0.01). RESULTS: Compared with arteriosclerosis index (AI) and multi-scale cross-approximate entropy (MCAE): MSPEISS (RRI,Amp) indicated that diabetes can affect the activity of human autonomic nervous system, while MSPEILS (RRI,Amp) indicated that diabetes can cause or worsen arteriosclerosis. CONCLUSION: Multi-scale Percussion Entropy algorithm has more advantages in analyzing the influence of diabetes on human cardiovascular and autonomic nervous function.

Lipidomic and transcriptomic analysis of the increase in eicosapentaenoic acid under cobalamin deficiency of Schizochytrium sp.

Schizochytrium sp. is a heterotrophic microorganism capable of accumulating polyunsaturated fatty acids and has achieved industrial production of docosahexaenoic acid (DHA). It also has the potential for eicosapentaenoic acid (EPA) production. In this study, it was found that the cell growth, lipid synthesis and fatty acid composition of Schizochytrium sp. were significantly affected by the level of cobalamin in the medium, especially with regard to the content of EPA in the fatty acids. The content of EPA in the fatty acids increased 17.91 times, reaching 12.00%, but cell growth and lipid synthesis were significantly inhibited under cobalamin deficiency. The response mechanism for this phenomenon was revealed through combined lipidomic and transcriptomic analysis. Although cell growth was inhibited under cobalamin deficiency, the genes encoding key enzymes in central carbon metabolism were still up-regulated to provide precursors (Acetyl-CoA) and reducing power (NADPH) for the synthesis and accumulation of fatty acids. Moreover, the main lipid subclasses observed during cobalamin deficiency were glycerolipids (including glycerophospholipids), with EPA primarily distributed in them. The genes involved in the biosynthesis of these lipid subclasses were significantly up-regulated, such as the key enzymes in the Kennedy pathway for the synthesis of triglycerides. Thus, this study provided insights into the specific response of Schizochytrium sp. to cobalamin deficiency and identified a subset of new genes that can be engineered for modification.

Innovative Delivery System Combining CRISPR-Cas12f for Combatting Antimicrobial Resistance in Gram-Negative Bacteria.

Antimicrobial resistance poses a significant global challenge, demanding innovative approaches, such as the CRISPR-Cas-mediated resistance plasmid or gene-curing system, to effectively combat this urgent crisis. To enable successful curing of antimicrobial genes or plasmids through CRISPR-Cas technology, the development of an efficient broad-host-range delivery system is paramount. In this study, we have successfully designed and constructed a novel functional gene delivery plasmid, pQ-mini, utilizing the backbone of a broad-host-range Inc.Q plasmid. Moreover, we have integrated the CRISPR-Cas12f system into the pQ-mini plasmid to enable gene-curing in broad-host of bacteria. Our findings demonstrate that pQ-mini facilitates the highly efficient transfer of genetic elements to diverse bacteria, particularly in various species in the order of Enterobacterales, exhibiting a broader host range and superior conjugation efficiency compared to the commonly used pMB1-like plasmid. Notably, pQ-mini effectively delivers the CRISPR-Cas12f system to antimicrobial-resistant strains, resulting in remarkable curing efficiencies for plasmid-borne mcr-1 or blaKPC genes that are comparable to those achieved by the previously reported pCasCure system. In conclusion, our study successfully establishes and optimizes pQ-mini as a broad-host-range functional gene delivery vector. Furthermore, in combination with the CRISPR-Cas system, pQ-mini demonstrates its potential for broad-host delivery, highlighting its promising role as a novel antimicrobial tool against the growing threat of antimicrobial resistance.

Jatropholane-type diterpenes from Euphorbia sikkimensis.

Four new jatropholane-type diterpenes (1-4), named sikkimenoids A-D, were isolated from the aerial parts of Euphorbia sikkimensis. The structural elucidations of 1-4 were accomplished by extensive NMR analyses, and their absolute configurations were established by ECD calculations. Compound 2 exhibited weak antiangiogenic activity with an IC(50) value of 43.0 µM when evaluated using a zebrafish model.

[Study on the chemical constituents of Gastrodia elata].

OBJECTIVE: To study the chemical constituents of Gastrodia elata. METHODS: The compounds were isolated by silica gel column chromatography and recrystallization and their structures were elucidated by spectral analysis. RESULTS: The structures of 14 compounds were identified as: p-hydroxybenzyl alcohol (1), p-hydroxybenzaldehyde (2), 3, 4-dihydroxybenzaldehyde (3), 4, 4'-dihydroxy, dibenzyl ether (4), 4-hydroxymethyl benzyl-4'-hydroxy-3'-(4"-hydroxy benzl) benzyl ether (5), 4-ethoxybenzyl alcohol (6), anisic alcohol (7), bis(3, 4-dihydroxyphenyl) methane (8), 4, 4'-dihydroxydiphenyl methane (9), 2, 4-bis(4'-hydroxy-benzyl)-phenol (10), 4-( methoxymenthyl) benzene-1, 2-diol (11), p-methylphenyl-1 -O-beta-D-glucopyranoside (12), N6-(4'-hydroxybenzl) -adenosine (13) and beta-sitosterol (14). CONCLUSION: Compounds 6 - 8 and 11 are isolated from this plant for the first time.

Development of a green fermentation strategy with resource cycle for the docosahexaenoic acid production by Schizochytrium sp.

The fermentation production of docosahexaenoic acid (DHA) is an industrial process with huge consumption of freshwater resource and nutrient, such as carbon sources and nitrogen sources. In this study, seawater and fermentation wastewater were introduced into the fermentation production of DHA, which could solve the problem of fermentation industry competing with humans for freshwater. In addition, a green fermentation strategy with pH control using waste ammonia, NaOH and citric acid as well as FW recycling was proposed. It could provide a stable external environment for cell growth and lipid synthesis while alleviating the dependence on organic nitrogen sources of Schizochytrium sp. It was proved that this strategy has good industrialization potential for DHA production, and the biomass, lipid and DHA yield reached to 195.8 g/L, 74.4 g/L and 46.4 g/L in 50 L bioreactor, respectively. This study provides a green and economic bioprocess technology for DHA production by Schizochytrium sp.

Compatibility of Polygonati Rhizoma and Angelicae Sinensis Radix enhance the alleviation of metabolic dysfunction-associated fatty liver disease by promoting fatty acid ß-oxidation.

Jiuzhuan Huangjing Pills (JHP) composed of Polygonati Rhizoma (PR) and Angelicae Sinensis Radix (ASR) remedied mitochondria to cure metabolic dysfunction-associated fatty liver disease (MAFLD). However, a comparison of the anti-MAFLD ability between JHP prescription and PR and ASR single-medicines in MAFLD has not been performed, and the action mechanisms and substances remain unknown. Our results show that JHP, PR and ASR decreased serum and liver lipid levels. The effects of JHP were stronger than those of PR and ASR. JHP, PR and ASR afforded protection to mitochondrial ultrastructure, and regulated oxidative stress and energy metabolism in mitochondria. JHP also regulated the expression of ß-oxidation genes, which were not regulated by PR and ASR. JHP-, PR- and ASR-derived components in mitochondrial extracts regulated oxidative stress, energy metabolism, and ß-oxidation gene expression and alleviated cellular steatosis. Four, six and eleven compounds were identified in mitochondrial extracts from PR-, ASR- and JHP-treated rats, respectively. The data suggest that JHP, PR and ASR alleviated MAFLD by remedying mitochondria, while the ability of JHP was stronger than that of PR and ASR, which was involved with the ß-oxidation promotion. The compounds identified may be the main ingredients in the three extracts active in MAFLD improvement.