Correction: Development of a Humanized Antibody with High Therapeutic Potential against Dengue Virus Type 2.

[This corrects the article DOI: 10.1371/journal.pntd.0001636.].

[Effect of Chlorambucil Combined with Ibrutinib on Mantle Cell Lymphoma Cell Line Jeko-1 and Its Related Mechanism].

OBJECTIVE: To investigate the toxic effect of chlorambucil combined with ibrutinib on mantle cell lymphoma (MCL) cell line Jeko-1 and its related mechanism. METHODS: The MCL cell line Jeko-1 was incubated with different concentrations of chlorambucil or ibrutinib or the combination of the two drugs, respectively. CCK-8 assay was used to detect the proliferation of the cells, and Western blot was used to measure the protein expression levels of BCL-2, caspase-3, PI3K, AKT and P-AKT. RESULTS: After Jeko-1 cells were treated with chlorambucil (3.125, 6.25, 12.5, 25, 50 µmol/L) and ibrutinib (3.125, 6.25, 12.5, 25, 50 µmol /L) alone for 24, 48, 72h respectively, the cell proliferation was inhibited in a time- and dose-dependent manner. Moreover, the two drugs were applied in combination at low doses (single drug inhibition rate<50%), and the results showed that the combination of two drugs had a more significant inhibitory effect (all P < 0.05). Compared with the control group, the apoptosis rate of the single drug group of chlorambucil (3.125, 6.25, 12.5, 25, 50 µmol/L) and ibutinib (3.125, 6.25, 12.5, 25, 50 µmol/L) was increased in a dose-dependent manner. The combination of the two drugs at low concentrations (3.125, 6.25, 12.5 µmol/L) could significantly increase the apoptosis rate compared with the corresponding concentration of single drug groups (all P < 0.05). Compared with control group, the protein expression levels of caspase-3 in Jeko-1 cells were upregulated, while the protein expression levels of BCL-2, PI3K, and p-AKT/AKT were downregulated after treatment with chlorambucil or ibrutinib alone. The combination of the two drugs could produce a synergistic effect on the expressions of the above-mentioned proteins, and the differences between the combination group and the single drug groups were statistically significant (all P < 0.05). CONCLUSION: Chlorambucil and ibrutinib can promote the apoptosis of MCL cell line Jeko-1, and combined application of the two drugs shows a synergistic effect, the mechanism may be associated with the AKT-related signaling pathways.

An alleviative effect of Lonicerae japonicae flos water extract against liver fibrogenesis in vitro and in vivo.

Lonicerae japonicae (L. japonicae) flos is a medical and food homology herb. This study investigated the phenolic acid and flavonoid contents in L. japonicae flos water extract solution (LJWES) and the preventive effects of LJWES against liver fibrogenesis via FL83B cells and rats. LJWES contains many polyphenols, such as chlorogenic acid, morin, and epicatechin. LJWES increased cell viability and decreased cytotoxicity in thioacetamide (TAA)-treated FL83B cells (75 mM) (p < .05). LJWES decreased (p < .05) gene expressions of Tnf-α, Tnfr1, Bax, and cytochrome c but upregulated Bcl-2 and Bcl-xl in TAA-treated cells; meanwhile, increased protein levels of P53, cleaved caspase 3, and cleaved caspase 9 in TAA treated cells were downregulated (p < .05) by LJWES supplementation. In vivo, results indicated that TAA treatment increased serum liver damage indices (alanine aminotransferase [ALT] and alkaline phosphatase [ALP]) and cytokines (interleukin-6 and transforming growth factor-ß1) levels and impaired liver antioxidant capacities (increased thiobarbituric acid reactive substance value but decreased catalase/glutathione peroxidase activities) in rats (p < .05) while LJWES supplementation amended (p < .05) them. Liver fibrosis scores, collagen deposition, and alpha-smooth muscle actin deposition in TAA-treated rats were also decreased by LJWES supplementation (p < .05). To sum up, LJWES could be a potential hepatoprotective agent against liver fibrogenesis by enhancing antioxidant ability, downregulating inflammation in livers, and reducing apoptosis in hepatocytes.

A functional chicken-liver hydrolysate-based supplement ameliorates alcohol liver disease via regulation of antioxidation, anti-inflammation, and antiapoptosis.

