Femtosecond pulse generation from a SESAM mode-locked Tm,Ho:SrF2 laser at 2.08 µm.

We report on a passively mode-locked Tm,Ho:SrF2 laser employing a SESAM as saturable absorber (SA), delivering nearly Fourier-transform-limited 246 fs pulses at 2084nm without any additional intra- or extra-cavity dispersion compensation elements. This represents, to the best of our knowledge, the shortest pulses generated from the mode-locked fluoride bulk lasers in the 2-µm spectral range. Such compact femtosecond laser can be a potential seed source for large-sized fluoride bulk amplifier systems with exact gain match, enabling the generation of ultrashort intense pulses around 2 µm.

Tunable and mode-locked Tm,Ho:GdScO3 laser.

A novel, to the best of our knowledge, Tm,Ho:GdScO3 crystal grown using the Czochralski method was investigated for its polarized spectroscopic properties and laser performance in both tunable continuous-wave (CW) and mode-locked regimes. The crystal's multisite structure (Gd3+/Sc3+ site) and Tm3+/Ho3+ dopants contributed to spectral broadening, enabling a tunable laser operation from 1914 to 2125 nm (with a broad range of 215 nm). Additionally, a pulse duration of 72 fs was achieved for E || b polarization. These results demonstrate the potential of the Tm,Ho:GdScO3 perovskite crystal as a promising gain material for ultrafast lasers operating around 2 µm.

Migration from Lysosome to Nucleus: Monitoring Lysosomal Alkalization-Related Biological Processes with an Aminofluorene-Based Probe.

Aberrant lysosomal alkalization is associated with various biological processes, such as oxidative stress, cell apoptosis, ferroptosis, etc. Herein, we developed a novel aminofluorene-based fluorescence probe named FAN to monitor the lysosomal alkalization-related biological processes by its migration from lysosome to nucleus. FAN possessed NIR emission, large Stokes shift, high pH stability, and high photostability, making it suitable for real-time and long-term bioimaging. As a lysosomotropic molecule, FAN can accumulate in lysosomes first and then migrate to the nucleus by right of its binding capability to DNA after lysosomal alkalization. In this manner, FAN was successfully used to monitor these physiological processes which triggered lysosomal alkalization in living cells, including oxidative stress, cell apoptosis, and ferroptosis. More importantly, at higher concentrations, FAN could also serve as a stable nucleus dye for the fluorescence imaging of the nucleus in living cells and tissues. This novel multifunctional fluorescence probe shows great promise for application in lysosomal alkalization-related visual research and nucleus imaging.

Mode-locking of a Tm,Ho:CALYGO laser delivering 50 fs pulses at 2.08 µm.

We study the polarization-dependent laser performance of a novel, to the best of our knowledge, "mixed" Tm,Ho:CaYGdAlO4 crystal in the continuous-wave (CW) and mode-locked regimes. Both in terms of the CW tunability range (261 nm) and the minimum pulse duration (50 fs at 2078 nm, spectral width of 95 nm) in the mode-locked regime, σ-polarization is superior. With extended inhomogeneous spectral broadening due to structural and compositional disorder, Tm,Ho:CaYGdAlO4 is promising for few-optical-cycle pulse generation around 2 µm.

Risk single-nucleotide polymorphism-mediated enhancer-promoter interaction drives keloids through long noncoding RNA down expressed in keloids.

