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The emerging SARS-CoV-2 variants, commonly with many mutations in S1 subunit of spike (S) protein are weakening the efficacy of the current vaccines and antibody therapeutics. This calls for the variant-proof SARS-CoV-2 vaccines targeting the more conserved regions in S protein. Here, we designed a recombinant subunit vaccine, HR121, targeting the conserved HR1 domain in S2 subunit of S protein. HR121 consisting of HR1–linker1–HR2–linker2–HR1, is conformationally and functionally analogous to the HR1 domain present in the fusion intermediate conformation of S2 subunit. Immunization with HR121 in rabbits and rhesus macaques elicited highly potent cross-neutralizing antibodies against SARS-CoV-2 and its variants, particularly Omicron sublineages. Vaccination with HR121 achieved near-full protections against prototype SARS-CoV-2 infection in hACE2 transgenic mice, Syrian golden hamsters and rhesus macaques, and effective protection against Omicron BA.2 infection in Syrian golden hamsters. This study demonstrates that HR121 is a promising candidate of variant-proof SARS-CoV-2 vaccine with a novel conserved target in the S2 subunit for application against current and future SARS-CoV-2 variants.

Background Sugarcane is the most important sugar crop, contributing > 80% of global sugar production. High sucrose content is a key target of sugarcane breeding, yet sucrose improvement in sugarcane remains extremely slow for decades. Molecular breeding has the potential to break through the genetic bottleneck of sucrose improvement. Dissecting the molecular mechanism(s) and identifying the key genetic elements controlling sucrose accumulation will accelerate sucrose improvement by molecular breeding. In our previous work, a proteomics dataset based on 12 independent samples from high- and low-sugar genotypes treated with ethephon or water was established. However, in that study, employing conventional analysis, only 25 proteins involved in sugar metabolism were identified . Results In this work, the proteomics dataset used in our previous study was reanalyzed by three different statistical approaches, which include a logistic marginal regression, a penalized multiple logistic regression named Elastic net, as well as a Bayesian multiple logistic regression method named Stochastic search variable selection (SSVS) to identify more sugar metabolism-associated proteins. A total of 507 differentially abundant proteins (DAPs) were identified from this dataset, with 5 of them were validated by western blot. Among the DAPs, 49 proteins were found to participate in sugar metabolism-related processes including photosynthesis, carbon fixation as well as carbon, amino sugar, nucleotide sugar, starch and sucrose metabolism. Based on our studies, a putative network of key proteins regulating sucrose accumulation in sugarcane is proposed, with glucose-6-phosphate isomerase, 2-phospho-D-glycerate hydrolyase, malate dehydrogenase and phospho-glycerate kinase, as hub proteins. Conclusions The sugar metabolism-related proteins identified in this work are potential candidates for sucrose improvement by molecular breeding. Further, this work provides an alternative solution for omics data processing.

Infections of clinical methicillin-resistant Staphylococcus aureus (MRSA) is a very tough public health problem and a challenge of new drug development. Nearly 90 Diels-Alder adducts (DAAs) have so far been isolated from Morus plants, but only a few of them have been evaluated for their anti-MRSA activities. To study the antibacterial compounds of DAAs from the root barks’ section of Morus alba L. and their synergism with antibacterial agents against clinical MRSA strains, bioassay-guided phytochemical methods were used to screen the active components. Minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) were assayed through broth serial microdilution. The synergism were evaluated by checker board microdilution and dynamic time-kill experiments. Three DAAs (multicaulisin (1), sanggenon G (2) and albanin G (3)) were isolated and identified from M. alba root barks. They were determined with potent effect against MRSA isolates with MICs/MBCs at 2–8/16–128 mg/L. They also showed synergy with conventional antibacterial agents, especially the aminoglycosides, with fractional inhibitory concentration indices (FICIs) ranged from 0.19 to 0.50 and the dose reduction indices (DRIs) ranged from 16 to 2. The MRSA resistance to the antibiotics could be reversed by compounds 1–3. The dose-dependent bactericidal synergism against MRSA was observed as well. The study released for the first time the anti-MRSA synergism of DAAs from M. alba root barks with antibacterial agents and the reversal of MRSA resistance to aminoglycosides. The results may be valuable for further development of new antibacterial drugs and synergists against MRSA infections.

