Low-sugar universal mRNA vaccine against coronavirus variants with deletion of glycosites in the S2 or stem of SARS-CoV-2 spike messenger RNA (mRNA).

Since the outbreak of Severe Acute Respiratory Syndrome Virus-2 (SARS-CoV-2) in 2019, more than 15 million spike protein sequences have been identified, raising a new challenge for the development of a broadly protective vaccine against the various emerging variants. We found that the virus, like most other human viruses, depends on host-made glycans to shield the conserved epitopes on spike protein from immune response and demonstrated that deletion of the glycan shields exposed highly conserved epitopes and elicited broadly protective immune responses. In this study, we identified 17 conserved epitopes from 14 million spike protein sequences and 11 of the conserved epitopes are in the S2 domain, including the six most conserved epitopes in the stem region. We also demonstrated that deletion of the glycosites in the spike messenger RNA (mRNA) S2 domain or the stem region exposed the highly conserved epitopes and elicited broadly protective immune responses, particularly CD-8+ T cell response against various SARS-CoV-2 variants, and other human coronaviruses including MERS, SARS viruses, and those causing common cold.

Safety and efficacy of radiotherapy combined with chemotherapy for recurrent metastatic renal pelvic and ureteral carcinoma.

PURPOSE: To retrospectively investigate the safety and efficacy of radiotherapy combined with chemotherapy for recurrent metastatic renal pelvic and ureteral carcinoma. METHODS: 109 patients were enrolled in this study, including 44 patients in the radiochemotherapy group and 65 patients in the chemotherapy group. Propensity score matching (PSM) was used to balance the baseline characteristics of the two groups by 1:1 matching. Kaplan-Meier method was used to calculate PFS and OS. Cox regression model was used for multivariate analysis. The side effects were evaluated by CTCAE v5.0 RESULTS: The median follow-up time was 14.5 months. Multivariate analysis showed that radiotherapy was a good independent prognostic factor for OS (HR: 0.327, 95% CI 0.157-0.680, P = 0.003). After matching, there were 40 patients in both groups, and the median PFS and OS in the radiochemotherapy group were longer than those in the chemotherapy group (PFS: 10.4 vs. 6.7 months, P = 0.035; OS: 43.5 vs. 18.8 months, P < 0.001). In addition, in the radiochemotherapy group, patients treated with radiotherapy before first-line chemotherapy failure had a longer PFS than those treated with radiotherapy after chemotherapy failure (median PFS: 15.7 vs. 6 months, P = 0.003). There was no significant difference in the incidence of grade 3-4 toxicities between the two groups (52.3% vs. 50.8%, P = 0.878). CONCLUSION: For patients with recurrent metastatic renal pelvic and ureteral carcinoma, radiotherapy combined with chemotherapy is well tolerable and expected to bring long-term survival benefits, and the benefits of early interventional radiotherapy may be more obvious.

Three stilbenes from pigeon pea with promising anti-methicillin-resistant Staphylococcus aureus biofilm formation activity.

Cajaninstilbene acid (CSA), longistylin A (LLA), and longistylin C (LLC) are three characteristic stilbenes isolated from pigeon pea. The objective of this study was to evaluate the antibacterial activity of these stilbenes against Staphylococcus aureus and even methicillin-resistant Staphylococcus aureus (MRSA) and test the possibility of inhibiting biofilm formation. The minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of these stilbenes were evaluated. And the results showed that LLA was most effective against tested strains with MIC and MBC values of 1.56 µg/mL followed by LLC with MIC and MBC values of 3.12 µg/mL and 6.25 µg/mL as well as CSA with MIC and MBC values of 6.25 µg/mL and 6.25-12.5 µg/mL. Through growth curve and cytotoxicity analysis, the concentrations of these stilbenes were determined to be set at their respective 1/4 MIC in the follow-up research. In an anti-biofilm formation assay, these stilbenes were found to be effectively inhibited bacterial proliferation, biofilm formation, and key gene expressions related to the adhesion and virulence of MRSA. It is the first time that the anti-S. aureus and MRSA activities of the three stilbenes have been systematically reported. Conclusively, these findings provide insight into the anti-MRSA mechanism of stilbenes from pigeon pea, indicating these compounds may be used as antimicrobial agents or additives for food with health functions, and contribute to the development as well as application of pigeon pea in food science.

