Vaccine elicitation and structural basis for antibody protection against alphaviruses.

Alphaviruses are RNA viruses that represent emerging public health threats. To identify protective antibodies, we immunized macaques with a mixture of western, eastern, and Venezuelan equine encephalitis virus-like particles (VLPs), a regimen that protects against aerosol challenge with all three viruses. Single- and triple-virus-specific antibodies were isolated, and we identified 21 unique binding groups. Cryo-EM structures revealed that broad VLP binding inversely correlated with sequence and conformational variability. One triple-specific antibody, SKT05, bound proximal to the fusion peptide and neutralized all three Env-pseudotyped encephalitic alphaviruses by using different symmetry elements for recognition across VLPs. Neutralization in other assays (e.g., chimeric Sindbis virus) yielded variable results. SKT05 bound backbone atoms of sequence-diverse residues, enabling broad recognition despite sequence variability; accordingly, SKT05 protected mice against Venezuelan equine encephalitis virus, chikungunya virus, and Ross River virus challenges. Thus, a single vaccine-elicited antibody can protect in vivo against a broad range of alphaviruses.

NRF1-mediated mitochondrial biogenesis antagonizes innate antiviral immunity.

Mitochondrial biogenesis is the process of generating new mitochondria to maintain cellular homeostasis. Here, we report that viruses exploit mitochondrial biogenesis to antagonize innate antiviral immunity. We found that nuclear respiratory factor-1 (NRF1), a vital transcriptional factor involved in nuclear-mitochondrial interactions, is essential for RNA (VSV) or DNA (HSV-1) virus-induced mitochondrial biogenesis. NRF1 deficiency resulted in enhanced innate immunity, a diminished viral load, and morbidity in mice. Mechanistically, the inhibition of NRF1-mediated mitochondrial biogenesis aggravated virus-induced mitochondrial damage, promoted the release of mitochondrial DNA (mtDNA), increased the production of mitochondrial reactive oxygen species (mtROS), and activated the innate immune response. Notably, virus-activated kinase TBK1 phosphorylated NRF1 at Ser318 and thereby triggered the inactivation of the NRF1-TFAM axis during HSV-1 infection. A knock-in (KI) strategy that mimicked TBK1-NRF1 signaling revealed that interrupting the TBK1-NRF1 connection ablated mtDNA release and thereby attenuated the HSV-1-induced innate antiviral response. Our study reveals a previously unidentified antiviral mechanism that utilizes a NRF1-mediated negative feedback loop to modulate mitochondrial biogenesis and antagonize innate immune response.

A vaccine targeting the RBD of the S protein of SARS-CoV-2 induces protective immunity.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a respiratory disease called coronavirus disease 2019 (COVID-19), the spread of which has led to a pandemic. An effective preventive vaccine against this virus is urgently needed. As an essential step during infection, SARS-CoV-2 uses the receptor-binding domain (RBD) of the spike protein to engage with the receptor angiotensin-converting enzyme 2 (ACE2) on host cells1,2. Here we show that a recombinant vaccine that comprises residues 319-545 of the RBD of the spike protein induces a potent functional antibody response in immunized mice, rabbits and non-human primates (Macaca mulatta) as early as 7 or 14 days after the injection of a single vaccine dose. The sera from the immunized animals blocked the binding of the RBD to ACE2, which is expressed on the cell surface, and neutralized infection with a SARS-CoV-2 pseudovirus and live SARS-CoV-2 in vitro. Notably, vaccination also provided protection in non-human primates to an in vivo challenge with SARS-CoV-2. We found increased levels of RBD-specific antibodies in the sera of patients with COVID-19. We show that several immune pathways and CD4 T lymphocytes are involved in the induction of the vaccine antibody response. Our findings highlight the importance of the RBD domain in the design of SARS-CoV-2 vaccines and provide a rationale for the development of a protective vaccine through the induction of antibodies against the RBD domain.

Single-cell transcriptomic analysis reveals a decrease in the frequency of macrophage-RGS1high subsets in patients with osteoarticular tuberculosis.

