Rh(III)-Catalyzed C7-Alkylation of Isatogens with Malonic Acid Diazoesters.

Rh(III)-catalyzed C7-alkylation of isatogens (indolin-3-one N-oxides) with malonic acid diazoesters has been developed. This strategy utilizes oxygen anion on the N-oxide group of isatogens as a directing group and successfully achieves the synthesis of a series of C7-alkylated isatogens with moderate to good yields (48-86% yields). Moreover, the N-oxides of isatogens can not only serve as the simple directing group for C7-H bond cleavage but also be deoxidized for easy removal.

Clinical practice of sepsis-induced immunosuppression: Current immunotherapy and future options.

Sepsis is a potentially fatal condition characterized by the failure of one or more organs due to a disordered host response to infection. The development of sepsis is closely linked to immune dysfunction. As a result, immunotherapy has gained traction as a promising approach to sepsis treatment, as it holds the potential to reverse immunosuppression and restore immune balance, thereby improving the prognosis of septic patients. However, due to the highly heterogeneous nature of sepsis, it is crucial to carefully select the appropriate patient population for immunotherapy. This review summarizes the current and evolved treatments for sepsis-induced immunosuppression to enhance clinicians' understanding and practical application of immunotherapy in the management of sepsis.

Brucella Infection Regulates Thioredoxin-Interacting Protein Expression to Facilitate Intracellular Survival by Reducing the Production of Nitric Oxide and Reactive Oxygen Species.

Thioredoxin-interacting protein (TXNIP) is a multifunctional protein that functions in tumor suppression, oxidative stress, and inflammatory responses. However, how TXNIP functions during microbial infections is rarely reported. In this study, we demonstrate that Brucella infection decreased TXNIP expression to promote its intracellular growth in macrophages by decreasing the production of NO and reactive oxygen species (ROS). Following Brucella abortus infection, TXNIP knockout RAW264.7 cells produced significantly lower levels of NO and ROS, compared with wild-type RAW264.7 cells. Inducible NO synthase (iNOS) inhibitor treatment reduced NO levels, which resulted in a dose-dependent restoration of TXNIP expression, demonstrating that the expression of TXNIP is regulated by NO. In addition, the expression of iNOS and the production of NO were dependent on the type IV secretion system of Brucella Moreover, Brucella infection reduced TXNIP expression in bone marrow-derived macrophages and mouse lung and spleen. Knocked down of the TXNIP expression in bone marrow-derived macrophages increased intracellular survival of Brucella These findings revealed the following: 1) TXNIP is a novel molecule to promote Brucella intracellular survival by reducing the production of NO and ROS; 2) a negative feedback-regulation system of NO confers protection against iNOS-mediated antibacterial effects. The elucidation of this mechanism may reveal a novel host surveillance pathway for bacterial intracellular survival.

[Research Hotspots and Trends of Multimorbidity].

Objective To clarify the hotspots and trends of multimorbidity research and to provide evidence for further research in China. Methods Papers on multimorbidity were retrieved from PubMed and Web of Science (from inception to August 11,2021).BICOMB and gCLUTO were used for bibliometric and clustering analysis,and CiteSpace was employed for analysis of authors and citations,and burst detection of keywords. Results The research on multimorbidity has been on the rise.Among the authors,Mercer SW published the most papers on this topic and Fortin M was the most cited author.Karolinska Institute topped the institutions in the number of published papers,and the paper published in Lancet by Barnett K in 2012 was the most cited.A total of 75 high-frequency keywords were extracted,on the basis of which seven research hotspots were summarized:epidemiology (including the prevalence and trend),medication (involving polypharmacy,medication compliance,etc.),medical expenditure (including cost and medical services),aging (such as elderly patients,frailty,and disability),psychology (involving mental health,social support,etc.),multimorbidity management (such as the treatment,primary health care,and integrated care),and comorbidity of cardiovascular and metabolic diseases (involving obesity,stroke,diabetes,etc.). Conclusions Multimorbidity is concerned as a major health threat and public health problem worldwide.The management of multimorbidity is more complex than that of one disease,which thus faces more challenges.Therefore,researchers,health care providers,and policy-makers should underscore it.

Bacterial community in saline farmland soil on the Tibetan plateau: responding to salinization while resisting extreme environments.