Euryachincoside, a Novel Phenolic Glycoside with Anti-Hepatic Fibrosis Activity from Eurya chinensis.

Eurya chinensis has been recorded as a folk medicine traditionally used for treatment of a variety of symptoms. However, the phytochemical and pharmacological investigations of this plant are still scarce. A novel phenolic glycoside named Euryachincoside (ECS) was isolated by chromatographic separation from E. chinensis, and its chemical structure was identified by analysis of HRMS and NMR data. Its anti-hepatic fibrosis effects were evaluated in both HSC-T6 (rat hepatic stellate cells) and carbon tetrachloride (CCl4)-induced mice with Silybin (SLB) as the positive control. In an in vitro study, ECS showed little cytotoxicity and inhibited transforming growth factor-beta (TGF-ß)-induced Collagen I (Col1) along with alpha-smooth muscle actin (α-SMA) expressions in HSC-T6. An in vivo study suggested ECS significantly ameliorated hepatic injury, secretions of inflammatory cytokines, and collagen depositions. Moreover, ECS markedly mediated Smad2/3, nuclear factor kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways both in vitro and vivo. These present findings confirmed that ECS is a novel phenolic glycoside from E. chinensis with promising curative effects on hepatic fibrosis, and its mechanisms may include decreasing extracellular matrix accumulation, reducing inflammation and attenuating free radicals via Smad2/3, NF-κB and Nrf2 signaling pathways, which may shed light on the exploration of more effective phenolic glycoside-based anti-fibrotic agents.

Two new withanolides from the whole plants of Physalis peruviana.

Two new withaphysalin-type withanolides (18-O-ethylwithaphysalin R and 5-O-ethylphysaminimin C, 1 and 2), along with twelve known withanolides (3-14), were purified and identified from Physalis peruviana L. The chemical structures of these new isolates were elucidated through analyzing spectroscopic and HRESIMS data. All the obtained metabolites were appraised for their potential antiproliferative activity against the human breast cancer cell line MCF-7. Compound 7 was discovered to exhibit potent activity with an IC50 value of 3.51 µM and compounds 2, 6 and 14 showed weak cytotoxic effect.

Synthesis of Single-Layer Two-Dimensional Metal-Organic Frameworks M3 (HAT)2 (M=Ni, Fe, Co, HAT=1,4,5,8,9,12-hexaazatriphenylene) Using an On-Surface Reaction.

1,4,5,8,9,12-Hexaazatriphenylene (HAT) is one of the smallest polyheterocyclic aromatic building blocks for forming conjugated metal-organic frameworks (cMOFs). However, the strong inter-molecular steric hindrance impedes the growth of HAT-based cMOFs. Here we employ on-surface synthesis to grow single-layer two-dimensional cMOFs of M3 (HAT)2 (M=Ni, Fe, Co). Using scanning tunnelling microscopy and density-functional theory (DFT) analysis, we resolve that the frameworks comprise a hexagonal lattice of HAT molecules and a Kagome lattice of metal atoms. The DFT analysis indicates that Ni, Co and Fe carry a magnetic moment of 1.1, 2.5, and 3.7 µB, respectively. We anticipate that the small π-conjugated core of HAT and strong bidentate chelating coordination give rise to appealing electronic and magnetic properties.

Development of a nomogram predicting metastatic disease and the assessment of NCCN, AUA and EAU guideline recommendations for bone imaging in prostate cancer patients.

PURPOSE: We identified the risk predictors related to prostate cancer (PCa) metastasis using contemporary data in a community setting. Then, we assessed the performance of indications for bone imaging recommended from the NCCN, AUA and EAU guidelines. METHODS: Using the Surveillance, Epidemiology, and End Results database (2010-2015), we collected clinicopathological information from PCa patients. The associated risk factors found by multivariate analyses were used to establish forest plots and nomograms for distant metastasis (DM) and bone(s)-only metastasis (BM). We next evaluated the NCCN, AUA and EAU guidelines indications for the discovery of certain subgroups of patients who should receive bone imaging. RESULTS: A total of 120,136 patients were eligible for analysis, of which 96.7% had no metastasis. The odds ratios of positive DM and BM results were 13.90 times and 15.87 times higher in patients with a histologic grade group (GG) 5 than in the reference group. The concordance index of the nomograms based on race, age, T/N stage, PSA, GG, percentage of positive scores for predicting DM and BM was 0.942 and 0.928, respectively. Performance of the NCCN, AUA and EAU guidelines was high and relatively similar in terms of sensitivity (93.2-96.9%) and negative predictive value (99.8-99.9%). NCCN guidelines had the highest accuracy, specificity and positive likelihood ratio, while negative likelihood ratio was lowest in AUA guideline. CONCLUSION: Histologic GG 5 was the foremost factor for DM and BM. NCCN-based recommendations may be more rational in clinical practice. Nomograms predicting metastasis demonstrate high accuracy.