BACKGROUND: Keloids represent one extreme of aberrant dermal wound healing and are characterized by fibroblast hyperproliferation and excessive deposition of extracellular matrix. Genetics is a major factor for predisposition to keloids and genome-wide association study has identified a single-nucleotide polymorphism (SNP) rs873549 at 1q41 as a susceptibility locus. The SNP rs873549, and the SNPs in strong linkage disequilibrium (LD) with rs873549, may be involved in keloid development. However, the functional significance of these SNPs in keloid pathogenesis remains elusive. OBJECTIVES: To investigate the function and mechanism of SNP rs873549 and the SNPs in strong LD with rs873549 in keloids. METHODS: SNPs in strong LD with rs873549 were analysed using Haploview. The expression levels of the genes near the susceptibility locus were analysed using quantitative real-time polymerase chain reaction. The interaction between rs1348270-containing enhancer and the long noncoding RNA down expressed in keloids (DEIK) (formerly RP11-400N13.1) promoter in fibroblasts was investigated using chromosome conformation capture. The enhancer activity of the rs1348270 locus was evaluated using luciferase reporter assay. Knockdown experiments were used to explore the function of DEIK in keloids. RNA-Seq was performed to investigate the mechanism by which DEIK regulates the expression of collagens POSTN and COMP. RESULTS: rs1348270, an enhancer-located SNP in strong LD with rs873549, mediated looping with the promoter of DEIK. The risk variant was associated with decreased enhancer-promoter interaction and DEIK down-expression in keloids. Mechanistically, downregulation of DEIK increased the expression of collagens POSTN and COMP through upregulating BMP2. Furthermore, correlation analysis revealed that DEIK expression was inversely correlated with BMP2, POSTN and COMP expression in both keloid and normal fibroblasts. CONCLUSIONS: Our findings suggest that the risk variant rs1348270 is located in an enhancer and is associated with the downregulation of DEIK in keloids, and that downregulation of DEIK increases the expression of collagens POSTN and COMP through BMP2 in keloid fibroblasts. These findings will help to provide a more thorough understanding of the role played by genetic factors in keloid development and may lead to new strategies for screening and therapy in keloid-susceptible populations.

An Open-Label, Uncontrolled, Single-Arm Clinical Trial of Tofacitinib, an Oral JAK1 and JAK3 Kinase Inhibitor, in Chinese Patients with Keloid.

BACKGROUND: The keloid treatment is still a thorny and complicated clinical problem, especially in multiple keloids induced by wound, severe burn, ethnic background or cultural behaviors, or unexplained skin healing. Mainstream treatments have limited efficacy in treating multiple keloids. As no oral treatment with painlessness and convenience is available, oral treatment strategies should be formulated. OBJECTIVES: This study aimed to investigate the efficacy and therapeutic mechanism of oral tofacitinib in keloid patients. METHODS: We recruited the 7 patients with keloid scars and prescribed 5 mg of tofacitinib twice a day orally with a maximum follow-up of 12 weeks. The Patient and Observer Scar Assessment Scale (POSAS), the Vancouver scar scale (VSS), ANTERA 3D camera, and the DUB Skin Scanner 75 were used to assess the characteristics of the lesion. Immunohistochemistry was performed to evaluate collagen synthesis, proliferation, and relative molecular pathways. Moreover, the effects of tofacitinib were assessed on keloid fibroblast in vitro. RESULTS: After 12 weeks of oral tofacitinib, significant improvement in POSAS, VSS, and Dermatology Life Quality Index (DLQI) scores was observed (p < 0.05). The volume, lesion height, and dermis thickness of the keloid decreased (p < 0.05). Moreover, significant decreases in the expression of collagen I, Ki67, p-STAT 3, and p-SMAD2 were observed after 12 weeks of administration. In vitro experiments suggested that tofacitinib treatment inhibits fibroblast proliferation and collagen I synthesis via suppression of STAT3 and SMAD2 pathway. CONCLUSION: Tofacitinib, a new candidate oral drug for keloid, could reduce keloid lesion volume by inhibiting collagen synthesis and inhibiting fibroblast proliferation, and alleviate itch and pain to obtain a better life quality.

Age-specific spectrum of etiological pathogens for viral diarrhea among children in twelve consecutive winter-spring seasons (2009-2021) in China.