BACKGROUND: Cell subsets differentially modulate host immune responses to Mycobacterium tuberculosis (MTB) infection. However, the nature and functions of these subsets against osteoarticular tuberculosis (OTB) are unclear. Here, we aimed to understand the phenotypes and functions of immune cell subsets in patients with OTB using single-cell RNA sequencing (scRNA-Seq). METHODS: Pathological and healthy adjacent tissues were isolated from patients with OTB and subjected to scRNA-Seq. Unsupervised clustering of cells was performed based on gene expression profiles, and uniform manifold approximation and projection was used for clustering visualization. RESULTS: Thirteen cell subsets were identified in OTB tissues. scRNA-seq datasets of patients and healthy controls (HCs) showed that infection changed the frequency of immune cell subsets in OTB tissues. Myeloid cell examination revealed nine subsets. The frequency of macrophage-RGS1high subsets decreased in OTB tissues; this increased MTB susceptibility in an SLC7A11/ferroptosis-dependent manner. Immunohistochemistry assays and flow cytometry for patients with OTB and osteoarticular bacterial infection (OBI) and HCs verified that the frequency of macrophage-RGS1high subset decreased in OTB tissues and blood samples, thereby distinguishing patients with OTB from HCs and patients with OBI. CONCLUSION: The macrophage-RGS1high subset levels were decreased in patients with OTB, and would be up-regulated after effective treatment. Therefore, the clinical significance of this study is to discover that macrophage-RGS1high subset may serve as a potential biomarker for OTB diagnosis and treatment efficacy monitoring.

Nonlinear-mirror mode-locked crystal waveguide laser by intracavity fourth-harmonic loss modulation: publisher's note.

This publisher's note contains a correction to Opt. Lett.48, 6064 (2024)10.1364/OL.509275.

Optimized terahertz generation in BNA organic crystals with chirped Ti:sapphire laser pulses.

We report on the efficient generation of intense terahertz radiation from the organic crystal N-benzyl-2-methyl-4-nitroaniline pumped by chirped Ti:sapphire femtosecond laser pulses. The THz energy and spectrum as a function of the pump fluence and duration of the chirped laser pulses are studied systematically. For the appropriate positively chirped pump pulses, a significant boost in the THz generation efficiency by a factor of around 2.5 is achieved, and the enhancement of high-frequency components (>1 THz) shortens the THz pulse duration. Via complete characterization of THz properties and transmitted laser spectra, this nonlinear behavior is attributed to the extended effective interaction length for phase matching as a result of the self-phase modulation of the intense pump laser pulses. Numerical calculations well reproduce the experimental observation. Our results demonstrate a robust, efficient, strong-field (up to several MV/cm) THz source using the common sub-10 mJ and sub-100 fs Ti:sapphire laser systems without optical parametric amplifiers.

Investigating Xiaochaihu Decoction's fever-relieving mechanism via network pharmacology, molecular docking, dynamics simulation, and experiments.

Xiaochaihu Decoction（XCHD）is a classic prescription for the treatment of fever, but the mechanism is not clear. In this study, We elucidated the mechanism of action through network pharmacology and molecular docking. A rat fever model was established to verify the prediction results of network pharmacology. The analysis revealed that 120 intersection targets existed between XCHD and fever. The TP53, STAT3, RELA, MAPK1, AKT1, TNF and MAPK14 as potential core targets of XCHD in fever treatment. GO and KEGG pathway enrichment analyses indicated that XCHD may act through pathways such as the AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, IL-17 signaling pathway. Molecular docking results demonstrated that quercetin, kaempferol, ß-sitosterol, stigmasterol and baicalein exhibited strong binding activity to key targets. Animal experiments showed that XCHD significantly reduced body temperature and levels of IL-1ß, IL-6, TNF-α, NO, PGE2, and cAMP in rats with fever. Importantly, no significant difference was observed between the XCHD self-emulsifying nano phase plus suspension phase and XCHD group. XCHD exerts its therapeutic effects on fever through a multi-ingredient, multi-target, and multi-pathway approach.