Self-wrinkling polyelectrolyte multilayers: construction, smoothing and the underlying mechanism.

Introducing wrinkling or rough features into substrates is of great practical significance to construct various functional surfaces. Due to the sensitivity of assembled units towards environmental stimuli, the internals of layer-by-layer films can be readily adjusted to generate various micro- and nanostructures. We previously described a self-roughening polyelectrolyte multilayer (PEM) to facilitate the introduction of surface microstructures. In the present work, the growth process of PEI/PAA multilayer films was investigated and the mean size of the surface microstructures was found to increase linearly with the film thickness. The spontaneous formation of these surface features can be attributed to swelling-induced film deformation during the assembling process, which is similar to the surface wrinkling of hydrogels undergoing a volume phase transition. When exposed to saturated humidity, the internal stress as well as the surface microstructures can be diminished spontaneously, leading to a flat surface over the substrates. Given the effect of the underlying film thickness on the characteristic wavelength of the surface wrinkles, multiscale surface microstructures can be readily realized by means of spatially presetting the distribution of the film thickness.

Feasibility of cetuximab and chemoradiotherapy combination in Chinese patients with unresectable stage III non-small cell lung cancer: a preliminary report.

OBJECTIVE: In recent years, the combination of cetuximab and chemoradiotherapy (CRT) has been used to treat stage III non-small cell lung cancer (NSCLC); however, limited data are available for Chinese patients. Herein, we report preliminary data from a phase I/II study testing the combination of cetuximab with inductive chemotherapy, followed by concurrent CRT (CCRT) in Chinese patients with stage III NSCLC. METHODS: Eligibility criteria were Zubrod performance status (PS) 0-1, forced expiratory volume in 1 second (FEV1) ≥1.2 L and adequate organ function. Enrolled patients received weekly cetuximab (initial dose of 400 mg/m(2) on day 1 of week 1 and a maintenance dose of 250 mg/m(2) on week 2 to the end of CCRT) with cisplatin/vinorelbine (NP) chemotherapy (every 3 weeks for 2 cycles from week 2, followed by two cycles of concomitant NP chemotherapy and intensity-modulated thoracic radiotherapy (TRT) (60-66 Gy/2 Gy). The primary endpoints were toxicity and feasibility. All patients received positron emission tomography-computerized tomography (PET-CT) scans within the 2 weeks prior to enrollment. Univariate analyses were used to assess the correlation between SUV-T, SUV-N, SUV-TOTAL, gender, age, histology, tumor-node-metastasis (TNM) stage, PS and smoking status and survival. Survival curves were generated for different populations using the Kaplan-Meier method and compared using a log-rank test. RESULTS: Seventeen patients were enrolled and 16 completed the full regime. The overall response rate (ORR) was 58.8% and 82.3% after the induction and CCRT phases, respectively. With a median follow-up duration of 27.6 months, the median survival was 27.6 months [95% confidence interval (CI): 11.3-43.9 months] with 1- and 2-year survival rates of 88.2% (95% CI, 60.6-96.9%) and 58.8% (95% CI, 60.6-77.8%), respectively. Three patients remain progression-free to date, and the median progression-free survival (PFS) was 13.5 months (95% CI, 6.8-20.2 months). No treatment-related death occurred; however, 76% of the patients experienced grade 3+ adverse events (AEs), including nausea/vomiting, intestinal obstruction, and esophagitis (<6%), while other AEs were mostly of hematological nature (71%). The cut-off values for SUV-T and SUV-TOTAL were 11 and 20, respectively. Univariate analyses revealed SUV-TOTAL (P=0.027), SUV-T (P=0.025), and PS (P=0.006) as potential survival predictors, with a hazard ratio (HR) of 3.4, 3.7, and 9.9, respectively. CONCLUSIONS: The combination of cetuximab with induction chemotherapy followed by CCRT appears feasible and promising. Local and locoregional maximal SUVs, defined by (18)F-FDG PET-CT scanning, may represent a prognostic indicator for long-term survival for these patients, which warrants further study.