Viral diarrhea is one of the leading causes of morbidity and mortality in children. This study was conducted to disclose the etiological cause and epidemiological features of viral diarrhea among children in China. From 2009 to 2021, active surveillance was performed on pediatric patients with acute diarrhea and tested for five enteric viruses. Positive detection was determined in 65.56% (3325/5072) patients and an age-specific infection pattern was observed. A significantly higher positive rate was observed in 12-23-month-old children for rotavirus (47.46%) and adenovirus (7.06%), while a significantly higher positive rate was observed for norovirus (37.62%) in 6-11-month-old patients, and for astrovirus (11.60%) and sapovirus (10.79%) in 24-47-month-old patients. A higher positive rate of rotavirus in girls and norovirus in boys was observed only among 6-11 months of patients. We also observed more norovirus among patients from rural areas in the 0-5- and 36-47-month groups and more rotavirus among those from rural areas in the 12-23-month group. Diarrhea severity was greater for rotavirus in the 6-23-month group and norovirus in the 6-11-month group. Coinfections were observed in 29.26% (973/3325) of positive patients, and were most frequently observed between rotavirus and others (89.31%). Our findings could help the prediction, prevention, and potential therapeutic approaches to viral diarrhea in children.

Preclinical safety and hepatotoxicity evaluation of biomineralized copper sulfide nanoagents.

Albumin-biomineralized copper sulfide nanoparticles (Cu2-xS NPs) have attracted much attention as an emerging phototheranostic agent due to their advantages of facile preparation method and high biocompatibility. However, comprehensive preclinical safety evaluation is the only way to meet its further clinical translation. We herein evaluate detailedly the safety and hepatotoxicity of bovine serum albumin-biomineralized Cu2-xS (BSA@Cu2-xS) NPs with two different sizes in rats. Large-sized (LNPs, 17.8 nm) and small-sized (SNPs, 2.8 nm) BSA@Cu2-xS NPs with great near-infrared absorption and photothermal conversion efficiency are firstly obtained. Seven days after a single-dose intravenous administration, SNPs distributed throughout the body are cleared primarily through the feces, while a large amount of LNPs remained in the liver. A 14-day subacute toxicity study with a 28-day recovery period are conducted, showing long-term hepatotoxicity without recovery for LNPs but reversible toxicity for SNPs. Cellular uptake studies indicate that LNPs prefer to reside in Kupffer cells, leading to prolonged and delayed hepatotoxicity even after the cessation of NPs administration, while SNPs have much less Kupffer cell uptake. RNA-sequencing analysis for gene expression indicates that the inflammatory pathway, lipid metabolism pathway, drug metabolism-cytochrome P450 pathway, cholesterol/bile acid metabolism pathway, and copper ion transport/metabolism pathway are compromised in the liver by two sizes of BSA@Cu2-xS NPs, while only SNPs show a complete recovery of altered gene expression after NPs discontinuation. This study demonstrates that the translational feasibility of small-sized BSA@Cu2-xS NPs as excellent nanoagents with manageable hepatotoxicity.

Lymph node metastasis pattern and significance of left gastric artery lymph node dissection in esophagectomy for esophageal cancers.