Light-induced ligand-to-metal charge transfer of Fe(III)-OR species in organic synthesis.

Light-induced ligand-to-metal charge transfer (LMCT) has been utilized as a powerful strategy in various organic reactions. First-row transition metals, especially iron complexes, show good applications in this process. Fe(III)-Cl and Fe(III)-OR species are two key intermediates involved in the LMCT of iron complexes. This review highlights studies on LMCT of Fe(III)-OR species, including carboxylate-iron and alkoxy-iron species, in organic transformations. Reaction conditions, substrate scope and related mechanisms are discussed.

Conjugated Polymers Based on Carbazole and Tridentate Ligands as the "On-Off-On" Fluorescent Probes for Detection of Ni (II) Ion and Lysine.

Two novel conjugated polymers (polymer 1 and polymer 2) containing trisheterocyclic systems and carbazole as the copolymerization unit were synthesized by the Suzuki coupling reaction and characterized using NMR spectroscopy and other methods. 4'-(3,5-Dibromophenyl)-2,2':6',2''-terpyridine and 2,2'-(4-(3,5-dibromophenyl)pyridine-2,6-diyl)dithiazole were used as the recognizing units of the two polymers respectively. The polymers show blue-violet fluorescence when dissolved in THF. The ability of the polymers to identify anions and metal ions was investigated by fluorescence sensing tests. It was found that I- not only quenched the fluorescence but also undergone some redshift. Ni (II) efficiently quenched the fluorescence of the polymers, and polymer 2 recognized Ni2+ with higher specificity. UV-visible absorption titration experiments showed that Ni2+ formed complexes with the polymers. In addition, the formation of complexes between Ni2+ and polymers were used for the detection of amino acids, and it was found that lysine could regenerate the fluorescence of [polymer 1-Ni2+] and [polymer 2-Ni2+] with 99% fluorescence recovery.

Laparoscopic orchidopexy for the treatment of cryptorchidism in adults: a description of the technique and outcomes.

BACKGROUND: There are few studies on cryptorchidism in adults, and its treatment is still controversial. METHODS: To summarize the surgical strategy and clinical efficacy of laparoscopic orchidopexy for the treatment of cryptorchidism in adults, 37 adult cryptorchidism patients were retrospectively analyzed between September 2017 and February 2022. All 37 patients underwent laparoscopic orchidopexy, of whom 33 underwent inguinal hernia repair without tension. The intraoperative procedures and surgical techniques were recorded in detail. Preoperative examination and regular postoperative review of color Doppler ultrasound, and reproductive hormone, alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase levels were performed. RESULTS: All testes descended successfully into the scrotum, including 25 through the inguinal route and 12 through Hesselbach's triangle route. No intraoperative or postoperative complications were observed. The follow-up time was 38.6 (± 19.4) months, and no evidence of testicular malignancy was found during the follow-up period. After analyzing the reproductive hormone levels at 1 year postoperatively in 28 patients with more than 1 year of follow-up, it was found that the patients had a significant increase in testosterone levels and a decrease in follicle-stimulating hormone levels after surgery. None of the patients showed any significant improvement in semen quality after surgery. CONCLUSION: Our study suggests that laparoscopic orchidopexy is a safe and feasible surgical procedure for the treatment of cryptorchidism in adults, especially high cryptorchidism, which is difficult to treat. After comprehensive consideration, preserving the testis should be preferred for treating cryptorchidism in adults to maximize the protection of the patient's reproductive hormone secretion function.

Dual roles of dopaminergic pathways in olfactory learning and memory in the oriental fruit fly, Bactrocera dorsalis.