Dose-Intensified Postoperative Radiation Therapy for Prostate Cancer: Long-Term Results From the PKUFH Randomized Phase 3 Trial.

PURPOSE: In the randomized, single-center, PKUFH phase 3 trial, dose-intensified (72 Gy) radiation therapy was compared with conventional (66 Gy) radiation therapy. In a previous study, we found no significant difference in biochemical progression-free survival (bPFS) between the 2 cohorts at 4 years. In the current analysis, we provide 7-year outcomes. METHODS AND MATERIALS: Patients with stage pT3-4, positive surgical margins, or a prostate-specific antigen increase ≥0.2 ng/mL after radical prostatectomy were randomly assigned 1:1 to receive either 72 Gy in 36 fractions or 66 Gy in 33 fractions. All the patients underwent image guided intensity modulated radiation therapy. The primary endpoint was bPFS. Secondary endpoints were distant metastasis-free survival (DMFS), cancer-specific survival (CSS), and overall survival (OS) as estimated using the Kaplan-Meier method. RESULTS: Between September 2011 and November 2016, 144 patients were enrolled with 73 and 71 in the 72- and 66-Gy cohorts, respectively. At a median follow-up of 89.5 months (range, 73-97 months), there was no difference in 7-year bPFS between the 72- and 66-Gy cohorts (70.3% vs 61.2%; hazard ratio [HR], 0.73; 95% CI, 0.41-1.29; P = .274). However, in patients with a higher Gleason score (8-10), the 72-Gy cohort had statistically significant improvement in 7-year bPFS compared with the 66-Gy cohort (66.5% vs 30.2%; HR, 0.37; 95% CI, 0.17-0.82; P = .012). In addition, in patients with multiple positive surgical margins, the 72-Gy cohort had statistically significant improvement in 7-year bPFS compared with single positive surgical margin (82.5% vs 57.5%; HR, 0.36; 95% CI, 0.13-0.99; P = .037). The 7-year DMFS (88.4% vs 84.9%; HR, 0.93; 95% CI, 0.39-2.23; P = .867), CSS (94.1% vs 95.5%; HR, 1.19; 95% CI, 0.42-3.39; P = .745), and OS (92.8% vs 94.1%; HR, 1.29; 95% CI, 0.51-3.24; P = .594) had no statistical differences between the 72- and 66-Gy cohorts. CONCLUSIONS: The current 7-year bPFS results confirmed our previous findings that dose escalation (72 Gy) demonstrated no improvement in 7-year bPFS, DMFS, CSS, or OS compared with the 66-Gy regimen. However, patients with a higher Gleason score (8-10) or multiple positive surgical margins might benefit from the 72-Gy regimen, but this requires further prospective research.

ATP6V0A1-dependent cholesterol absorption in colorectal cancer cells triggers immunosuppressive signaling to inactivate memory CD8+ T cells.

Obesity shapes anti-tumor immunity through lipid metabolism; however, the mechanisms underlying how colorectal cancer (CRC) cells utilize lipids to suppress anti-tumor immunity remain unclear. Here, we show that tumor cell-intrinsic ATP6V0A1 drives exogenous cholesterol-induced immunosuppression in CRC. ATP6V0A1 facilitates cholesterol absorption in CRC cells through RAB guanine nucleotide exchange factor 1 (RABGEF1)-dependent endosome maturation, leading to cholesterol accumulation within the endoplasmic reticulum and elevated production of 24-hydroxycholesterol (24-OHC). ATP6V0A1-induced 24-OHC upregulates TGF-ß1 by activating the liver X receptor (LXR) signaling. Subsequently, the release of TGF-ß1 into the tumor microenvironment by CRC cells activates the SMAD3 pathway in memory CD8+ T cells, ultimately suppressing their anti-tumor activities. Moreover, we identify daclatasvir, a clinically used anti-hepatitis C virus (HCV) drug, as an ATP6V0A1 inhibitor that can effectively enhance the memory CD8+ T cell activity and suppress tumor growth in CRC. These findings shed light on the potential for ATP6V0A1-targeted immunotherapy in CRC.