PURPOSE: To investigate the lymph node metastasis pattern and significance of dissection of the left gastric artery lymph nodes in radical en bloc esophagectomy for esophageal squamous carcinomas based on the lymphatic drainage pathway revealed by carbon nanoparticle labeling. MATERIALS AND METHODS: Patients who underwent en bloc esophagectomy endoscopically were retrospectively enrolled. Carbon nanoparticles were injected in the submucosa of upper thoracic esophagus to label the relevant draining lymph nodes. The clinical data, lymph nodes dissected, surgical technique, and complications were analyzed. RESULTS: En bloc esophagectomy was successful in all 179 patients. Metastases to the left gastric artery lymph nodes were positive in 42 patients (23.5%) but negative in 137 (76.5%). The left gastric lymph nodes were labeled, whereas no celiac lymph nodes were labeled by carbon nanoparticles. A total of 4652 lymph nodes were resected, with 26 lymph nodes per patient. Seventy-three patients had lymph node metastasis (73/179). Seventeen patients had metastasis to the recurrent laryngeal nerve lymph nodes (9.5%). The metastasis rate of the lower thoracic esophageal cancer to the left gastric artery lymph nodes was 37.0%, significantly greater than that at the middle (15.4%) or upper (6.7%) thoracic segment. The lymph node metastasis rate was significantly (P < 0.05) increased with the length of the cancerous lesion, infiltration depth, and poor differentiation. Univariate analysis revealed that the metastasis rate to the left gastric artery lymph nodes was significantly (P < 0.05) associated with paraesophageal lymph node metastasis, para-cardial lymph metastasis, and TNM classification. Multivariate analysis indicated that cancer location (odds ratio 8.32, 95% confidence interval 2.12-32.24) was significantly (P < 0.05) associated with metastasis to the left gastric artery lymph nodes, with the cancer at the middle and lower thoracic segments significantly more than in the upper thoracic segment. CONCLUSION: Certain patterns exist in lymph node metastasis of esophageal cancer, and in radical esophagectomy of esophageal cancers, dissection of the left gastric artery lymph nodes is necessary to prevent possible residual or metastasis of esophageal squamous carcinomas based on the lymphatic drainage pathway of esophageal carcinomas demonstrated by carbon nanoparticle labeling.

DNA prime and virus-like particle boost from a single H5N1 strain elicits broadly neutralizing antibody responses against head region of H5 hemagglutinin.

Since 1996, highly pathogenic avian influenza (HPAI) H5N1 virus has presented a persistent threat to public health. Its high degree of genetic diversity also poses enormous challenges in developing effective vaccines. To search for vaccine regimens that could elicit broadly neutralizing antibody responses against diverse HPAI H5N1 strains, in the present study we tested H5 hemagglutinin (HA) from an A/Thailand/1(KAN)-1/2004 strain in a heterologous prime-boost vaccination. We demonstrated that priming mice with DNA and boosting with virus-like particle induced antibody responses that cross-neutralize all reported clades and subclades of HPAI H5N1 viruses and protect mice from high lethal dose HPAI H5N1 challenge in both active and passive immunizations. Unexpectedly, cross-divergent H5 neutralizing antibodies are directed to the HA head and block both attachment and postattachment of virus entry. Thus, we conclude that as a promising pan-H5 vaccine candidate this prime-boost regimen could be further developed in ferrets and in humans.

Challenges and Strategies for Endothelializing Decellularized Small-Diameter Tissue-Engineered Vessel Grafts.

Vascular diseases are the leading cause of ischemic necrosis in tissues and organs, necessitating using vascular grafts to restore blood supply. Currently, small vessels for coronary artery bypass grafts are unavailable in clinical settings. Decellularized small-diameter tissue-engineered vessel grafts (SD-TEVGs) hold significant potential. However, they face challenges, as simple implantation of decellularized SD-TEVGs in animals leads to thrombosis and calcification due to incomplete endothelialization. Consequently, research and development focus has shifted toward enhancing the endothelialization process of decellularized SD-TEVGs. This paper reviews preclinical studies involving decellularized SD-TEVGs, highlighting different strategies and their advantages and disadvantages for achieving rapid endothelialization of these vascular grafts. Methods are analyzed to improve the process while addressing potential shortcomings. This paper aims to contribute to the future commercial viability of decellularized SD-TEVGs.

Novel manganese and nitrogen co-doped biochar based on sodium bicarbonate activation for efficient removal of bisphenol A: Mechanism insight and role analysis of manganese and nitrogen by combination of characterizations, experiments and density functional theory calculations.

