Free-electron lasing at 27 nanometres based on a laser wakefield accelerator.

X-ray free-electron lasers can generate intense and coherent radiation at wavelengths down to the sub-ångström region1-5, and have become indispensable tools for applications in structural biology and chemistry, among other disciplines6. Several X-ray free-electron laser facilities are in operation2-5; however, their requirement for large, high-cost, state-of-the-art radio-frequency accelerators has led to great interest in the development of compact and economical accelerators. Laser wakefield accelerators can sustain accelerating gradients more than three orders of magnitude higher than those of radio-frequency accelerators7-10, and are regarded as an attractive option for driving compact X-ray free-electron lasers11. However, the realization of such devices remains a challenge owing to the relatively poor quality of electron beams that are based on a laser wakefield accelerator. Here we present an experimental demonstration of undulator radiation amplification in the exponential-gain regime by using electron beams based on a laser wakefield accelerator. The amplified undulator radiation, which is typically centred at 27 nanometres and has a maximum photon number of around 1010 per shot, yields a maximum radiation energy of about 150 nanojoules. In the third of three undulators in the device, the maximum gain of the radiation power is approximately 100-fold, confirming a successful operation in the exponential-gain regime. Our results constitute a proof-of-principle demonstration of free-electron lasing using a laser wakefield accelerator, and pave the way towards the development of compact X-ray free-electron lasers based on this technology with broad applications.

Critical Role of miR-130b-5p in Cardiomyocyte Proliferation and Cardiac Repair in Mice After Myocardial Infarction.

Poor proliferative capacity of adult cardiomyocytes is the primary cause of heart failure after myocardial infarction (MI), thus exploring the molecules and mechanisms that promote the proliferation of adult cardiomyocytes is crucially useful for cardiac repair after MI. Here, we found that miR-130b-5p was highly expressed in mouse embryonic and neonatal hearts and able to promote cardiomyocyte proliferation both in vitro and in vivo. Mechanistic studies revealed that miR-130b-5p mainly promoted the cardiomyocyte proliferation through the MAPK-ERK signaling pathway, and the dual-specific phosphatase 6 (Dusp6), a negative regulator of the MAPK-ERK signaling, was the direct target of miR-130b-5p. Moreover, we found that overexpression of miR-130b-5p could promote the proliferation of cardiomyocytes and improve cardiac function in mice after MI. These studies thus revealed the critical role of miR-130b-5p and its targeted MAPK-ERK signaling in the cardiomyocyte proliferation of adult hearts and proved that miR-130b-5p could be a potential target for cardiac repair after MI.

LncTarD 2.0: an updated comprehensive database for experimentally-supported functional lncRNA-target regulations in human diseases.

An updated LncTarD 2.0 database provides a comprehensive resource on key lncRNA-target regulations, their influenced functions and lncRNA-mediated regulatory mechanisms in human diseases. LncTarD 2.0 is freely available at (http://bio-bigdata.hrbmu.edu.cn/LncTarD or https://lnctard.bio-database.com/). LncTarD 2.0 was updated with several new features, including (i) an increased number of disease-associated lncRNA entries, where the current release provides 8360 key lncRNA-target regulations, with 419 disease subtypes and 1355 lncRNAs; (ii) predicted 3312 out of 8360 lncRNA-target regulations as potential diagnostic or therapeutic biomarkers in circulating tumor cells (CTCs); (iii) addition of 536 new, experimentally supported lncRNA-target regulations that modulate properties of cancer stem cells; (iv) addition of an experimentally supported clinical application section of 2894 lncRNA-target regulations for potential clinical application. Importantly, LncTarD 2.0 provides RNA-seq/microarray and single-cell web tools for customizable analysis and visualization of lncRNA-target regulations in diseases. RNA-seq/microarray web tool was used to mining lncRNA-target regulations in both disease tissue samples and CTCs blood samples. The single-cell web tools provide single-cell lncRNA-target annotation from the perspectives of pan-cancer analysis and cancer-specific analysis at the single-cell level. LncTarD 2.0 will be a useful resource and mining tool for the investigation of the functions and mechanisms of lncRNA deregulation in human disease.