[Identification of origins of marker chromosomes using fluorescence in situ hybridization].

OBJECTIVE: To assess the value of fluorescence in situ hybridization (FISH) and bacterial artificial chromosome FISH (BAC-FISH) for the diagnosis for patients with marker chromosomes. METHODS: Sixteen patients with marker chromosomes were analyzed with technologies including GTG-banding, Q-banding, multiplex FISH and BAC-FISH. RESULTS: The marker chromosomes in the 16 patients were verified as der(Y) (2 cases), psu dic(Y) (1 case), psu dic(15) (1 case), dic(15) (1 case), del(Y) (1 case), r(X) (5 cases), i(14 or 22) (2 cases), i(18) (1 case). CONCLUSION: FISH and BAC-FISH can both verify the origin of marker chromosomes and provide accurate information for the diagnosis and treatment of patients.

Biomarkers for Prostate Cancer: From Diagnosis to Treatment.

Prostate cancer (PCa) is a widespread malignancy with global significance, which substantially affects cancer-related mortality. Its spectrum varies widely, from slow-progressing cases to aggressive or even lethal forms. Effective patient stratification into risk groups is crucial to therapeutic decisions and clinical trials. This review examines a wide range of diagnostic and prognostic biomarkers, several of which are integrated into clinical guidelines, such as the PHI, the 4K score, PCA3, Decipher, and Prolaris. It also explores the emergence of novel biomarkers supported by robust preclinical evidence, including urinary miRNAs and isoprostanes. Genetic alterations frequently identified in PCa, including BRCA1/BRCA2, ETS gene fusions, and AR changes, are also discussed, offering insights into risk assessment and precision treatment strategies. By evaluating the latest developments and applications of PCa biomarkers, this review contributes to an enhanced understanding of their role in disease management.

Transcriptome profiling Revealed the potential mechanisms of Shen Lin Bai Zhu San n-butanol extract on DSS induced Colitis in Mice and LC-MS analysis.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disorder in gastrointestinal tract. Shen Ling Bai Zhu San (SLBZS), which has a long history of use in Traditional Chinese Medicine (TCM), has been widely used to treat gastrointestinal diseases. The isolated fractions of TCM have also been proved to possess an important potential for treating diseases, which are due to their effective components. PURPOSE: In this study, we examined the possibility that SLBZS and its isolated active fractions may prevent DSS-induced colitis, and investigated the potential mechanisms by regulating genetic profile of colon. METHODS: Colitis mice were induced by 2.5% DSS for 7 days, and then SLBZS and different SLBZS extracts were administrated to protect the mice for 7 days. Body weight, diarrhea, bleeding in stool, colon length, spleen weight, cytokines of serum and colon and pathology of colon were assessed. The level of Ginsenoside Rg1, Re and Rb1 in different SLBZS extracts and qualitative analysis of n-butanol extract of SLBZS (S-Nb) was performed by HPLC and LC-MS, respectively. And the effects of S-Nb on the transcriptome in colitis were investigated. RESULTS: Our results showed that SLBZS and S-Nb significantly regained body weight, reduced DAI, splenomegaly and the length of colon and attenuated histological damage of the colon. Meanwhile, SLBZS and S-Nb markedly reduced the levels of TNF-α, IL-1ß and IL-6 and increased the level of IL-10 in serum and colon. These effects may be associated with the high levels of Ginsenoside Rg1, Re and Rb1 and rich variety of compounds in S-Nb including 6 ginsenosides, glycyrrhizin, L-tryptophan, and so on. Transcriptome analysis revealed that S-Nb selectively regulated 103 differentially expressed genes (DEGs), 36 of which were changed in DSS-induced mice. And the genes of Per2, Per3, Npy and Serpina3m were closely related to colitis and also restored by S-Nb with different extent. Remarkably, these DEGs modulated the biological functions of colitis mice, including extracellular region, response to external stimulus, MAPK signaling pathway and arginine and proline metabolism. CONCLUSIONS: These data indicated that SLBZS and S-Nb blunted DSS-induced colitis by modulating differentially expression gene profile and biological functions based on their ginsenosides and rich compounds.