BACKGROUND: Salinization damages the health of soil systems and reduces crop yields. Responses of microbial communities to salinized soils and their functional maintenance under high salt stress are valuable scientific problems. Meanwhile, the microbial community of the salinized soil in the plateau environment is less understood. Here, we applied metagenomics technology to reveal the structure and function of microorganisms in salinized soil of the Tibetan Plateau. RESULTS: The diversity of composition and function of microbial community in saline soil have changed significantly. The abundances of chemoautotrophic and acidophilic bacteria comprising Rhodanobacter, Acidobacterium, Candidatus Nitrosotalea, and Candidatus Koribacter were significantly higher in saline soil. The potential degradation of organic carbon in the saline soil, as well as the production of NO and N2O via denitrification, and the production of sulfate by sulfur oxidation were significantly higher than the non-saline soil. Both types of soils were rich in genes encoding resistance to environmental stresses (i.e., cold, ultraviolet light, and hypoxia in Tibetan Plateau). The resistance of the soil microbial communities to the saline environment is based on the absorption of K+ as the main mechanism, with cross-protection proteins and absorption buffer molecules as auxiliary mechanisms in our study area. Network analysis showed that functional group comprising chemoautotrophic and acidophilic bacteria had significant positive correlations with electrical conductivity and total sulfur, and significant negative correlations with the total organic carbon, pH, and available nitrogen. The soil moisture, pH, and electrical conductivity are likely to affect the bacterial carbon, nitrogen, and sulfur cycles. CONCLUSIONS: These results indicate that the specific environment of the Tibetan Plateau and salinization jointly shape the structure and function of the soil bacterial community, and that the bacterial communities respond to complex and harsh living conditions. In addition, environmental feedback probably exacerbates greenhouse gas emissions and accelerates the reduction in the soil pH. This study will provide insights into the microbial responses to soil salinization and the potential ecological risks in the special plateau environment.

Clinical Impacts and Outcomes With Possible Donor-Derived Infection in Infected Donor Liver Transplantation: A Single-Center Retrospective Study in China.

BACKGROUND: Information on possible donor-derived transmission events in China is limited. We evaluated the impacts of liver transplantation from infected deceased-donors, analyzed possible donor-derived bacterial or fungal infection events in recipients, and evaluated the etiologic agents' characteristics and cases outcomes. METHODS: A single-center observational study was performed from January 2015 to March 2017 to retrospectively collect data from deceased-donors diagnosed with infection. Clinical data were recorded for each culture-positive donor and the matched liver recipient. The microorganisms were isolated and identified, and antibiotic sensitivity testing was performed. The pathogens distribution and incidence of possible donor-derived infection (P-DDI) events were analyzed and evaluated. RESULTS: Information from 211 donors was collected. Of these, 82 donors were infected and classified as the donation after brain death category. Overall, 149 and 138 pathogens were isolated from 82 infected donors and 82 matched liver recipients, respectively. Gram-positive bacteria, Gram-negative bacteria, and fungi accounted for 42.3% (63 of 149), 46.3% (69 of 149), and 11.4% (17 of 149) of pathogens in infected donors. The incidence of multidrug-resistant bacteria was high and Acinetobacter baumannii was the most concerning species. Infections occurred within the first 2 weeks after liver transplantation with an organ from an infected donor. Compared with the noninfection recipient group, the infection recipient group experienced a longer mechanical ventilation time (P = .004) and intensive care unit stay (P = .003), a higher incidence of renal dysfunction (P = .026) and renal replacement therapy (P = .001), and higher hospital mortality (P = .015). Possible donor-derived infection was observed in 14.6% of cases. Recipients with acute-on-chronic liver failure were more prone to have P-DDI than recipients with other diseases (P = .007; odds ratio = 0.114; 95% confidence interval, .025-.529). CONCLUSIONS: When a liver recipient receives a graft from an infected deceased-donor, the postoperative incidence of infection is high and the infection interval is short. In addition, when a possible donor-derived, drug-resistant bacterial infection occurs, recipients may have serious complications and poor outcomes.

The Carboxyl Terminus of Tegument Protein pUL21 Contributes to Pseudorabies Virus Neuroinvasion.