Dopamine (DA) is a key regulator of associative learning and memory in both vertebrates and invertebrates, and it is widely believed that DA plays a key role in aversive conditioning in invertebrates. However, the idea that DA is involved only in aversive conditioning has been challenged in recent studies on the fruit fly (Drosophila melanogaster), ants and crabs, suggesting diverse functions of DA modulation on associative plasticity. Here, we present the results of DA modulation in aversive olfactory conditioning with DEET punishment and appetitive olfactory conditioning with sucrose reward in the oriental fruit fly, Bactrocera dorsalis. Injection of DA receptor antagonist fluphenazine or chlorpromazine into these flies led to impaired aversive learning, but had no effect on the appetitive learning. DA receptor antagonists impaired both aversive and appetitive long-term memory retention. Interestingly, the impairment on appetitive memory was rescued not only by DA but also by octopamine (OA). Blocking the OA receptors also impaired the appetitive memory retention, but this impairment could only be rescued by OA, not by DA. Thus, we conclude that in B. dorsalis, OA and DA pathways mediate independently the appetitive and aversive learning, respectively. These two pathways, however, are organized in series in mediating appetitive memory retrieval with DA pathway being at upstream. Thus, OA and DA play dual roles in associative learning and memory retrieval, but their pathways are organized differently in these two cognitive processes - parallel organization for learning acquisition and serial organization for memory retrieval.

Nonlinear-mirror mode-locked crystal waveguide laser by intracavity fourth-harmonic loss modulation.

We present a nonlinear-mirror (NLM) mode-locked crystal waveguide laser. By adding nonlinear crystals into traditional NLM devices, the fourth harmonic is generated to form loss modulation, which suppresses the Q-switching instability of mode-locked lasers and achieves the optimal equivalent transmittance. The NLM mode-locked laser delivers ∼30 W average power with a repetition rate of 32.2 MHz and a pulse width of 950 fs. It is revealed that this novel, to the best of our knowledge, design with simple, robust, and reliable structure has a great potential in the development of high-power mode-locked laser.

A Poly(carbazole-alt-triazole) with Thiabendazole Side Groups as an "On-Off-On" Fluorescent Probe for Detection of Cu(II) Ion and Cysteine.

A novel conjugated polymer PCZBTA-TBZ containing thiabendazole as recognition unit was synthesized via Suzuki coupling reaction, and its structural characterization, spectroscopic analysis and photophysical properties were investigated. In the metal ion response study, the addition of Cu2+ led to the occurrence of the photoinduced electron transfer (PET) mechanism, which significantly quenched the fluorescence of the polymer PCZBTA-TBZ with a quenching effect of 98%. Furthermore, I- can significantly quench the fluorescence of the polymer, but other anions have no such effect. According to the density functional theory calculation, compared with other polycarbazoles or other alternative copolymers containing carbazole, with alternating carbazole and triazole enhances the electron mobility and reduces the energy band gap of the polymer. Due to the strong coordination ability between Cu2+ and Cys, the adding Cys competes the Cu2+ in the [PCZBTA-TBZ-Cu2+] complex, blocking the occurrence of PET, and the fluorescence intensity of PCZBTA-TBZ is restored. The addition of other amino acids caused almost no change. The polymer is expected to be used for dual fluorescence detection of specific metal ions and Cys.

Evaluating hs-cTnI serum levels and cTnI gene expression compared with cardiac nuclear scan in patients with angina pectoris.

Exercise stress can cause reversible myocardial ischemia in people with coronary artery disease (CAD). On the other hand, the new troponin biomarker with high sensitivity can detect faster and small amounts of troponin in blood circulation. The present study aimed to investigate the serum troponin level following exercise stress and the result of nuclear heart scans as the gold standard. For this purpose, 93 patients with stable angina and no history of known CAD and organic disease were included in this cross-sectional study. The serum level of the highly sensitive cardiac troponin I (hs-cTnI) was measured 75 minutes after the peak of the exercise test and reached at least 85% of the maximum heart rate. It was compared with the rate of reversible myocardial ischemia based on the nuclear heart scan, the three-month prognosis and the persistence of chest pain were investigated. Also, the expression level of the cTnI gene was evaluated by real-time PCR technique. The results showed that the average age of the patients was 58.9+12.4 years, and 62 (66.66%) patients were female. Reversible myocardial ischemia was observed in 31 patients. The relationship between hs-cTI level and the rate of reversible ischemia cases was significant (p = 0.0041). Also, the cTnI gene expression showed the same results as the serum level. According to the heart nuclear scan report, the hs-cTnI value above 1.6ng/dl had a specificity of 72% and sensitivity of 66%, a positive predictive value of 53%, and a negative predictive value of 78%. There was no significant relationship between hs-cTnI level and prognosis and the continuation of chest pain in patients after three months. Generally, the serum level of high-sensitivity cardiac troponin was higher after exercise in the group with reversible myocardial ischemia.

