Seroreactivity against Leptospira spp. differs between community cats and privately-owned cats in Hong Kong.

Leptospirosis is a bacterial zoonotic disease of major One Health significance and public health impact globally, with a wide host range including mammals, cetaceans and herpetofauna. This study aimed to determine Leptospira seroprevalence, risk factors for seroreactivity and prevalence of urinary Leptospira shedding among domestic cats in Hong Kong. Microagglutination testing of 22 Leptospira serovars from 20 serogroups was performed on 738 sera from outdoor free-roaming "community" cats (n = 391) and privately-owned (n = 347) cats. Urine from 268 community cats was tested for pathogenic Leptospira DNA by qPCR targeting lipL32. Potential risk factors associated with exposure were assessed using logistic regression. Overall Leptospira seroprevalence was 9.35%. Of 14 serogroups detected, Javanica (4.3%), Djasiman (2.3%) and Australis (1.5%) were most common. Seroreactivity was significantly higher among community (13.3%) than privately-owned cats (4.9%; OR 2.98 [95% CI 1.68-5.25], P < 0.001), especially to Javanica (7.65% of community cats versus 0.58% of privately-owned cats (P < 0.001). Antibody titres to all serogroups ranged from 1:100 to 1:6400 (median 1:200) and were highest for Javanica (median 1:800). Leptospira DNA was detected in urine from 12/268 community cats (4.48%; median load 6.42 × 102 copies/mL urine; range 1.40 × 101-9.63 × 104). One in three seroreactive community cats with paired urine and blood samples had leptospiruria. After adjusting for source, none of breed, sex, neuter status, age, district rodent infestation rate, serum alanine transaminase or creatinine values were associated with seroreactivity. Cats in Hong Kong are exposed to a diversity of Leptospira serogroups and can shed Leptospira silently in urine. The higher seroprevalence among outdoor free-roaming community cats highlights the importance of environmental drivers in leptospirosis transmission and risks of exposure for sympatric human populations. Gloves should be worn when handling feline urine to minimise the risk of zoonotic transmission from subclinically infected cats.

Seroprevalence of B. pertussis infection and the changes of specific antibody levels in health care workers during the first two years of COVID-19 in Wuhu, China.

BACKGROUND: The reported number of pertussis cases declined after the implementation of COVID-19 prevention and control measures, however, the burden of pertussis among adults in China remains largely unknown. Additionally, the waning of natural antibody level has also rarely been assessed. METHODS: A total of 762 healthcare workers (HCWs) who had underwent the health examinations in 2021 and 2022 were included. Serum anti-PT IgG and IgA levels were determined by ELISA. Recent B. pertussis infection was defined as anti-PT IgG ≥100 IU/ml and/or anti-PT IgA ≥10 IU/ml. RESULTS: In 2021, the seroprevalence of recent B. pertussis infection was 10.1 %, and those HCWs in outpatient department had a higher percentage (18.6 %), and geometric mean concentration (GMC) (6.3 IU/ml) than those in other departments. This seroprevalence decreased to 2.4 % in 2022, although the difference remained significant. In the 77 subjects with recent B. pertussis infection in 2021, anti-PT IgG was undetectable in 18 cases the following year. Majority (68/76) of the subjects with anti-PT IgA ≥10 IU/ml in 2021 no longer had detected this antibody in 2022. Among 95 pertussis cases, approximately 60.0 % of cases reported no history of cough. Among those with a documented cough history, 36 cases with suspected pertussis courses who had never been diagnosed. Prolonged cough with nocturnal exacerbation (29/38) was the most commonly reported clinical symptom, and whoop was confirmed in six cases. Uroclepsia and syncopes during the cough attacks were reported by three and one subjects, respectively. One case presented with subconjunctival hemorrhage and tensionic purpura during the course. CONCLUSIONS: The results suggested a high prevalence of B. pertussis infection among HCWs. The presence of unrecognized adult pertussis cases and the rapid waning of antibody indicate the need to improve clinical management for suspected pertussis in adults, and to updated immunization schedule after childhood program.