Following its entry into cells, pseudorabies virus (PRV) utilizes microtubules to deliver its nucleocapsid to the nucleus. Previous studies have shown that PRV VP1/2 is an effector of dynein-mediated capsid transport. However, the mechanism of PRV for recruiting microtubule motor proteins for successful neuroinvasion and neurovirulence is not well understood. Here, we provide evidence that PRV pUL21 is an inner tegument protein. We tested its interaction with the cytoplasmic light chains using a bimolecular fluorescence complementation (BiFC) assay and observed that PRV pUL21 interacts with Roadblock-1. This interaction was confirmed by coimmunoprecipitation (co-IP) assays. We also determined the efficiency of retrograde and anterograde axonal transport of PRV strains in explanted neurons using a microfluidic chamber system and investigated pUL21's contribution to PRV neuroinvasion in vivo Further data showed that the carboxyl terminus of pUL21 is essential for its interaction with Roadblock-1, and this domain contributes to PRV retrograde axonal transport in vitro and in vivo Our findings suggest that the carboxyl terminus of pUL21 contributes to PRV neuroinvasion.IMPORTANCE Herpesviruses are a group of DNA viruses that infect both humans and animals. Alphaherpesviruses are distinguished by their ability to establish latent infection in peripheral neurons. After entering neurons, the herpesvirus capsid interacts with cellular motor proteins and undergoes retrograde transport on axon microtubules. This elaborate process is vital to the herpesvirus lifecycle, but the underlying mechanism remains poorly understood. Here, we determined that pUL21 is an inner tegument protein of pseudorabies virus (PRV) and that it interacts with the cytoplasmic dynein light chain Roadblock-1. We also observed that pUL21 promotes retrograde transport of PRV in neuronal cells. Furthermore, our findings confirm that pUL21 contributes to PRV neuroinvasion in vivo Importantly, the carboxyl terminus of pUL21 is responsible for interaction with Roadblock-1, and this domain contributes to PRV neuroinvasion. This study offers fresh insights into alphaherpesvirus neuroinvasion and the interaction between virus and host during PRV infection.

Terlipressin relieves intestinal and renal injuries induced by acute mesenteric ischemia via PI3K/Akt pathway.

Background: To date, the effect of vasopressin on organ damages after acute mesenteric ischemia (MI) remains poorly understood. Aims: To investigate the effect of terlipressin, a selective vasopressin V1 receptor agonist, versus norepinephrine on the intestinal and renal injuries after acute MI, and to explore the underlying mechanism of terlipressin. Methods: Acute MI model was produced by clamping the superior mesenteric artery for 1 hour. Immediately after unclamping, terlipressin or norepinephrine was intravenously administered for 2 hours. Meanwhile, in vitro, RAW264.7 cells were treated with lipopolysaccharide or lipopolysaccharide+terlipressin. In addition, wortmannin was used to determine the role of phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt) pathway in the potential impacts of terlipressin. Results: MI led to severe hypotension, caused notable intestinal and renal impairments and resulted in high mortality, which were markedly improved by terlipressin or norepinephrine. Terlipressin increased mean arterial pressure, decreased intestinal epithelial cell apoptosis, inhibited the generation of M1 macrophage in intestinal and renal tissues, and hindered the release of inflammatory cytokines after MI. Moreover, in cultured macrophages, terlipressin reduced the mRNA level of specific M1 markers and the release of inflammatory cytokines caused by lipopolysaccharide challenge. Wortmannin decreased the expression of PI3K and Akt induced by terlipressin in cells and in tissues, and abolished the above protective effects conferred by terlipressin. Conclusions: Terlipressin or norepinephrine could effectively improve organ damages and mortality after acute MI. Terlipressin elevates blood pressure and inhibits intestinal epithelial apoptosis and macrophage M1 polarization via the PI3K/Akt pathway.

Brucella infection regulates peroxiredoxin-5 protein expression to facilitate intracellular survival by reducing the production of nitric oxide and reactive oxygen species.

Peroxiredoxin-5 (Prdx5) is a multifunctional protein involved in oxidative stress, apoptosis and inflammatory responses. However, how Prdx5 functions during microbial infections is rarely reported. In this study, we demonstrate that Brucella infection increased Prdx5 expression to promote its intracellular growth in macrophages. Further study show that B. abortus infection promoted its intracellular growth by decreasing the production of nitric oxide and reactive oxygen species. In addition, the expression of Prdx5 was independent on live Brucella and the type IV secretion system of Brucella. Instead, its expression was regulated by the lipopolysaccharide of Brucella. Moreover, Brucella infection increased Prdx5 expression in primary macrophage and mice. Collectively, these findings demonstrate for the first time that Prdx5 promotes Brucella intracellular growth by decreasing the production of NO and ROS. This finding provides new insights into the evasive strategies of Brucella and will be useful for the development of novel effective therapeutic approaches to treat Brucella infections.