A novel porous manganese and nitrogen co-doped biochar (Mn-N@SBC) was synthesized via one-step pyrolysis, utilizing loofah agricultural waste as the precursor and NaHCO3 as the activator. The behavior of bisphenol A adsorbed on Mn-N@SBC was evaluated using static batch adsorption experiments. Compared to direct manganese-nitrogen co-doping, co-doping based on NaHCO3 activation significantly increased the specific surface area (231 to 1027 m2·g-1) and adsorption capacity (15 to 351 mg·g-1). Wide pH (2-10) and good resistance to cation/anion, humic acid and actual water demonstrated the robust adaptability of Mn-N@SBC to environmental factors. The significantly reduced specific surface area after adsorption, adverse effects of ethanol and phenanthrene on the removal of bisphenol A, and theoretically predicted interaction sites indicated the primary adsorption mechanisms involved pore filling, hydrophobicity, and π-π-electron-donor-acceptor interaction. This work presented an approach to create high-efficiency adsorbents from agricultural waste, offering theoretical and practical guidance for the removal of pollutants.

Construction of a novel aminofluorene-based ratiometric near-infrared fluorescence probe for detecting carboxylesterase activity in living cells.

Herein, we constructed a novel aminofluorene-based fluorescence probe (FEN-CE) for the detection of carboxylesterase (CE) in living cells by a ratiometric near-infrared (NIR) fluorescence signal. FEN-CE with NIR emission (650 nm) could be hydrolyzed specifically by CE and transformed to FENH with the release of the self-immolative group, which exhibited a red-shifted emission peak of 680 nm. In addition, FEN-CE showed high selectivity for CE and was successfully used in the detection of CE activity in living cells through its ratiometric NIR fluorescence signals.

HIV-1 virus-like particles produced by stably transfected Drosophila S2 cells: a desirable vaccine component.

The development of a successful vaccine against human immunodeficiency virus type 1 (HIV-1) likely requires immunogens that elicit both broadly neutralizing antibodies against envelope spikes and T cell responses that recognize multiple viral proteins. HIV-1 virus-like particles (VLP), because they display authentic envelope spikes on the particle surface, may be developed into such immunogens. However, in one way or the other current systems for HIV-1 VLP production have many limitations. To overcome these, in the present study we developed a novel strategy to produce HIV-1 VLP using stably transfected Drosophila S2 cells. We cotransfected S2 cells with plasmids encoding HIV-1 envelope, Gag, and Rev proteins and a selection marker. After stably transfected S2 clones were established, HIV-1 VLP and their immunogenicity in mice were carefully evaluated. Here, we report that HIV-1 envelope proteins are properly cleaved, glycosylated, and incorporated into VLP with Gag. The amount of VLP released into culture supernatants is comparable to those produced by insect cells infected with recombinant baculoviruses. Moreover, cryo-electron microscopy tomography revealed average 17 spikes per purified VLP, and antigenic epitopes on the spikes were recognized by the broadly neutralizing antibodies 2G12, b12, VRC01, and 4E10 but not by PG16. Finally, mice primed with DNA and boosted with VLP in the presence of CpG exhibited anti-envelope antibody responses, including ELISA-binding, neutralizing, antibody-dependent cell-mediated cytotoxicity and antibody-dependent cell-mediated viral inhibition, as well as envelope and Gag-specific CD8 T cell responses. Thus, we conclude that HIV-1 VLP produced by the S2 expression system has many desirable features to be developed into a vaccine component against HIV-1.

Prevalence of chronic kidney disease in Jing adults in China: a village-based study.