Molecular and biological characterization of a bunyavirus infecting the brown planthopper (Nilaparvata lugens).

A negative-strand symbiotic RNA virus, tentatively named Nilaparvata lugens Bunyavirus (NLBV), was identified in the brown planthopper (BPH, Nilaparvata lugens). Phylogenetic analysis indicated that NLBV is a member of the genus Mobuvirus (family Phenuiviridae, order Bunyavirales). Analysis of virus-derived small interfering RNA suggested that antiviral immunity of BPH was successfully activated by NLBV infection. Tissue-specific investigation showed that NLBV was mainly accumulated in the fat-body of BPH adults. Moreover, NLBV was detected in eggs of viruliferous female BPHs, suggesting the possibility of vertical transmission of NLBV in BPH. Additionally, no significant differences were observed for the biological properties between NLBV-infected and NLBV-free BPHs. Finally, analysis of geographic distribution indicated that NLBV may be prevalent in Southeast Asia. This study provided a comprehensive characterization on the molecular and biological properties of a symbiotic virus in BPH, which will contribute to our understanding of the increasingly discovered RNA viruses in insects.

Pore-Matched Sponge for Microorganisms Pushes Electron Extraction Limit in Microbial Fuel Cells.

Microbial fuel cells (MFCs) are of great potential for wastewater remediation and chemical energy recovery. Nevertheless, limited by inefficient electron transfer between microorganisms and electrode, the remediation capacity and output power density of MFCs are still far away from the demand of practical application. Herein, a pore-matching strategy is reported to develop uniform electroactive biofilms by inoculating microorganisms inside a pore-matched sponge, which is assembled of core-shell polyaniline@carbon nanotube (PANI@CNT). The maximum power density achieved by the PANI@CNT bioanode is 7549.4 ± 27.6 mW m-2 , which is higher than the excellent MFCs with proton exchange membrane reported to date, while the coulombic efficiency also attains a considerable 91.7 ± 1.2%. The PANI@CNT sponge enriches the exoelectrogen Geobacter significantly, and is proved to play the role of conductive pili in direct electron transfer as it down-regulates the gene encoding pilA. This work exemplifies a practicable strategy to develop excellent bioanode to boost electron extraction in MFCs and provides in-depth insights into the enhancement mechanism.

Activation of CTU2 expression by LXR promotes the development of hepatocellular carcinoma.

Cytosolic thiouridylase 2 (CTU2) is an enzyme modifying transfer RNAs post-transcriptionally, which has been implicated in breast cancer and melanoma development. And we found CTU2 participated in hepatocellular carcinoma (HCC) progression here. HepG2 cells as well as xenograft nude mice model were employed to investigate the role of CTU2 in HCC development in vitro and in vivo respectively. Further, we defined CTU2 as a Liver X receptor (LXR) targeted gene, with a typical LXR element in the CTU2 promoter. CTU2 expression was activated by LXR agonist and depressed by LXR knockout. Interestingly, we also found CTU2 took part in lipogenesis by directly enhancing the synthesis of lipogenic proteins, which provided a novel mechanism for LXR regulating lipid synthesis. Meanwhile, lipogenesis was active during cell proliferation, particularly in tumor cells. Reduction of CTU2 expression was related to reduced tumor burden and synergized anti-tumor effect of LXR ligands by inducing tumor cell apoptosis and inhibiting cell proliferation. Taken together, our study identified CTU2 as an LXR target gene. Inhibition of CTU2 expression could enhance the anti-tumor effect of LXR ligand in HCC, identifying CTU2 as a promising target for HCC treatment and providing a novel strategy for the application of LXR agonists in anti-tumor effect.

Titanium dioxide nanoparticles alleviates polystyrene nanoplastics induced growth inhibition by modulating carbon and nitrogen metabolism via melatonin signaling in maize.