Expression of pseudorabies virus-encoded long noncoding RNAs in epithelial cells and neurons.

Long noncoding RNAs (lncRNAs) play important roles in regulating eukaryotic genome replication and gene expression in diverse biological systems. Here, we identified lncRNAs transcribed from pseudorabies virus (PRV)-infected PK-15 cells. Based on high-throughput sequencing data, we obtained 87,263,926 and 93,947,628 clean reads from mock-infected and PRV-infected PK-15 cells, respectively. Through a normalized analytic protocol, we identified three novel viral lncRNAs. According to an analysis of differential expression between the mock-infected and PRV-infected cells, 4151 host lncRNAs were significantly upregulated and 2327 host lncRNAs were significantly downregulated in the latter group. Viral lncRNAs and several host lncRNAs were verified by northern blotting and real-time PCR. The findings showed that the viral lncRNA LDI might regulate the expression of IE180, a potent transcriptional activator of viral genes. Furthermore, we characterized the expression of viral lncRNAs in a culture of infected primary chicken dorsal root ganglia (DRG). Collectively, the obtained data suggest that PRV generates lncRNAs in both epithelial cells and chick DRG neurons.

Critical Care Resources in Guangdong Province of China: Three Surveys from 2005 to 2015.

OBJECTIVES: Data about the critical care resources in China remain scarce. The purpose of this study was to investigate the variation and distribution of critical care resources in Guangdong province from 2005 to 2015. DESIGN: Data in regard to critical care resources were collected through questionnaires and visits every 5 years from 2005. SETTING: All hospitals in Guangdong province were screened and hospitals that provide critical care services were enrolled. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: One hundred eleven, 158, and 284 hospitals that provide critical care services were enrolled in the three consecutive surveys respectively. The number of ICUs, ICU beds, intensivists, and nurses increased to 324, 3,956, 2,470, and 7,695, respectively, by 2015. Adjusted by population, the number of ICU beds per 100,000 (100,000) population increased by 147.7% from 2005 to 2015, and the number of intensivists and nurses per 100,000 population increased by 35.3% and 55.1% from 2011 to 2015. However, the numbers in the Pearl River Delta, a richer area, were higher than those in the non-Pearl River Delta area (ICU beds: 4.64 vs 2.58; intensivists: 2.90 vs 1.61; nurses: 9.30 vs 4.71 in 2015). In terms of staff training, only 17.85% of intensivists and 14.29% of nurses have completed a formal accredited critical care training program by 2015. CONCLUSIONS: Our study was the first one to investigate the trend and distribution of critical care resources in China. The quantity of ICU beds and staff has been increasing rapidly, but professional training for staff was inadequate. The distribution of critical care resources was unbalanced. Our study can be beneficial for healthcare policymaking and the allocation of critical care resources in Guangdong province and other provinces in China.

Active Ankle Movements Prevent Formation of Lower-Extremity Deep Venous Thrombosis After Orthopedic Surgery.

BACKGROUND The aim of this study was to assess the preventive value of active ankle movements in the formation of lower-extremity deep venous thrombosis (DVT), attempting to develop a new method for rehabilitation nursing after orthopedic surgery. MATERIAL AND METHODS We randomly assigned 193 patients undergoing orthopedic surgery in the lower limbs into a case group (n=96) and a control group (n=97). The control group received routine nursing while the case group performed active ankle movements in addition to receiving routine nursing. Maximum venous outflow (MVO), maximum venous capacity (MVC), and blood rheology were measured and the incidence of DVT was recorded. RESULTS On the 11th and 14th days of the experiment, the case group had significantly higher MVO and MVC than the control group (all P<0.05). The whole-blood viscosity at high shear rate and the plasma viscosity were significantly lower in the case group than in the control group on the 14th day (both P<0.05). During the experiment, a significantly higher overall DVT incidence was recorded in the control group (8 with asymptomatic DVT) compared with the case group (1 with asymptomatic DVT) (P=0.034). During follow-up, the case group presented a significantly lower DVT incidence (1 with symptomatic DVT and 4 with asymptomatic DVT) than in the control group (5 with symptomatic DVT and 10 with asymptomatic DVT) (P=0.031). CONCLUSIONS Through increasing MVO and MVC and reducing blood rheology, active ankle movements may prevent the formation of lower-extremity DVT after orthopedic surgery.

Inverted tetrahedron-pyramidal micropatterned polymer films for boosting light output power in flip-chip light-emitting diodes.