Four new eudesmane-type and one new eremophilane-type sesquiterpenes from the whole plant of Carpesium abrotanoides L.

The extract of the whole plant of Carpesium abrotanoides L. yielded five new sesquiterpenes including four eudesmanes (1-4) and one eremophilane (5). The new compounds were characterized by spectroscopic analysis especially 1D and 2D NMR spectroscopy and HRESIMS data. Structurally, both compounds 1 and 2 were sesquiterpene epoxides and 2 owned an epoxy group at C-4/C-15 position to form a spiro skeleton. Compounds 4 and 5 were two sesquiterpenes without lactones and 5 possessed a carboxy group in the molecule. Additionally, all the isolated compounds were preliminarily evaluated for the inhibitory activity against SARS-CoV-2 main protease. As a result, compound 2 showed moderate activity with an IC50 value of 18.79 µM, while other compounds were devoid of noticeable activity (IC50 > 50 µM).

Uncovering the Secrets of Prostate Cancer's Radiotherapy Resistance: Advances in Mechanism Research.

Prostate cancer (PCa) is a critical global public health issue with its incidence on the rise. Radiation therapy holds a primary role in PCa treatment; however, radiation resistance has become increasingly challenging as we uncover more about PCa's pathogenesis. Our review aims to investigate the multifaceted mechanisms underlying radiation therapy resistance in PCa. Specifically, we will examine how various factors, such as cell cycle regulation, DNA damage repair, hypoxic conditions, oxidative stress, testosterone levels, epithelial-mesenchymal transition, and tumor stem cells, contribute to radiation therapy resistance. By exploring these mechanisms, we hope to offer new insights and directions towards overcoming the challenges of radiation therapy resistance in PCa. This can also provide a theoretical basis for the clinical application of novel ultra-high-dose-rate (FLASH) radiotherapy in the era of PCa.

A p-orbital honeycomb-Kagome lattice realized in a two-dimensional metal-organic framework.

The experimental realization of p-orbital systems is desirable because p-orbital lattices have been proposed theoretically to host strongly correlated electrons that exhibit exotic quantum phases. Here, we synthesize a two-dimensional Fe-coordinated bimolecular metal-organic framework which constitutes a honeycomb lattice of 1,4,5,8,9,12-hexaazatriphenylene molecules and a Kagome lattice of 5,15-di(4-pyridyl)-10,20-diphenylporphyrin molecules on a Au(111) substrate. Density-functional theory calculations show that the framework features multiple well-separated spin-polarized Kagome bands, namely Dirac cone bands and Chern flat bands, near the Fermi level. Using tight-binding modelling, we reveal that these bands are originated from two effects: the low-lying molecular orbitals that exhibit p-orbital characteristics and the honeycomb-Kagome lattice. This study demonstrates that p-orbital Kagome bands can be realized in metal-organic frameworks by using molecules with molecular orbitals of p-orbital like symmetry.

[Effects of electroacupuncture on gait and proliferation and differentiation of muscle satellite cell in rats with acute blunt trauma of gastrocnemius muscle].