Tons of broiler livers are produced yearly in Taiwan but always considered waste. Our team has successfully patented and characterized a chicken-liver hydrolysate (CLH) with several biofunctions. Chronic alcohol consumption causes hepatosteatosis or even hepatitis, cirrhosis, and cancers. This study was to investigate the hepatoprotection of CLH-based supplement (GBHP01™) against chronic alcohol consumption. Results showed that GBHP01™ could reduce (p < .05) enlarged liver size, lipid accumulation/steatosis scores, and higher serum AST, ALT, γ-GT, triglyceride, and cholesterol levels induced by an alcoholic liquid diet. GBHP01™ reduced liver inflammation and apoptosis in alcoholic liquid-diet-fed mice via decreasing TBARS, interleukin-6, interleukin-1ß, and tumor necrosis factor-α levels, increasing reduced GSH/TEAC levels and activities of SOD, CAT and GPx, as well as downregulating CYP2E1, BAX/BCL2, Cleaved CASPASE-9/Total CASPASE-9 and Active CASPASE-3/Pro-CASPASE-3 (p < .05). Furthermore, GBHP01™ elevated hepatic alcohol metabolism (ADH and ALDH activities) (p < .05). In conclusion, this study prove the hepatoprotection of GBHP01™ against alcohol consumption.

Comparative study of arterial and venous grafting for pedicle lengthening in head and neck microvascular reconstruction.

BACKGROUND: In the field of head and neck microvascular reconstruction, no previous study has compared arterial and venous grafting as methods of anterolateral thigh (ALT) pedicle lengthening. Therefore, we conducted this comparative study to compare the outcomes between the two pedicle lengthening techniques. METHODS: We performed comparative effectiveness research by conducting a retrospective chart review from January 2012 to December 2021 to identify patients who underwent head and neck reconstruction with non-descending branch ALT perforator flaps using either the in situ pedicle lengthening (ISPL) technique or the vein graft (VG) technique. A total of 26 patients were analyzed, including 14 who underwent ISPL, and 12 who underwent VG. The collected data, including patient demographics, surgical indications, history of prior free flap, prior neck dissection, radiation therapy, chemotherapy, graft length, and flap outcomes, were analyzed. The flap outcomes were categorized as total flap loss, partial flap loss, flap compromise that required operating room visits, or minor issues, including infection or dehiscence. The flap characteristics and postoperative outcomes were compared between the two groups. RESULTS: The VG group had two flap losses, whereas the ISPL group had none. Although the failure rate was higher in the VG group than that in the ISPL group, the difference was not statistically significant (0% vs. 16.7%, p = 0.203). Additionally, there were no significant differences in flap take-back (14.3% vs. 16.7%, p = 1) and minor complications between the two groups (35.7% vs. 33.3%, p = 1). CONCLUSIONS: If pedicle lengthening with vessel graft is inevitable in head and neck reconstruction, arterial graft may provide a reliable outcome and may be considered an effective alternative when compared to vein grafts.

Andrographolide Attenuates Oxidized LDL-Induced Activation of the NLRP3 Inflammasome in Bone Marrow-Derived Macrophages and Mitigates HFCCD-Induced Atherosclerosis in Mice.

Andrographolide (AND) is a bioactive component of the herb Andrographis paniculata and a well-known anti-inflammatory agent. Atherosclerosis is a chronic inflammatory disease of the vasculature, and oxidized LDL (oxLDL) is thought to contribute heavily to atherosclerosis-associated inflammation. The aim of this study was to investigate whether AND mitigates oxLDL-mediated foam cell formation and diet-induced atherosclerosis (in mice fed a high-fat, high-cholesterol, high-cholic acid [HFCCD] diet) and the underlying mechanisms involved. AND attenuated LPS/oxLDL-mediated foam cell formation, IL-1[Formula: see text] mRNA and protein (p37) expression, NLR family pyrin domain containing 3 (NLRP3) mRNA and protein expression, caspase-1 (p20) protein expression, and IL-1[Formula: see text] release in BMDMs. Treatment with oxLDL significantly induced protein and mRNA expression of CD36, lectin-like oxLDL receptor-1 (LOX-1), and scavenger receptor type A (SR-A), whereas pretreatment with AND significantly inhibited protein and mRNA expression of SR-A only. Treatment with oxLDL significantly induced ROS generation and Dil-oxLDL uptake; however, pretreatment with AND alleviated oxLDL-induced ROS generation and Dil-oxLDL uptake. HFCCD feeding significantly increased aortic lipid accumulation, ICAM-1 expression, and IL-1[Formula: see text] mRNA expression, as well as blood levels of glutamic pyruvic transaminase (GPT), total cholesterol, and LDL-C. AND co-administration mitigated aortic lipid accumulation, the protein expression of ICAM-1, mRNA expression of IL-1[Formula: see text] and ICAM-1, and blood levels of GPT. These results suggest that the working mechanisms by which AND mitigates atherosclerosis involve the inhibition of foam cell formation and NLRP3 inflammasome-dependent vascular inflammation as evidenced by decreased SR-A expression and IL-1[Formula: see text] release, respectively.