We report the improved light output power in gallium nitride-based green flip-chip light-emitting diodes (FCLEDs) employed with inverted tetrahedron-pyramidal micropatterned polydimethylsiloxane (ITPM PDMS) films as an encapsulation and protection layer. The micropatterns are transferred into the surface of PDMS films from the sapphire substrate master molds with two-dimensional periodic hexagonal TPM arrays by a soft imprint lithography method. The ITPM PDMS film laminated on the sapphire dramatically enhances the diffuse transmittance (T(D)) in a wavelength (λ) range of 400-650 nm, exhibiting the larger T(D) value of ~53% at λ = 525 nm, (cf., T(D) ~1% for planar sapphire). By introducing the ITPM PDMS film on the outer surface of sapphire in FCLEDs, the light output power is enhanced, indicating the increment percentage of ~11.1% at 500 mA of injection current compared to the reference FCLED without the ITPM PDMS film, together with better electroluminescence intensity and far-field radiation pattern.

Broadband high-reflective distributed Bragg reflectors based on amorphous silicon films for semiconductor laser facet coatings.

We fabricated amorphous silicon (a-Si)-based distributed Bragg reflectors (DBRs) consisting of alternating dense/porous films (i.e., pair) for a center wavelength (λ(c)) of 0.96 µm by oblique angle deposition (OAD) technique using an electron-beam evaporation system. The dense (high refractive index, i.e., high-n) and porous (low-n) a-Si films were deposited at two incident vapor flux angles of 0° and 80° in the OAD, respectively. Their optical reflectance characteristics were investigated in the wavelength range of 0.6-1.5 µm, including theoretical comparison using a rigorous coupled-wave analysis method. Above three pairs, the reflectivity (R) of a-Si DBRs was almost saturated at wavelengths around 0.96 µm, exhibiting R values of >97%. For the a-Si DBR with only three pairs, a broad normalized stop bandwidth (Δλ/λ(c)) of ∼22.5% was obtained at wavelengths of ∼0.87-1.085 µm, keeping high R values of >95%. To simply demonstrate the feasibility of device applications, the a-Si DBR with three pairs was coated as a high-reflection layer at the rear facet of GaAs/InGaAs quantum-well laser diodes (LDs) operating at λ=0.96 µm. For the LDs coated with three-pair a-Si DBR, external differential quantum efficiency (η(d)) was nearly doubled compared to the uncoated LDs, indicating the η(d) value of ∼50.6% (i.e., η(d)∼25.5% for the uncoated LDs).

Tunable distributed Bragg reflectors with wide-angle and broadband high-reflectivity using nanoporous/dense titanium dioxide film stacks for visible wavelength applications.

Highly-tolerant distributed Bragg reflectors (DBRs) based on the same materials consisting of nanoporous/dense titanium dioxide (TiO2) film pair structures with wide-angle and broadband highly-reflective properties at visible wavelengths are reported. For a high refractive index contrast, the two dense and nanoporous TiO2 film stacks are alternatingly deposited on silicon (Si) substrates by a oblique angle deposition (OAD) method at two vapor flux angles (θα) of 0 and 80° for high and low refractive indices, respectively. For the TiO2 DBRs at a center wavelength (λ(c)) of 540 nm, the maximum level in reflectance (R) band is increased with increasing the number of pairs, exhibiting high R values of > 90% for 5 pairs, and the normalized stop bandwidth (∆λ/λ(c)) of ~17.8% is obtained. At λ(c) = 540 nm, the patterned TiO2 DBR with 5 pairs shows an uniform relative reflectivity over a whole surface of 3 inch-sized Si wafer and a large-scalable fabrication capability with any features. The angle-dependent reflectance characteristics of TiO2 DBR at λ(c) = 540 nm are also studied at incident angles (θ(inc)) of 20-70° for p-, s-, and non-polarized lights in the wavelength region of 350-750 nm, yielding high R values of > 70.4% at θ(inc) values of 20-70° for non-polarized light. By adjusting the λ(c)/4 thicknesses of nanoporous and dense films, for λ(c) = 450, 540, and 680 nm, tunable broadband TiO2 DBRs with high R values of > 90% at wavelengths of 400-800 nm are realized.

A general strategy for all-solid-state batteries with agglomeration-free and high conductivity achieved by improving the interface compatibility of fillers and polymer matrix.