OBJECTIVE: To observe the effects of electroacupuncture on threshold of pain, gait, proliferation and differentiation of muscle satellite cell in rats with acute blunt trauma of gastrocnemius muscle, and to explore the possible mechanism of electroacupuncture in promoting the repair of acute injury of skeletal muscle. METHODS: A total of 48 SD rats were randomly divided into a blank group (6 rats), a model group (24 rats) and an electroacupuncture group (18 rats). In the model group and the electroacupuncture group, the model of acute blunt trauma of gastrocnemius muscle was established by self-made impactor. In the electroacupuncture group, electroacupuncture was applied at "Chengshan" (BL 57) and "Yanglingquan" (GB 34) on the right side, with disperse-dense wave, in frequency of 2 Hz/100 Hz, once a day, 30 min each time. Electroacupuncture intervention was performed for 3, 7 and 14 days according to the sampling time. On the 1st, 3rd, 7th and 14th days after modeling, the mechanical withdrawal pain threshold of hindfoot was detected by Von Frey method; the standing time and the maximum contact area of the right hindfoot were recorded by Cat Walk XTTM animal gait analysis instrument; the morphology of the right gastrocnemius muscle and the number of inflammatory cells were observed by HE staining; the positive expression of paired box gene 7 (Pax7) and myogenic differentiation (MyoD) of the right gastrocnemius muscle was detected by immunofluorescence. RESULTS: After modeling, the muscle fiber rupture and massive infiltration of red blood cells and inflammatory cells were observed in the right gastrocnemius muscle; after electroacupuncture intervention, the morphology of muscle fiber was intact and the infiltration of inflammatory cells was improved. Compared with the blank group, in the model group, the differences of mechanical withdrawal pain threshold between the left and right foot were increased (P<0.05), the standing time was shortened and the maximum contact area of the right hindfoot was decreased (P<0.05), the number of inflammatory cells and the positive expression of Pax7 and MyoD of the right gastrocnemius muscle were increased (P<0.05) on the 1st, 3rd, 7th and 14th days after modeling. Compared with the model group, in the electroacupuncture group, the differences of mechanical withdrawal pain threshold were decreased (P<0.05), the standing time was prolonged (P<0.05), the number of inflammatory cells of right gastrocnemius muscle was decreased (P<0.05) on the 7th and 14th days after modeling; the maximum contact area of the right hindfoot was increased (P<0.05), the positive expression of MyoD of the right gastrocnemius muscle was increased (P<0.05) on the 3rd, 7th and 14th days after modeling; the positive expression of Pax7 of the right gastrocnemius muscle was increased (P<0.05) on the 3rd day after modeling. CONCLUSION: Electroacupuncture can effectively improve the pain threshold and gait in rats with acute blunt trauma of gastrocnemius muscle, and promote the repair of skeletal muscle injury, the mechanism may be related to the up-regulation of Pax7 and MyoD, so as to promoting the proliferation and differentiation of muscle satellite cell.

Four new stilbenes and one new flavonoid with potential antibacterial and anti-SARS-CoV-2 activity from Cajanus cajan.

Four new stilbenes (1-4) and one new flavonoid (5), named cajanines D-H, together with three known stilbenes (6-8) were isolated from the leaves of Cajanus cajan (L.) Millsp. (pigeon pea). The structures of these compounds were elucidated unambiguously on the basis of IR, 1D, and 2D NMR, as well as HRESIMS data. Structurally, stilbenes 1-4 bore an isopentyl side chain, and further hydroxylation of compounds 1-3 generated a greater variety of structural forms. Compound 5 was a flavonoid owning an isopentyl side chain. Besides, antibacterial activity of the isolated compounds against Staphylococcus aureus, Bacillus cereus, and Escherichia coli was studied in vitro. Compounds 1-8 were endowed with profound antibacterial activity. Among them, the MIC values of compounds 4, 6, and 7 against S. aureus were 1.56, 0.78, and 0.78 µg/mL, respectively, among which 6 and 7 had better antibacterial activity than the positive control Vancomycin with the MIC values of 1.56 µg/mL. Additionally, the anti-SARS-CoV-2 main protease activity of all the isolated compounds was evaluated, and it was worth mentioning that the IC50 values of compounds 5-7 were 8.27, 4.65, and 8.30 µM, respectively, being comparable to the positive control Ebselen. Our findings may provide valuable guidance for the application of stilbenes as lead compounds in the future for the development of drugs with antibacterial or anti-COVID-19 activity.

The sesquiterpenes with the COVID-19 Mpro inhibitory activity from the Carpesium abrotanoides L.

The extract of the whole plant of Carpesium abrotanoides L. yielded four new sesquiterpenes including a novel skeleton (claroguaiane A, 1), two guaianolides (claroguaianes B-C, 2-3), and one eudesmanolide (claroeudesmane A, 4), together with three known sesquiterpenoids (5-7). The structures of the new compounds were elucidated by spectroscopic analysis especially 1D and 2D NMR spectroscopy and HRESIMS data. Additionally, all the isolated compounds were preliminarily evaluated for the inhibitive activity of COVID-19 Mpro. As a result, compound 5 showed moderate activity with an IC50 value of 36.81 µM and compound 6 exhibited a potent inhibitory effect with an IC50 value of 16.58 µM, while other compounds were devoid of noticeable activity (IC50 > 50 µM).