Human ACE2 protein is a molecular switch controlling the mode of SARS-CoV-2 transmission.

BACKGROUND: Human angiotensin-converting enzyme 2 (hACE2) is the receptor mediating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. hACE2 expression is low in the lungs and is upregulated after SARS-CoV-2 infection. How such a hACE2-limited pulmonary environment supports efficient virus transmission and how dynamic hACE2 expression affects SARS-CoV-2 infection are unclear. METHODS: We generated stable cell lines with different expression levels of hACE2 to evaluate how the hACE2 expression level can affect SARS-CoV-2 transmission. RESULTS: We demonstrated that the hACE2 expression level controls the mode of SARS-CoV-2 transmission. The hACE2-limited cells have an advantage for SARS-CoV-2 shedding, which leads to cell-free transmission. By contrast, enhanced hACE2 expression facilitates the SARS-CoV-2 cell-to-cell transmission. Furthermore, this cell-to-cell transmission is likely facilitated by hACE2-containing vesicles, which accommodate numerous SARS-CoV-2 virions and transport them to neighboring cells through intercellular extensions. CONCLUSIONS: This hACE2-mediated switch between cell-free and cell-to-cell transmission routes provides SARS-CoV-2 with advantages for either viral spread or evasion of humoral immunity, thereby contributing to the COVID-19 pandemic and pathogenesis.

Broadly neutralizing human antibodies against Omicron subvariants of SARS-CoV-2.

BACKGROUND: The COVID-19 pandemic continues to pose a significant worldwide threat to human health, as emerging SARS-CoV-2 Omicron variants exhibit resistance to therapeutic antibodies and the ability to evade vaccination-induced antibodies. Here, we aimed to identify human antibodies (hAbs) from convalescent patients that are potent and broadly neutralizing toward Omicron sublineages. METHODS: Using a single B-cell cloning approach, we isolated BA.5 specific human antibodies. We further examined the neutralizing activities of the most promising neutralizing hAbs toward different variants of concern (VOCs) with pseudotyped virus. RESULTS: Sixteen hAbs showed strong neutralizing activities against Omicron BA.5 with low IC50 values (IC50 < 20 ng/mL). Among four of the most promising neutralizing hAbs (RBD-hAb-B22, -B23, -B25 and -B34), RBD-hAb-B22 exhibited the most potent and broad neutralization profiles across Omicron subvariant pseudoviruses, with low IC50 values (7.7-41.6 ng/mL) and a low PRNT50 value (3.8 ng/mL) in plaque assays with authentic BA.5. It also showed potent therapeutic effects in BA.5-infected K18-hACE2 mice. CONCLUSIONS: Thus, our efficient screening of BA.5-specific neutralizing hAbs from breakthrough infectious convalescent donors successfully yielded hAbs with potent therapeutic potential against multiple SARS-CoV-2 variants.

Natural fucoidans inhibit coronaviruses by targeting viral spike protein and host cell furin.