The normalization of the active surface sites of bimetallic Pd-Pt catalysts, their inhomogeneity, and their roles in methane activation.

Multi-metallic catalysts containing Pt species are widely used. As there is no methodology to evaluate the quantity of active surface sites of Pt or other metal species, researchers have only published the total conversion or selectivity of all active surface sites. This study focuses on Pt-Pd bimetallic catalysts and uses both methane reaction kinetics and infrared (IR) spectroscopy to characterize the surface Pd and Pt sites. The surface Pt sites, which were determined from the fitted rate coefficients, were evaluated in the reaction region where the catalyst structure was insensitive to catalytic performance. Another methodology involves IR spectroscopy to normalize the active surface sites. As three typical absorption bands of Pt species were observed during CO chemisorption, spectral deconvolution was conducted to obtain the integrated intensity of the Pd and Pt species, and the quantity of surface Pd and Pt sites was calculated. The two methods have good consistency, and the IR spectra are considered to be more suitable for calculating the quantity of active surface sites. In addition, the IR spectra revealed a correlation between oxidative Pd surface sites and methane reactivity. The ionic Pd sites provide abundant oxygen intermediates in the catalytic reaction and improve the catalytic performance. As for the surface Pd species and bulk Pd species, the XPS results indicate a similar variation in the Pdδ+/(Pdδ+ + Pd0) ratio vs. Pd/Pt ratio.

Dual-wavelength laser source by spectral beam combining of two Nd:YAG pulse lasers.

We present a dual-wavelength laser source obtained by spectral beam combining of two solid-state Nd:YAG pulsed lasers. The central wavelengths were locked at 1061.5 and 1064.6 nm. The output energy was the sum of the energy of the individually locked Nd:YAG lasers. The beam quality M 2 of the combined beam is 2.8×2.2, which is nearly the same as that of a single Nd:YAG laser beam. This work should be helpful to provide an effective dual-wavelength laser source for applications.

Analysis of genetic diversity and selection signals in Chaling cattle of southern China using whole-genome scan.

China has diversified resources of indigenous cattle, which are classified into Northern, Central, and Southern groups according to their geographical distribution. Chaling cattle belong to Southern group. This breed is famous for the production of good quality meat with elite meat grades. To analyze the genetic diversity of Chaling cattle, 20 samples were sequenced using whole-genome resequencing technology, along with 138 published whole-genome sequencing data of Indian indicine cattle, Chinese indicine cattle, East Asian taurine cattle, Eurasian taurine cattle, and European taurine cattle as control. It was found that Chaling cattle originated from Chinese indicine cattle. The genetic diversity of Chaling cattle is higher than that of Indian indicine cattle, East Asian taurine cattle, Eurasian taurine cattle, and European taurine cattle, but lower than that of Chinese indicine cattle and Xiangxi cattle. Annotating the selection signals obtained by composite likelihood ratio, θπ, FST , π-ratio, and XP-EHH methods, several genes associated with immunity, heat tolerance, reproduction, growth, and meat quality showed strong selection signals. In general, this study provides a theoretical basis for analyzing the genetic mechanism of Chaling cattle with excellent adaptability, rough feeding tolerance, good immune performance, and good meat quality. This work lays a foundation for genetic breeding of Chaling cattle in future.

COVID-19 Research in Communication Journals: A Structural Topic Modeling-Assisted Bibliometric Analysis.