Washed microbiota transplantation combined with biological agents promotes histological remission in refractory severe ulcerative colitis with recurrent intestinal infection: A case report.

Ulcerative colitis (UC) is a chronic non-specific colitis disease. In recent years, fecal microbiota transplantation (FMT), including improved washed microbiota transplantation (WMT), and biological agents have helped improve the prognosis of patients with UC. However, a significant number of patients with moderate to severe UC do not get relief from glucocorticoids, immunosuppressants, and TNF-α antagonists. Patients with severe UC are frequently burdened with opportunistic infections and subsequent surgical interventions. Combined treatment modalities are crucial for patients with severe UC and opportunistic infections. Herein, we reported a case of a 25-year-old female with refractory severe UC complicated with recurrent Clostridioides difficile infection and recurrent cytomegalovirus infection for six years. Surgical removal of the affected bowel segment was almost unavoidable. She showed endoscopic and histological recovery after comprehensive WMT and Vedolizumab treatment. The following are our learnings from the case: 1. A combination of WMT and biological agents can potentially obviate the necessity for surgical treatment in patients with refractory severe UC and promote histological remission. 2. Personalized comprehensive treatment and chronic disease management models for patients with UC should be emphasized. 3. WMT can help treat opportunistic infections, which may also strengthen the treatment with gut-targeted biological agents when traditional TNF-α antagonists show poor efficacy.

[Exploration of cancer biological characteristics in people with different five movements and six climates constitution based on pan-cancer Bulk RNA-Seq].

According to the theory of five movements and six climates, the innate constitution plays a crucial role in determining the underlyingpa thological mechanisms of diseases later in life. Previous studies have demonstrated a close association between the constitution, as defined by the theory of five movements and six climates, and the development of various types of tumors. Furt hermore,the tumorsubtype determined by the constitution has prognostic implications. This highlights the potential of utilizing the fivemovements and six climates theory to guide the implementation of precision medicine strategies in thefield of oncology. However, no resear ch has yet been conducted to investigate the use of this theory in guiding the development of tumor molecular classification and precisi onmedicine strategies. The objective of this research is to uncover the biological characteristics of each constitution within a pancanc ercohort and identify potential anti-tumor drugs that are applicable to patients with different constitutional types. By doing so, we aimto c ontribute to the establishment of a precision medicine strategy for tumors derived from the original concepts of traditional Chi nesemedicine(TCM). In this study, we obtainedpan-cancer Bulk RNA-Seq data from UCSC Xena, GWAS cohort data from the UKBiobank, and cis-eQTLs data from eQ TLGen and GTEx V8. We employed machine learning methods to screen for hub genes associated with each constitution. Subsequently, we utilized informatics tools to explore the biological characteristics of each constitut iondefined by the theory of five movements and six bioclimates. Further, potential anti-tumor drugs suitable for patients with differen tconstitutional types were identified through mendelian randomization, molecular docking, and drug-like prediction techniques. Withinthe pan-cancer cohort, significant differences were observed among different constitutions in terms of progression-free interval, biological f unctions, immune cell abundance, tumor drug sensitivity, and immunotherapy response. These findings suggest that the five movements and six climates theory can guide tumor molecular classification and the development of precision medicine strategies. Moreover,the biological characteristics inherent to each constitution partially shed light on the scientific implications of Chinese medicinetheories, offering a fresh perspective towards clinical cancer treatment. Through molecular docking and drug-like prediction, several po tential anti-tumor drugs such as 17-beta-estradiol, serotonin, trans-resveratrol, and linoleic acid were identified. Overall, the util izationof multi-omics approaches pro vides a powerful tool to unravel the scientific foundations of TCM theories. The elucidation of themu lti-omics features associated witheach constitution in tumors serves as the basis for applying the five movements and six climates theoryto tumor molecular classification and the development of precision medicine strategies.