Fucoidans are a class of long chain sulfated polysaccharides and have multiple biological functions. Herein, four natural fucoidans extracted from Fucus vesiculosus, F. serratus, Laminaria japonica and Undaria pinnatifida, were tested for their HCoV-OC43 inhibition and found to demonstrate EC50 values ranging from 0.15 to 0.61 µg/mL. That from U. pinnatifida exhibited the most potent anti-HCoV-OC43 activity with an EC50 value of 0.15 ± 0.02 µg/mL, a potency largely independent of its sulfate content. Comparison of the gene expression profiles of fucoidan-treated and untreated cells infected with HCoV-OC43 revealed that fucoidan treatment effectively diminished HCoV-OC43 gene expressions associated with induced chemokines, cytokines and viral activities. Further studies using a highly fucoidan-resistant HCoV-OC43 determined that fucoidan inhibited HCoV-OC43 infection via interfering with viral entry and led to the identification of the specific site on the N-terminal region of spike protein, that located adjacent to the host cell receptor binding domain, targeted by the virus. Furthermore, in a SARS-CoV-2 pseudovirus neutralization assay, fucoidan also blocked SARS-CoV-2 entry. In vitro and in vivo, fucoidan decreased SARS-CoV-2 viral loads and inhibited viral infection in Calu-3 or Vero E6 cells and SARS-CoV-2 infected hamsters, respectively. Fucoidan was also found to inhibit furin activity, and reported furin inhibitors were found to inhibit viral infection by wild type HCoV-OC43 or SARS-CoV-2. Accordingly, we conclude that fucoidans inhibit coronaviral infection by targeting viral spike protein and host cell furin to interfere with viral entry.

Creating a context for recipient vessel selection in deep inferior epigastric perforator flap breast reconstruction.

BACKGROUND: In autologous tissue breast reconstruction, recipient vessels are important for artery perfusion and venous drainage to ensure free flap survival. There are insufficient clinical outcomes to select efficient recipient vessels in bi-pedicled deep inferior epigastric perforator (DIEP) flap reconstruction. METHODS: We presented a retrospective observational series of 108 patients regarding the diameter, anastomosis time, and re-anastomosis rate in internal mammary (IM), circumflex scapular (CS), thoracodorsal (TD), thoracoacromial (TA), lateral thoracic (LT), and internal mammary perforator (IMP) vessels of bi-pedicled DIEP flaps for breast reconstruction after mastectomy. The outcomes were the vessel re-anastomosis rate, flap failure rate, vessel anastomosis time, and complications. Data were gleaned from the chi-square test, Fisher's test, and analysis of variance using Scheffe's test as a post hoc analysis. The level of significance was p < 0.05. RESULTS: There were no significant differences in the diameters of the artery, first vein, and second vein across the recipient vessels (p > 0.05). However, the anastomosis time was longer in IM and TA than in CS, TD, and LT (p < 0.001). Also, there were no significant differences for re-anastomosis, flap necrosis, and fat necrosis among different recipient vessels (p > 0.05). CONCLUSIONS: Because of the altered mastectomy incisions, this study provides complete anatomical vascular properties and suggests that altering recipient vessel selection for bi-pedicled DIEP flaps can shorten anastomosis time and better conceal scars.

The psychological and physiological effects of integrated cognitive-behavioral and biofeedback therapy on panic disorder: A randomized controlled trial.

BACKGROUND: Cognitive-behavioral therapy (CBT) and biofeedback therapy are commonly regarded as effective treatment modalities for panic disorder. The aim of this study was to establish a Taiwanese version of an integrated cognitive-behavioral and biofeedback therapy (ICB) and examine its effects on panic disorder using psychological and physiological indicators. METHODS: Thirty patients with panic disorder were enrolled in this study. They were randomly assigned to either the ICB group (n = 15) or the treatment as usual (TAU) group (n = 15). The intervention consisted of six sessions, conducted once a week. Psychological indicators were measured at baseline (prior to intervention), week 3, and week 6, while physiological indicators were measured at baseline and week 6. The psychological indicators included five scales, with the Panic Disorder Severity Scale (PDSS) being the primary measure. The physiological indicators included respiratory sinus arrhythmia (RSA) and skin conductance, which respectively represent parasympathetic and sympathetic activity. RESULTS: Considering all participants, PDSS scores significantly decreased over time, but the difference between the ICB and TAU groups did not reach statistical significance. Among the physiological indicators, resting-state RSA and RSA under relaxation showed significant between-group differences over time, with the ICB group demonstrating a more pronounced improvement in RSA. CONCLUSION: In the context of existing pharmacological treatments, the benefits of ICB for panic disorder may not be observable through psychological indicators. However, it can lead to enhancement of parasympathetic activity as evidenced by the physiological indicators.

Competitive gamification in crowdsourcing-based contextual-aware recommender systems.