BACKGROUND: Nanoplastics, are emerging pollutants, present a potential hazard to food security and human health. Titanium dioxide nanoparticles (Nano-TiO2), serving as nano-fertilizer in agriculture, may be important in alleviating polystyrene nanoplastics (PSNPs) toxicity. RESULTS: Here, we performed transcriptomic, metabolomic and physiological analyzes to identify the role of Nano-TiO2 in regulating the metabolic processes in PSNPs-stressed maize seedlings (Zea mays L.). The growth inhibition by PSNPs stress was partially relieved by Nano-TiO2. Furthermore, when considering the outcomes obtained from RNA-seq, enzyme activity, and metabolite content analyses, it becomes evident that Nano-TiO2 significantly enhance carbon and nitrogen metabolism levels in plants. In comparison to plants that were not subjected to Nano-TiO2, plants exposed to Nano-TiO2 exhibited enhanced capabilities in maintaining higher rates of photosynthesis, sucrose synthesis, nitrogen assimilation, and protein synthesis under stressful conditions. Meanwhile, Nano-TiO2 alleviated the oxidative damage by modulating the antioxidant systems. Interestingly, we also found that Nano-TiO2 significantly enhanced the endogenous melatonin levels in maize seedlings. P-chlorophenylalanine (p-CPA, a melatonin synthesis inhibitor) declined Nano-TiO2-induced PSNPs tolerance. CONCLUSIONS: Taken together, our data show that melatonin is involved in Nano-TiO2-induced growth promotion in maize through the regulation of carbon and nitrogen metabolism.

The effect of corneal power on the accuracy of 14 IOL power formulas.

BACKGROUND: This study evaluates the impact of corneal power on the accuracy of 14 newer intraocular lens (IOL) calculation formulas in cataract surgery. The aim is to assess how these formulas perform across different corneal curvature ranges, thereby guiding more precise IOL selection. METHODS: In this retrospective case series, 336 eyes from 336 patients who underwent cataract surgery were studied. The cohort was divided into three groups according to preoperative corneal power. Key metrics analyzed included mean prediction error (PE), standard deviation of PE (SD), mean absolute prediction error (MAE), median absolute error (MedAE), and the percentage of eyes with PE within ± 0.25 D, 0.50 D, ± 0.75 D, ± 1.00 D and ± 2.00 D. RESULTS: In the flat K group (Km < 43 D), VRF-G, Emmetropia Verifying Optical Version 2.0 (EVO2.0), Kane, and Hoffer QST demonstrated lower SDs (± 0.373D, ± 0.379D, ± 0.380D, ± 0.418D, respectively) compared to the VRF formula (all P < 0.05). EVO2.0 and K6 showed significantly different SDs compared to Barrett Universal II (BUII) (all P < 0.02). In the medium K group (43 D ≤ Km < 46 D), VRF-G, BUII, Karmona, K6, EVO2.0, Kane, and Pearl-DGS recorded lower MAEs (0.307D to 0.320D) than Olsen (OLCR) and Castrop (all P < 0.03), with RBF3.0 having the second lowest MAE (0.309D), significantly lower than VRF and Olsen (OLCR) (all P < 0.05). In the steep K group (Km ≥ 46D), RBF3.0, K6, and Kane achieved significantly lower MAEs (0.279D, 0.290D, 0.291D, respectively) than Castrop (all P < 0.001). CONCLUSIONS: The study highlights the varying accuracy of newer IOL formulas based on corneal power. VRF-G, EVO2.0, Kane, K6, and Hoffer QST are highly accurate for flat corneas, while VRF-G, RBF3.0, BUII, Karmona, K6, EVO2.0, Kane, and Pearl-DGS are recommended for medium K corneas. In steep corneas, RBF3.0, K6, and Kane show superior performance.

Constructing vaccination slogans in the late stage of vaccine launch: an experimental study based on the framing effect theory.