This article presents a bibliometric analysis of research on COVID-19 health communication. We reviewed and analyzed 1,851 articles published in 170 peer-reviewed communication journals between January 2020 and November 2022, to identify key bibliometric information and major research topics in this rapidly expanding field of research. The distribution of countries indicates that the United States is the most productive country, and researchers from Spain, China and the United Kingdom also play an important role. Health Communication is the most influential journal in terms of research productivity and impact. The analysis of highly cited references demonstrates the interdisciplinary nature of this research field. The topics generated by structural topic modeling show that scholars have responded to a variety of issues in COVID-19 communication, encompassing different levels of health communication, the effects of information dissemination, the impact on the general public as well as vulnerable populations, health preventive behaviors and communication technologies. This study aims to enhance researchers' understanding of the current state of this research field and provide insights for future studies.

Influencing factors for residual kidney function in incident peritoneal dialysis patients: a systematic review and meta-analysis.

BACKGROUND: Residual kidney function (RKF) impacts patients' survival rate and quality of life when undergoing peritoneal dialysis (PD). This meta-analysis was conducted to systematically identify risk and protective factors associated with RKF decline and loss. METHODS: We searched three English and one Chinese databases from inception to January 31, 2023, for cohort and cross-sectional studies exploring factors associated with RKF decline or loss. The random effects model was employed to aggregate risk estimates and 95% confidence intervals (CIs) from multivariate analysis. Sensitivity and subgroup analyses were performed to explore the heterogeneity among the studies. RESULTS: Twenty-seven studies comprising 13549 individuals and 14 factors were included in the meta-analysis. Based on the meta-analysis results, risk factors involving male gender (hazard ratio (HR) 1.689, 95%CI 1.385-2.061), greater body mass index (BMI) (odds ratio (OR) 1.081, 95% confidence interval (CI) 1.029-1.135), higher systolic blood pressure (SBP) (HR 1.014, 95%CI 1.005-1.024), diabetes mellitus (DM) (HRRKF loss 1.873, 95%CI 1.475-2.378), DM (ORRKF decline 1.906, 95%CI 1.262-2.879), peritonitis (relative ratio (RR) 2.291, 95%CI 1.633-3.213), proteinuria (OR 1.223, 95%CI 1.117-1.338), and elevated serum phosphorus (RR 2.655, 95%CI 1.679-4.201) significantly contributed to the risk of RKF decline and loss in PD patients. Conversely, older age (HR 0.968, 95%CI 0.956-0.981), higher serum albumin (OR 0.834, 95%CI 0.720-0.966), weekly Kt/V urea (HR 0.414, 95%CI 0.248-0.690), baseline urine volume (UV) (HR 0.791, 95%CI 0.639-0.979), baseline RKF (HR 0.795, 95%CI 0.739-0.857) exhibited protective effects. However, diuretics use, automatic peritoneal dialysis (APD) modality and baseline RKF did not significantly impact RKF decline. CONCLUSIONS: Patients with male gender, greater BMI, higher SBP, DM, peritonitis, proteinuria, and elevated serum phosphorus might have a higher risk of RKF decline and loss. In contrast, older age, higher serum albumin, weekly Kt/V urea, baseline UV, and baseline RKF might protect against RKF deterioration.

A Case of Giant Left Circumflex Coronary Fistula Aneurysm with Unidentified Fistula.

A coronary aneurysm is a rare type of cardiovascular disease. We report a case of a 53-year-old male patient who presented to our hospital with a giant left circumflex coronary fistula aneurysm (LCCA) (75 mm × 70 mm). Since coronary angiography and coronary computed tomography angiography failed to detect the fistula of the coronary aneurysm, interventional occlusion surgery could not be performed. We discovered the fistula in the right atrium by anterograde perfusion with blood-containing myocardial protective fluid after switching to intraoperative exploration during cardiac surgery. The coronary aneurysm's fistula and inlet were then sutured, and the aneurysm was resected. The patient recovered successfully after the operation. This case was instructive in managing LCCA, especially with an unidentified fistula.