During the COVID-19 outbreak, crowdsourcing-based context-aware recommender systems (CARS) which capture the real-time context in a contactless manner played an important role in the "new normal". This study investigates whether this approach effectively supports users' decisions during epidemics and how different game designs affect users performing crowdsourcing tasks. This study developed a crowdsourcing-based CARS focusing on restaurant recommendations. We used four conditions (control, self-competitive, social-competitive, and mixed gamification) and conducted a two-week field study involving 68 users. The system provided recommendations based on real-time contexts including restaurants' epidemic status, allowing users to identify suitable restaurants to visit during COVID-19. The result demonstrates the feasibility of crowdsourcing to collect real-time information for recommendations during COVID-19 and reveals that a mixed competitive game design encourages both high- and low-performance users to engage more and that a game design with self-competitive elements motivates users to take on a wider variety of tasks. These findings inform the design of restaurant recommender systems in an epidemic context and serve as a comparison of incentive mechanisms for gamification of self-competition and competition with others.

Neutralizing antibodies targeting a novel epitope on envelope protein exhibited broad protection against flavivirus without risk of disease enhancement.

BACKGROUND: Flavivirus causes many serious public health problems worldwide. However, licensed DENV vaccine has restrictions on its use, and there is currently no approved ZIKV vaccine. Development of a potent and safe flavivirus vaccine is urgently needed. As a previous study revealed the epitope, RCPTQGE, located on the bc loop in the E protein domain II of DENV, in this study, we rationally designed and synthesized a series of peptides based on the sequence of JEV epitope RCPTTGE and DENV/ZIKV epitope RCPTQGE. METHODS: Immune sera were generated by immunization with the peptides which were synthesized by using five copies of RCPTTGE or RCPTQGE and named as JEV-NTE and DV/ZV-NTE. Immunogenicity and neutralizing abilities of JEV-NTE or DV/ZV-NTE-immune sera against flavivirus were evaluated by ELISA and neutralization tests, respectively. Protective efficacy in vivo were determined by passive transfer the immune sera into JEV-infected ICR or DENV- and ZIKV-challenged AG129 mice. In vitro and in vivo ADE assays were used to examine whether JEV-NTE or DV/ZV-NTE-immune sera would induce ADE. RESULTS: Passive immunization with JEV-NTE-immunized sera or DV/ZV-NTE-immunized sera could increase the survival rate or prolong the survival time in JEV-challenged ICR mice and reduce the viremia levels significantly in DENV- or ZIKV-infected AG129 mice. Furthermore, neither JEV -NTE- nor DV/ZV-NTE-immune sera induced antibody-dependent enhancement (ADE) as compared with the control mAb 4G2 both in vitro and in vivo. CONCLUSIONS: We showed for the first time that novel bc loop epitope RCPTQGE located on the amino acids 73 to 79 of DENV/ZIKV E protein could elicit cross-neutralizing antibodies and reduced the viremia level in DENV- and ZIKV-challenged AG129 mice. Our results highlighted that the bc loop epitope could be a promising target for flavivirus vaccine development.

The impact and outcomes of cancer-macrophage fusion.

BACKGROUND: Cancer's hallmark feature is its ability to evolve, leading to metastasis and recurrence. Although genetic mutations and epigenetic changes have been implicated, they don't fully explain the leukocytic traits that many cancers develop. Cell fusion between cancer and somatic cells, particularly macrophages, has been suggested as an alternative pathway for cancer cells to obtain new traits by acquiring exogenous genetic material. METHODS: This study aims to investigate the potential biological outcomes of tumor-myeloid cell fusion by generating tumor-macrophage hybrid cells. Two clones with markedly different tumorigenicity were selected, and RNA-seq was used to compare their RNA expressions with that of the control cells. Based on the results that the hybrid cells showed differential activation in several upstream regulator pathways that impact their biological behaviors, the hybrid cells' abilities to recruit stromal cells and establish angiogenesis as well as their cell cycle distributions were investigated through in vitro and in vivo studies. RESULTS: Although both hybrid clones demonstrated p53 activation and reduced growth rates, they exhibited distinct cell cycle distributions and ability to grow in vivo. Notably, while one clone was highly tumorigenic, the other showed little tumorigenicity. Despite these differences, both hybrid clones were potent environmental modifiers, exhibiting significant abilities to recruit stromal and immune cells and establish angiogenesis. CONCLUSIONS: The study revealed that tumor-somatic cell fusion is a potent environmental modifier that can modulate tumor survival and evolution, despite its relatively low occurrence. These findings suggest that tumor-somatic cell fusion could be a promising target for developing new cancer therapies. Furthermore, this study provides an experimental animal platform to investigate cancer-myeloid fusion and highlights the potential role of tumor-somatic cell fusion in modulating the tumor environment.