AIM: Chronic kidney disease (CKD) is increasingly recognized as a predictor of end-stage renal and cardiovascular disease. There is no data on CKD prevalence in numerous minority communities of China such as the Guangxi Jing community. We determined CKD prevalence and related risk factors in Jing adults. METHODS: A stratified cluster random sampling method was used in this study comprising 757 Jing adults. Questionnaires, physical examinations and laboratory tests including measurements of urinary albumin and hematuria, were performed. Estimated glomerular filtration rate (eGFR) was calculated using the improved Chinese population MDRD formula. CKD-related risk factors were also examined. RESULTS: After standardization for age and gender, the prevalence of albuminuria, haematuria and eGFR < 60 ml/min per 1.73 m2 was 12.5%, 3.8% and 0.4%, respectively Overall CKD prevalence was 15.3%, while the awareness rate was only 11.6%. Females had a significantly higher (p < 0.05) prevalence of albuminuria, hematuria and eGFR < 60 ml/min compared to males. CKD prevalence tended to increase significantly (< 0.05) with increase in age. Using the standardized age and gender ratios, the prevalence of hypertension, diabetes, hyperlipidemia and hyperuricemia was 14.8%, 5.2%, 38% and 16.2%, respectively, with awareness of 41.0%, 41.2%, 6.6% and 0.9%. Prevalence of overweight or obesity status and metabolic syndrome was 12.1% and 3.0%. Females showed a significantly higher prevalence of hyperuricemia and obesity or overweight status. CKD prevalence was also significantly higher in people with risk diseases. Regression analysis showed that age, gender, hypertension, high cholesterol and diabetes were CKD-related risk factors, while culture (higher education level) was a protective factor. CONCLUSION: Jing adults showed a high CKD prevalence of 15.3%, with a low awareness rate of 11.6%. Older subjects and females were more susceptible with a high prevalence of hypertension, diabetes, hyperlipidemia, metabolic syndrome etc. being associated closely with CKD.

Polyphyllin I suppressed the apoptosis of intervertebral disc nucleus pulposus cells induced by IL-1ß by miR-503-5p/Bcl-2 axis.

BACKGROUND: There are no studies that have shown the role and underlying mechanism of Polyphyllin I (PPI)-mediated anti-apoptosis activity in nucleus pulposus cells (NPCs). The research aimed to evaluate the effects of PPI in interleukin (IL)-1ß-induced NPCs apoptosis in vitro. METHODS: Cell Counting Kit-8 (CCK-8) assay was used to detect cell viability, and cell apoptosis was evaluated by double-stained flow cytometry (FITC Annexin V/PI). The expression of miR-503-5p was quantified by real-time quantitative PCR (qRT-PCR), and the expression of Bcl-2, Bax, and cleaved caspase-3 was quantified by Western blot. Dual-luciferase reporter gene assay was used to detect the targeting relationship between miR-503-5p and Bcl-2. RESULTS: PPI at 40 µg·mL-1 markedly promoted the viability of NPCs (P < 0.01). Also, PPI inhibited apoptosis and reduction in proliferative activity induced by IL-1ß in the NPCs (P < 0.001, 0.01). PPI treatment significantly inhibited the expression of apoptosis-related protein Bax, cleaved caspase-3 (P < 0.05, 0.01), and enhanced the level of anti-apoptotic protein Bcl-2 (P < 0.01). The proliferative activity of NPCs was significantly decreased and the apoptosis rate of NPCs was increased under IL-1ß treatment (P < 0.01, 0.001). Moreover, miR-503-5p was highly expressed in IL-1ß-induced NPCs (P < 0.001). Furthermore, the effect of PPI on NPCs viability and apoptosis in IL-1ß treatment was dramatically reversed by the overexpression of miR-503-5p (P < 0.01, 0.01). The targeted binding of miR-503-5p to the 3'UTR of Bcl-2 mRNA was confirmed by dual-luciferase reporter gene assays (P < 0.05). In further experiments, compared with miR-503-5p mimics, the effects of PPI on IL-1ß-induced NPCs viability and apoptosis were greatly reversed by the co-overexpression of miR-503-5p and Bcl-2 (P < 0.05, 0.05). CONCLUSION: PPI suppressed the apoptosis of intervertebral disk (IVD) NPCs induced by IL-1ß via miR-503-5p/Bcl-2 molecular axis.