BACKGROUND: Vaccination is an important strategy for overcoming public health crises. Considerable studies have analyzed strategies to promote people's willingness to vaccinate, but few have explored effective strategies based on the stage of vaccine launch. This study considered the framing effect theory to explore whether egoism, altruism and loss frames can boost vaccination willingness when people feel the vaccine is effective in the late stage of vaccine launch. METHODS: This study designed a scenario experiment consisting of three experimental groups (egoism, altruism and loss frames) and one control group (non-framed). Participants (N = 1085) from China were randomly assigned to any of the four groups. Vaccination willingness, perceived vaccine effectiveness and control variables included perceived susceptibility, perceived severity, worry about the side effects of vaccination and socio-demographics were collected. RESULTS: Perceived vaccine effectiveness and message frames can increase people's willingness to be vaccinated. Message frames can amplify the positive impact of perceived effectiveness on vaccination willingness. Moreover, loss-framed messages had a stronger amplification effect than egoistic- and altruistic-framed messages. CONCLUSIONS: Governments and other health authorities should prioritize the loss-framed approach when constructing vaccination slogans to maximize vaccination willingness when vaccines are considered effective at the late implementation stage of the vaccine strategy.

Alkaloids from Fritillaria przewalskii Bulbs and Their Anti-Alzheimer's Disease Activities.

Three undescribed isosteroidal alkaloids, przewalskines A-C (1-3), as well as seven known alkaloids (4-10) were obtained from Fritillaria przewalskii bulbs. Their structures were deduced by extensive HRESIMS, 1D NMR, and 2D NMR analyses, and their bioactivities were evaluated involving the anti-inflammatory and inhibitory potencies on AChE, BChE, and Aß aggregation. Compound 4 revealed the potent effect on inhibiting Aß aggregation activity with IC50 value of 33.1 µM, AChE activity with IC50 value of 6.9 µM, and also showed NO release inhibitory acitivity with IC50 value of 32.6 µM. These findings contribute new multi-.target anti-AD agents and embody the chemical diversity of F. przewalskii.

A regio-specific 4'-O-methyltransferase from Epimedium pseudowushanense regiospecifically catalyzing 8-prenylkeampferol to icaritin.

Epimedium is widely used in traditional Chinese medicine and contains rich bioactive compounds. These compounds often have a methyl group at their 4'-OH position catalyzed by methyltransferases. Therefore, studying methyltransferases in Epimedium plants is of great significance. In this study, a flavonol methyltransferase, EpOMT4, was isolated from Epimedium pseudowushanense B.L. Guo. The recombinant enzyme regiospecifically transferred a methyl group to the 4'-OH position of 8-prenylkaempferol forming icaritin. The study demonstrates that enzymatic methylation of flavonoids in Epimedium plants holds significant potential and could provide a promising alternative method for the biosynthetic production of bioactive methylated prenylflavonoids.

Characterization and Functional Analysis of the 17-Beta Hydroxysteroid Dehydrogenase 2 (hsd17b2) Gene during Sex Reversal in the Ricefield Eel (Monopterus albus).

In mammals, 17-beta hydroxysteroid dehydrogenase 2 (Hsd17b2) enzyme specifically catalyzes the oxidation of the C17 hydroxyl group and efficiently regulates the activities of estrogens and androgens to prevent diseases induced by hormone disorders. However, the functions of the hsd17b2 gene involved in animal sex differentiation are still largely unclear. The ricefield eel (Monopterus albus), a protogynous hermaphroditic fish with a small genome size (2n = 24), is usually used as an ideal model to study the mechanism of sex differentiation in vertebrates. Therefore, in this study, hsd17b2 gene cDNA was cloned and its mRNA expression profiles were determined in the ricefield eel. The cloned cDNA fragment of hsd17b2 was 1230 bp, including an open reading frame of 1107 bp, encoding 368 amino acid residues with conserved catalytic subunits. Moreover, real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) analysis showed that hsd17b2 mRNA expressed strongly in the ovaries at early developmental stages, weakly in liver and intestine, and barely in testis and other tissues. In particular, hsd17b2 mRNA expression was found to peak in ovaries of young fish and ovotestis at the early stage, and eventually declined in gonads from the late ovotestis to testis. Likewise, chemical in situ hybridization results indicated that the hsd17b2 mRNA signals were primarily detected in the cytoplasm of oogonia and oocytes at stage I-II, subsequently concentrated in the granulosa cells around the oocytes at stage Ⅲ-Ⅳ, but undetectable in mature oocytes and male germ cells. Intriguingly, in ricefield eel ovaries, hsd17b2 mRNA expression could be significantly reduced by 17ß-estradiol (E2) or tamoxifen (17ß-estradiol inhibitor, E2I) induction at a low concentration (10 ng/mL) and increased by E2I induction at a high concentration (100 ng/mL). On the other hand, both the melatonin (MT) and flutamide (androgen inhibitor, AI) induction could significantly decrease hsd17b2 mRNA expression in the ovary of ricefield eel. This study provides a clue for demonstrating the mechanism of sexual differentiation in fish. The findings of our study imply that the hsd17b2 gene could be a key regulator in sexual differentiation and modulate sex reversal in the ricefield eel and other hermaphroditic fishes.