Composite solid electrolytes (CSEs) composed of polymer matrix and inorganic fillers show considerable potential for applications in all-solid-state lithium (Li) metal batteries. However, challenges such as fillers agglomeration and low lithium ion transference number (tLi+) remain significant obstacles to the practical application of CSEs. Herein, a general strategy of graft polymerization on the fillers surface to modulate the interface compatibility with the polymer matrix is proposed, and CSEs are prepared to verify the feasibility. The microstructure and composition of the surface coating of the fillers are analyzed, with subsequent studies of the fillers distribution within the CSEs confirming the improved interface compatibility. The enhancement of interface compatibility facilitates uniform dispersion of fillers, thereby greatly improving the utilization of fillers. CSEs exhibits high ionic conductivity (0.163 mS·cm-1 at 30 °C) and tLi+ (0.77), which gives the battery excellent rate performance and cycle stability. Therefore, chemical grafting of polymer onto the fillers surface to enhance the interface compatibility with the polymer matrix represents a promising strategy for the practical application of solid-state batteries.

Enhancing the Efficiency and Stability of Inverted Formamidinium-Cesium Lead-Triiodide Perovskite Solar Cells through Lewis Base Pretreatment of Buried Interfaces.

Mixed components of formamidinium(FA) and cesium (Cs)-based perovskite solar cells are the most hopeful for commercialization owing to their excellent operational and phase stabilities, especially for devices with inverted structure. The nonradiative recombination of carriers can be effectively suppressed through interface optimization, therefore, the performance of devices can be improved. Notably, the buried interface emerges as critical aspects such as charge transport, charge recombination kinetics, and morphology of perovskite films. This study focuses on a straightforward yet effective approach to overcome buried interface challenges between organic polymers (poly(-triarylamine) (PTAA) and FACs-based perovskite films. The PTAA substrate is pretreated with a Lewis base known as 2-butynoic acid (BA) with a C═O functional group. First, it can be an interfacial buffering layer, harmonizing stress mismatch between the perovskite and PTAA layers, consequently optimizing crystallization and improving perovskite film quality. Second, Pb2+ defect can be passivated at the buried interface of the perovskite film through binding with the C═O group of the BA molecule. This dual-function strategy leads to a substantial enhancement in both photoelectric conversion efficiency (PCE) and stability of devices. Finally, the PCE of the device-modified buried interface with BA reaches an impressive 23.33%. Furthermore, unencapsulated devices with BA treatment maintain approximately 94% of their initial efficiency after aging at maximum power point tracking for 1000 h.

Structure-Guided Design, Synthesis, and Antivirulence Assessment of Covalent Staphylococcus aureus Sortase A Inhibitors.

Sortase A (SrtA) is a membrane-associated cysteine transpeptidase required for bacterial virulence regulation and anchors surface proteins to cell wall, thereby assisting biofilm formation. SrtA is targeted in antivirulence treatments against Gram-positive bacterial infections. However, the development of potent small-molecule SrtA inhibitors is constrained owing to the limited understanding of the mode of action of inhibitors in the SrtA binding pocket. Herein, we designed and synthesized a novel class of covalent SrtA inhibitors based on the binding mode detailed in the X-ray crystal structure of the ML346/Streptococcus pyogenes SrtA complex. ML346 analog Y40 exhibited 2-fold increased inhibitory activity on Staphylococcus aureus SrtA and showed superior inhibitory effects on biofilm formation in vitro. Y40 protected Galleria mellonella larvae fromS. aureusinfections in vivo while minimally attenuating staphylococcal growth in vitro. Our study indicates that the covalent SrtA inhibitor Y40 is an antivirulence agent that is effective againstS. aureusinfections.

Intrasegmental recombination as an evolutionary force of Lassa fever virus.

Lassa fever (LF), caused by Lassa virus (LASV), is one of the most dangerous diseases to public health. Homologous recombination (HR) is a basic genetic power driving biological evolution. However, as a negative-stranded RNA virus, it is unknown whether HR occurs between LASVs and its influence on the outbreak of LF. In this study, after analyzing 575 S and 433 L segments of LASV collected in Africa, we found that LASV can achieve HR in both of its segments. Interestingly, although the length of S segment is less than half of the L segment, the proportion of LASVs with S recombinants is significantly higher than that with L recombinants. These results suggest that HR may be a feature of LASV, which can be set by natural selection to produce beneficial or eliminate harmful mutations for the virus, so it plays a role in LASV evolution during the outbreak of LF.