Optimization and Improvement of qPCR Detection Sensitivity of SARS-CoV-2 in Saliva.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a major public health threat globally, especially during the beginning of the pandemic in 2020. Reverse transcription-quantitative PCR (RT-qPCR) is utilized for viral RNA detection as part of control measures to limit the spread of COVID-19. Collecting nasopharyngeal swabs for RT-qPCR is a routine diagnostic method for COVID-19 in clinical settings, but its large-scale implementation is hindered by a shortage of trained health professionals. Despite concerns over its sensitivity, saliva has been suggested as a practical alternative sampling approach to the nasopharyngeal swab for viral RNA detection. In this study, we spiked saliva from healthy donors with inactivated SARS-CoV-2 from an international standard to evaluate the effect of saliva on viral RNA detection. On average, the saliva increased the cycle threshold (CT) values of the SARS-CoV-2 RNA samples by 2.64 compared to the viral RNA in viral transport medium. Despite substantial variation among different donors in the effect of saliva on RNA quantification, the outcome of the RT-qPCR diagnosis was largely unaffected for viral RNA samples with CT values of <35 (1.55 log10 IU/mL). The saliva-treated viral RNA remained stable for up to 6 h at room temperature and 24 h at 4°C. Further supplementing protease and RNase inhibitors improved the detection of viral RNA in the saliva samples. Our data provide practical information on the storage conditions of saliva samples and suggest optimized sampling procedures for SARS-CoV-2 diagnosis. IMPORTANCE The primary method for detection of SARS-CoV-2 is using nasopharyngeal swabs, but a shortage of trained health professionals has hindered its large-scale implementation. Saliva-based nucleic acid detection is a widely adopted alternative, due to its convenience and minimally invasive nature, but the detection limit and direct impact of saliva on viral RNA remain poorly understood. To address this gap in knowledge, we used a WHO international standard to evaluate the effect of saliva on SARS-CoV-2 RNA detection. We describe the detection profile of saliva-treated SARS-CoV-2 samples under different storage temperatures and incubation periods. We also found that adding protease and RNase inhibitors could improve viral RNA detection in saliva. Our research provides practical recommendations for the optimal storage conditions and sampling procedures for saliva-based testing, which can improve the efficiency of COVID-19 testing and enhance public health responses to the pandemic.

Longitudinal neutralizing antibody responses after SARS-CoV-2 infection: A convalescent cohort study in Taiwan.

BACKGROUND: Understanding the neutralizing antibody (NAb) titer against COVID-19 over time is important to provide information for vaccine implementation. The longitudinal NAb titer over one year after SARS-CoV-2 infection is still unclear. The purposes of this study are to evaluate the duration of the neutralizing NAb titers in COVID-19 convalescents and factors associated with the titer positive duration. METHODS: A cohort study followed COVID-19 individuals diagnosed between 2020 and 2021 May 15th from the COVID-19 database from the Taiwan Centers for Disease Control. We analyzed NAb titers from convalescent SARS-CoV-2 individuals. We used generalized estimating equations (GEE) and a Cox regression model to summarize the factors associated with NAb titers against COVID-19 decaying in the vaccine-free population. RESULTS: A total of 203 convalescent subjects with 297 analytic samples were followed for a period of up to 588 days. Our study suggests that convalescent COVID-19 in individuals after more than a year and four months pertains to only 25% of positive titers. The GEE model indicates that longer follow-up duration was associated with a significantly lower NAb titer. The Cox regression model indicated the disease severity with advanced condition was associated with maintaining NAb titers (adjusted hazard ratio: 2.01, 95% CI: 1.11-3.63) and that smoking was also associated with higher risk of negative NAb titers (adjusted hazard ratio: 0.55, 95% CI: 0.33-0.92). CONCLUSIONS: Neutralizing antibody titers diminished after more than a year. The antibody titer response against SARS-CoV-2 in naturally convalescent individuals provides a reference for vaccinations.

Hepatic-Modulatory Effects of Chicken Liver Hydrolysate-Based Supplement on Autophagy Regulation against Liver Fibrogenesis.