Investigating the Hepatoprotective Properties of Mulberry Leaf Flavonoids against Oxidative Stress in HepG2 Cells.

Oxidative stress significantly contributes to ageing and disease, with antioxidants holding promise in mitigating its effects. Functional foods rich in flavonoids offer a potential strategy to mitigate oxidative damage by free radicals. We investigated the protective effects of mulberry leaf flavonoids (MLF) against H2O2-induced oxidative damage in HepG2 cells. It assessed the inhibitory effect of MLF (62.5-500 µg/mL) on H2O2-induced oxidative damage by analyzing cellular morphology and oxidative stress markers, including ROS production, mitochondrial membrane potential, antioxidant enzyme levels, MDA, and apoptosis-related proteins. The results demonstrated that MLF prevented spiny cell formation triggered by 750 µM H2O2 and significantly reduced ROS levels, restored mitochondrial membrane potential, decreased lactate dehydrogenase and alanine transaminase leakage, and reduced MDA content induced by H2O2. MLF also modulated antioxidant enzymes and attenuated oxidative damage to HepG2 cell DNA, as confirmed by staining techniques. These findings indicate the potential of MLF as a hepatoprotective agent against oxidative damage in HepG2 cells.

[Clinical characteristics and genetic analysis of a patient with Acephalic spermatozoa syndrome due to variant of PMFBP1 gene].

OBJECTIVE: To analyze the clinical characteristics and genetic basis of a male patient with primary infertility caused by Acephalic spermatozoa syndrome. METHODS: A patient who had presented at the Henan Provincial People's Hospital on October 1, 2022 was selected as the study subject. Clinical data and results of laboratory exams and sperm electron microscopy were collected. The patient was subjected to whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing and pathogenicity analysis. RESULTS: WES revealed that the patient has harbored compound heterozygous variants of the PMFBP1 gene, namely c.853del (p.Ala285Leufs*24) and c.1276A>T (p.Lys426X), which were both unreported previously. Sanger sequencing suggested that the c.853del (p.Ala285Leufs*24) variant has derived from his deceased mother, whilst the c.1276A>T (p.Lys426X) variant has derived from his father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were classified as pathogenic (PVS1+PM2_Supporting+PP4). CONCLUSION: The compound heterozygous variants of the PMFBP1 gene probably underlay the Acephalic spermatozoa syndrome in this patient. The discovery of the novel variants has also enriched the mutational spectrum of Acephalic spermatozoa syndrome.

Acceptor-Reactivity-Controlled Stereoconvergent Synthesis and Immunological Activity of a Unique Pentasaccharide from the Cell Wall Polysaccharide of Cutibacterium acnes C7.

Bacterial cell-surface polysaccharides are involved in various biological processes and have attracted widespread attention as potential targets for developing carbohydrate-based drugs. However, the accessibility to structurally well-defined polysaccharide or related active oligosaccharide domains remains challenging. Herein, we describe an efficiently stereocontrolled approach for the first total synthesis of a unique pentasaccharide repeating unit containing four difficult-to-construct 1,2-cis-glycosidic linkages from the cell wall polysaccharide of Cutibacterium acnes C7. The features of our approach include: 1) acceptor-reactivity-controlled glycosylation to stereoselectively construct two challenging rare 1,2-cis-ManA2,3(NAc)2 (ß-2,3-diacetamido-2,3-dideoxymannuronic acid) linkages, 2) combination use of 6-O-tert-butyldiphenylsilyl (6-O-TBDPS)-mediated steric shielding effect and ether solvent effect to stereoselectively install a 1,2-cis-glucosidic linkage, 3) bulky 4,6-di-O-tert-butylsilylene (DTBS)-directed glycosylation to stereospecifically construct a 1,2-cis-galactosidic linkage, 4) stereoconvergent [2+2+1] and one-pot chemoselective glycosylation to rapidly assemble the target pentasaccharide. Immunological activity tests suggest that the pentasaccharide can induce the production of proinflammatory cytokine TNF-α in a dose-dependent manner.