Background Understanding the prevalence and evolution of HIV-1 drug resistance (DR) and associated mutation patterns is critical to implementing free antiretroviral therapy in Yunnan, the first antiretroviral treatment location in China. Here We provide a basis for understanding the occurrence and development of HIV-1 resistance in Yunnan and a theoretical foundational for strategy to delay HIV-1 drug resistance and achieve successful individualized treatment. Methods Plasma samples from different cities/prefectures were collected at Yunnan Provincial Hospital of Infectious Disease from January 2010 to September 2016, and those from drug-resistant individuals were genotyped using in-house assays, 88 patients were selected for the study who had been on treatment for ≥6 months (and for whom drug resistance was then measured), and each patient had at least 3 genotype resistance tests and who were enrolled to analyze mutation and evolution of HIV resistance. Results 264 Pol sequences of 88 patients were obtained. Drug resistance levels to eight drugs increased to varying degrees with prolonged treatment. Resistance to efavirenz (EFV) and etravirine (ETR) showed the highest change, comparisons of resistant changes to second and first and to third and second agents showed altered level of drug resistance were 25 and 20 cases, 28 and 18 cases, respectively. The smallest change was Lopinavir/Ritonavir (LPV/r) present 2 and 3 cases; Resistance to lamivudine (3TC) and lopinavir/ritonavir (LPV/r) was high among patients detected thrice, whereas other drugs were distributed in all resistance levels. M184 V/I (26.14%), T69S (11.36%), and T215Y/I (10.23%) mutations were the most common in nucleoside reverse transcriptase inhibitors (NRTIs), and K103 N/R/S (21.59%), V179D/E (20.45%) in Non-NRTIs (NNRTIs). Furthermore, L10 V/F/I (6.82%), A71V (4.55%), and I54V (4.55%) mutations were common in protease inhibitors (PIs). Conclusions We found dynamic genotypic changes in HIV-1 drug-resistance in Yunnan, with prolonged treatment, and drug resistance was inevitable. However, resistance to different drugs occurred at varying times, and mutation site emergence was the main cause. These findings enhance our understanding of evolution and regulation, and are valuable for developing HIV-1 DR prevention strategies in Yunnan.

The coal-bearing strata of the deep Upper Paleozoic in the GS Sag have high hydrocarbon potential. Because of the absence of seismic data, we use electromagnetic (MT) and gravity data jointly to delineate the distribution of deep targets based on well logging and geological data. First, a preliminary geological model is established by using three-dimensional (3D) MT inversion results. Second, using the formation density and gravity anomalies, the preliminary geological model is modified by interactive inversion of the gravity data. Then, we conduct MT-constrained inversion based on the modified model to obtain an optimal geological model until the deviations at all stations are minimized. Finally, the geological model and a seismic profile in the middle of the sag is analysed. We determine that the deep reflections of the seismic profile correspond to the Upper Paleozoic that reaches thickness up to 800 m. The processing of field data suggests that the joint MT–gravity modeling and constrained inversion can reduce the multiple solutions for single geophysical data and thus improve the recognition of deep formations. The MT-constrained inversion is consistent with the geological features in the seismic section. This suggests that the joint MT and gravity modeling and constrained inversion can be used to delineate deep targets in similar basins.

Objective To observe the impact of electroacupuncture on the pain threshold and the content of excitatory amino acids in the spinal cord of the rats with neuropathic pain to discuss the mechanism of electroacupuncture in treating neuropathic pain.

Trace amounts of benzene hydrocarbons obtained in Jiaozhou Bay (Qingdao) were enriched by sorption on a GDX-102 column and eluted by carbon disulfide. The eluate was concentrated and then determined by capillary column gas chromatography.

Sample seawater containing trace methyl mercury was acidified and adsorbed on hydrosulfo-cotton, washed with hydrochloric acid, extracted by benzene and dried, and then determined by a gas chromatograph with electron capture detector. This method, which can detect a minimum concentration of 0.1×10−10%, can be used to monitor the 10−10% content of methyl mercury in seawater.