Mechanistic study for drug induced cholestasis using batch-fabricated 3D spheroids developed by agarose-stamping method.

Cell spheroid culture can recapitulate the tissue microstructure and cellular responses in vivo. While there is a strong need to understand the modes of toxic action using the spheroid culture method, existing preparation techniques suffer from low efficiency and high cost. Herein, we developed a metal stamp containing hundreds of protrusions for batch bulk preparation of cell spheroids in each well of the culture plates. The agarose matrix imprinted by the stamp can form an array of hemispherical pits, which facilitated the fabrication of hundreds of uniformly sized rat hepatocyte spheroids in each well. Chlorpromazine (CPZ) was used as a model drug to investigate the mechanism for drug induced cholestasis (DIC) by agarose-stamping method. Hepatocyte spheroids showed a more sensitive detection of hepatotoxicity compared to 2D and Matrigel-based culture systems. Cell spheroids were also collected for staining of cholestatic protein and showed a CPZ-concentration-dependent decrease of bile acid efflux related proteins (BSEP and MRP2) and tight junction (ZO-1). In addition, the stamping system successfully delineated the DIC mechanism by CPZ that may be associated with the phosphorylation of MYPT1 and MLC2, two central proteins in the Rho-associated protein kinase pathway (ROCK), which were significantly attenuated by ROCK inhibitors. Our results demonstrated a large-scale fabrication of cell spheroids by the agarose-stamping method, with promising benefits for exploring the mechanisms for drug hepatotoxic responses.

CCR2 is a host entry receptor for severe fever with thrombocytopenia syndrome virus.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus causing a high fatality rate of up to 30%. To date, the receptor mediating SFTSV entry remained uncharacterized, hindering the understanding of disease pathogenesis. Here, C-C motif chemokine receptor 2 (CCR2) was identified as a host receptor for SFTSV based on a genome-wide CRISPR-Cas9 screen. Knockout of CCR2 substantially reduced viral binding and infection. CCR2 enhanced SFTSV binding through direct binding to SFTSV glycoprotein N (Gn), which is mediated by its N-terminal extracellular domain. Depletion of CCR2 in C57BL/6J mouse model attenuated SFTSV replication and pathogenesis. The peripheral blood primary monocytes from elderly individuals or subjects with underlying diabetes mellitus showed higher CCR2 surface expression and supported stronger binding and replication of SFTSV. Together, these data indicate that CCR2 is a host entry receptor for SFTSV infection and a novel target for developing anti-SFTSV therapeutics.

Dynamics of neutralizing antibodies against severe fever with thrombocytopenia syndrome virus.

OBJECTIVES: Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging tick-borne bunyavirus with a high pathogenicity. Little is known about the longitudinal dynamics of the SFTSV-specific neutralizing antibody (NAb) and the related factors in patients with SFTS. METHODS: A prospective cohort study of patients with laboratory-confirmed SFTS were conducted. Antiglomerulonephritis-immunoglobulin G (anti-Gn-IgG) and NAb titers were examined in serially collected serum samples, and their dynamic features were analyzed. RESULTS: NAb was initially detected at 15 days after symptom onset in surviving patients with SFTS, with positive rates of 37.21% (16/43), whereas neither anti-Gn-IgG antibody nor NAb was detected in patients with fatal SFTS during their hospitalization. The NAb levels reached the peak at 2 months after symptom onset, and then gradually declined, with a rapid downward trend from 6 months to 4 years and a relatively slow downward trend from 5 to 10 years. There was a positive correlation between NAb and anti-Gn-IgG titers in surviving patients with SFTS (r = 0.699, P <0.001). Patients with a mild illness or low viral load experienced early NAb seroconversion. Six different dynamic patterns of NAb were noted in surviving patients. CONCLUSION: These data provide useful information regarding the dynamic changes in NAb in patients with SFTS during the acute and convalescent phases and the follow-up period.