Characterization and Engineering of Two Highly Paralogous Sesquiterpene Synthases Reveal a Regioselective Reprotonation Switch.

Sesquiterpene synthases (STPSs) catalyze carbocation-driven cyclization reactions that can generate structurally diverse hydrocarbons. The deprotonation-reprotonation process is widely used in STPSs to promote structural diversity, largely attributable to the distinct regio/stereoselective reprotonations. However, the molecular basis for reprotonation regioselectivity remains largely understudied. Herein, we analyzed two highly paralogous STPSs, Artabotrys hexapetalus (-)-cyperene synthase (AhCS) and ishwarane synthase (AhIS), which catalyze reactions that are distinct from the regioselective protonation of germacrene A (GA), resulting in distinct skeletons of 5/5/6 tricyclic (-)-cyperene and 6/6/5/3 tetracyclic ishwarane, respectively. Isotopic labeling experiments demonstrated that these protonations occur at C3 and C6 of GA in AhCS and AhIS, respectively. The cryo-electron microscopy-derived AhCS complex structure provided the structural basis for identifying different key active site residues that may govern their functional disparity. The structure-guided mutagenesis of these residues resulted in successful functional interconversion between AhCS and AhIS, thus targeting the three active site residues [L311-S419-C458]/[M311-V419-A458] that may act as a C3/C6 reprotonation switch for GA. These findings facilitate the rational design or directed evolution of STPSs with structurally diverse skeletons.

A novel mutation in PCD-associated gene DNAAF3 causes male infertility due to asthenozoospermia.

Primary ciliary dyskinesia (PCD) is a rare autosomal-recessive disease manifested with recurrent infections of respiratory tract and infertility. DNAAF3 is identified as a novel gene associated with PCD and different mutations in DNAAF3 results in different clinical features of PCD patients, such as situs inversus, sinusitis and bronchiectasis. However, the sperm phenotypic characteristics of PCD males are generally poorly investigated. Our reproductive medicine centre received a case of PCD patient with infertility, who presented with sinusitis, recurrent infections of the lower airway and severe asthenozoospermia; However, no situs inversus was found in the patient. A novel homozygous mutation in DNAAF3(c.551T>A; p.V184E) was identified in the PCD patient by whole-exome sequencing. Subsequent Sanger sequencing further confirmed that the DNAAF3 had a homozygous missense variant in the fifth exon. Transmission electron microscopy and immunostaining analysis of the sperms from the patient showed a complete absence of outer dynein arms and partial absence of inner dynein arms, which resulted in the reduction in sperm motility. However, this infertility was overcome by intracytoplasmic sperm injections, as his wife achieved successful pregnancy. These findings showed that the PCD-associated pathogenic mutation within DNAAF3 also causes severe asthenozoospermia and male infertility ultimately due to sperm flagella axoneme defect in humans. Our study not only contributes to understand the sperm phenotypic characteristics of patients with DNAAF3 mutations but also expands the spectrum of DNAAF3 mutations and may contribute to the genetic diagnosis and therapy for infertile patient with PCD.

Inhibition of high-fat diet-induced obesity via reduction of ER-resident protein Nogo occurs through multiple mechanisms.