Chicken-liver hydrolysates (CLHs) have been characterized as performing several biofunctions by our team. This study aimed to investigate if a CLH-based supplement (GBHP01TM) can ameliorate liver fibrogenesis induced by thioacetamide (TAA) treatment. Our results showed that the TAA treatment caused lower body weight gains and enlarged livers, as well as higher serum ALT, AST, and ALP levels (p < 0.05). This liver inflammatory and fibrotic evidence was ameliorated (p < 0.05) by supplementing with GBHP01TM; this partially resulted from its antioxidant abilities, including decreased TBARS values but increased TEAC levels, reduced GSH contents and catalase/GPx activities in the livers of TAA-treated rats (p < 0.05). Additionally, fewer nodules were observed in the appearance of the livers of TAA-treated rats after supplementing with GBHP01TM. Similarly, supplementing GBHP01TM decreased fibrotic scars and the fibrotic score in the livers of TAA-treated rats (p < 0.05). Moreover, the increased hepatic IL-6, IL-1ß, and TNF-α levels after TAA treatment were also alleviated by supplementing with GBHP01TM (p < 0.05). Meanwhile, GBHP01TM could decrease the ratio of LC3B II/LC3B I, but upregulated P62 and Rab7 in the livers of TAA-treated rats (p < 0.05). Taking these results together, the CLH-based supplement (GBHP01TM) can be characterized as a natural agent against liver fibrogenesis.

Correction: Lee et al. The Synergistic Inhibition of Coronavirus Replication and Induced Cytokine Production by Ciclesonide and the Tylophorine-Based Compound Dbq33b. Pharmaceutics 2022, 14, 1511.

In the original publication [...].

Prophylactic Antibiotics for Deep Inferior Epigastric Perforator Flap Breast Reconstruction: A Comparison between Three Different Duration Approaches.

There is no consensus on the duration of prophylactic antibiotic use for autologous breast reconstruction after mastectomy. We attempted to standardize the use of prophylactic antibiotics after mastectomy using a deep inferior epigastric perforator flap for the breast reconstruction procedure. Methods: This retrospective case series included 108 patients who underwent immediate breast reconstruction with a deep inferior epigastric perforator flap at the Ditmanson Medical Foundation Chia-Yi Christian Hospital between 2012 and 2019. Patients were divided into three groups based on the duration of prophylactic antibiotic administration (1, 3, and >7 days) for patients with drains. Data were analyzed between January and April 2021. Results: The prevalence of surgical site infection in the breast was 0.93% (1/108), and in the abdomen it was 0%. The patient groups did not differ by age, body mass index, smoking status, or neoadjuvant chemotherapy. Only one patient experienced surgical site infection in the breast after half-deep necrosis of the inferior epigastric perforator flap. There were no significant differences in surgical site infection based on the duration of prophylactic antibiotic use. The operation time, methods of breast surgery, volume of fluid drainage in the first 3 days of the abdominal and breast drains, and day of removal of the abdominal and breast drains did not affect surgical site infection. Conclusion: Based on these data, we do not recommend extending prophylactic antibiotics beyond 24 hours in deep inferior epigastric perforator reconstruction.

Upregulation of PD-L1 by SARS-CoV-2 promotes immune evasion.

Patients with severe COVID-19 often suffer from lymphopenia, which is linked to T-cell sequestration, cytokine storm, and mortality. However, it remains largely unknown how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces lymphopenia. Here, we studied the transcriptomic profile and epigenomic alterations involved in cytokine production by SARS-CoV-2-infected cells. We adopted a reverse time-order gene coexpression network approach to analyze time-series RNA-sequencing data, revealing epigenetic modifications at the late stage of viral egress. Furthermore, we identified SARS-CoV-2-activated nuclear factor-κB (NF-κB) and interferon regulatory factor 1 (IRF1) pathways contributing to viral infection and COVID-19 severity through epigenetic analysis of H3K4me3 chromatin immunoprecipitation sequencing. Cross-referencing our transcriptomic and epigenomic data sets revealed that coupling NF-κB and IRF1 pathways mediate programmed death ligand-1 (PD-L1) immunosuppressive programs. Interestingly, we observed higher PD-L1 expression in Omicron-infected cells than SARS-CoV-2 infected cells. Blocking PD-L1 at an early stage of virally-infected AAV-hACE2 mice significantly recovered lymphocyte counts and lowered inflammatory cytokine levels. Our findings indicate that targeting the SARS-CoV-2-mediated NF-κB and IRF1-PD-L1 axis may represent an alternative strategy to reduce COVID-19 severity.