Obesity is a risk factor for insulin resistance, type 2 diabetes, and cardiovascular diseases. Reticulon-4 (Nogo) is an endoplasmic reticulum-resident protein with unclear functions in obesity. Herein, we investigated the effect of Nogo on obesity and associated metabolic disorders. Human serum samples were collected to explore the relationship between circulating Nogo-B and body mass index value. Nogo-deficient and WT littermate control mice were fed normal chow or high-fat diet (HFD) for 14 weeks, and HFD-induced obese C57BL/6J mice were injected scrambled or Nogo siRNA for 2 weeks. We found that in human and mouse serum, Nogo-B was positively correlated to body mass index/bodyweight and lipid profiles. Reduced Nogo (by genetic deletion or siRNA transfection) protected mice against HFD-induced obesity and related metabolic disorders. We demonstrate that Nogo deficiency reversed HFD-induced whitening of brown adipose tissue, thereby increasing thermogenesis. It also ameliorated lipid accumulation in tissues by activating the adiponectin-adiponectin receptor 1-AMP-activated kinase α signaling axis. Finally, Nogo deficiency potently reduced HFD-induced serum proinflammatory cytokines and infiltration of macrophages into metabolic organs, which is related to enhanced NF-κB p65 degradation via the lysosome pathway. Collectively, our study suggests that reduced levels of Nogo protect mice against HFD-induced obesity by increasing thermogenesis and energy metabolism while inhibiting NF-κB-mediated inflammation. Our results indicate that inhibition of Nogo may be a potential strategy for obesity treatment.

Efficient Aerobic Oxidative Coupling of Methyl Heteroarenes with Indoles.

Direct oxidative coupling of inert C(sp3 )-H bond has been a great challenge. Herein, an environmentally friendly aerobic oxidative coupling of α-methyl substituted N-heteroarenes with indoles is reported. A variety of diheteroaryl ketones were prepared in good yields (up to 72 %). This protocol features simple operation and broad substrates scope (26 examples). Significantly, a plausible mechanism about catalytic cycle was proposed, and two key intermediates were confirmed by high resolution mass spectrometry.

Comparing the efficacy and safety of different analgesic strategies after open hemorrhoidectomy: a systematic review and network meta-analysis.

PURPOSE: To evaluate the clinical efficacy and safety of different analgesic interventions in the treatment of pain after open hemorrhoidectomy by systematic review and network meta-analysis. METHODS: Randomized controlled trials that met the inclusion criteria in PubMed, Cochrane Library, Embase, Web of Science, Scopus, CNKI, WANFANG DATA, and VIP were searched from the date of database construction to June 28, 2022. RESULTS: Among the 13 randomized controlled trials (RCTs), 731 patients were included in the network meta-analysis. Most interventions are more effective than placebo in relieving postoperative pain. 24 h postoperative Visual Analogue Scale (VAS): glyceryl trinitrate (GTN) (mean difference (MD) - 4.20, 95% CI - 5.35, - 3.05), diltiazem (MD - 1.97, 95% CI - 2.44, - 1.51), botulinum toxin (BT) (MD - 1.50, 95% CI - 2.25, - 0.75), sucralfate (MD - 1.01, 95% CI - 1.53, - 0.49), and electroacupuncture (EA) (MD - 0.45, 95% CI - 0.87, - 0.04). 48 h postoperative VAS: diltiazem (MD - 2.45, 95% CI - 2.74, - 2.15), BT (MD - 2.18, 95% CI - 2.52, - 1.84), and sucralfate (MD - 1.41, 95% CI - 1.85, - 0.97). 7 d postoperative VAS: diltiazem (MD - 2.49, 95% CI - 3.20, - 1.78) and sucralfate (MD - 1.42, 95% CI - 2.00, - 0.85). The first postoperative defecation VAS: EA (MD - 0.70, 95% CI - 0.95, - 0.46). There are few data on intervention safety, and additional high-quality RCTs are expected to study this topic in the future. CONCLUSION: Diltiazem ointment may be the most effective medication for pain relief following open hemorrhoidectomy, and it can dramatically reduce pain within one week of surgery. The second and third recommended medications are BT and sucralfate ointment. GTN has a significant advantage in alleviating pain 24 h after open hemorrhoidectomy, but whether it causes headache is debatable; thus, it should be used with caution. EA's analgesic efficacy is still unknown. There was limited evidence on the safety of the intervention in this study, and it was simply presented statistically.