Temporally resolved proteomics identifies nidogen-2 as a cotarget in pancreatic cancer that modulates fibrosis and therapy response.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by increasing fibrosis, which can enhance tumor progression and spread. Here, we undertook an unbiased temporal assessment of the matrisome of the highly metastatic KPC (Pdx1-Cre, LSL-KrasG12D/+, LSL-Trp53R172H/+) and poorly metastatic KPflC (Pdx1-Cre, LSL-KrasG12D/+, Trp53fl/+) genetically engineered mouse models of pancreatic cancer using mass spectrometry proteomics. Our assessment at early-, mid-, and late-stage disease reveals an increased abundance of nidogen-2 (NID2) in the KPC model compared to KPflC, with further validation showing that NID2 is primarily expressed by cancer-associated fibroblasts (CAFs). Using biomechanical assessments, second harmonic generation imaging, and birefringence analysis, we show that NID2 reduction by CRISPR interference (CRISPRi) in CAFs reduces stiffness and matrix remodeling in three-dimensional models, leading to impaired cancer cell invasion. Intravital imaging revealed improved vascular patency in live NID2-depleted tumors, with enhanced response to gemcitabine/Abraxane. In orthotopic models, NID2 CRISPRi tumors had less liver metastasis and increased survival, highlighting NID2 as a potential PDAC cotarget.

COVID-19 Vaccination Reporting and Adverse Event Analysis in Taiwan.

The COVID-19 pandemic necessitated an urgent global response in vaccine deployment, achieving over 70.6% global vaccination coverage with at least one dose. This study focuses on Taiwan's vaccine administration and adverse event reporting, set against a global backdrop. Using data from Taiwan's Vaccine Adverse Event Reporting System (VAERS) and global vaccination data, this study investigates vaccine safety and the public health implications of vaccination strategies from local and global perspectives. Taiwan's proactive approach, resulting in high vaccination rates, provides a case study for the monitoring and management of vaccine-related adverse events. This study offers insights into the safety profiles of various COVID-19 vaccines and further explores the implications of adverse event reporting rates for vaccine policy and public health strategies. The comparative analysis reveals that, while vaccination has been effective in controlling the virus's spread, safety monitoring remains critical for maintaining public trust. It underscores the necessity of enhanced surveillance and the importance of transparent and tailored risk communication to support informed public health decisions. The findings aim to contribute to the global dialogue on vaccine safety, equitable distribution, evidence-based policy-making, and development of mitigation measures with consideration of local demographics in the ongoing fight against COVID-19.

[Determination of nine components of fried Ziziphi Spinosae Semen extract in beagle dog plasma by UPLC-MS/MS and its application in pharmacokinetic research].

This study established a convenient, rapid, and sensitive ultra-performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS) method for simultaneous determination of magnoflorine,(R)-coclaurine, vicenin Ⅱ, isospinosin, spinosin, swertisin, N-nornuciferine, 6-feruloylspinosin, and jujuboside B in beagle dog plasma after oral administration of fried Ziziphi Spinosae Semen(FZSS) extract. The Waters HSS-T3 C_(18) column(2.1 mm×100 mm, 1.8 µm) was used. The methanol-aqueous solution(containing 0.01% formic acid) was adopted as the mobile phase for gradient elution. The nine components and two internal standards were completely separated within 8 min. The mass spectrometry detection was performed in multiple reaction monitoring(MRM) mode by positive and negative ion switching of electrospray ionization. The analytical method was validated in terms of specificity, selectivity, linear range, accuracy, precision, recovery, matrix effect, and stability. It could meet the requirement of pharmacokinetic research after oral administration of FZSS extract to beagle dogs. The results showed that the time to reach the peak concentration(T_(max)) of magnoflorine,(R)-coclaurine, vicenin Ⅱ, isospinosin, spinosin, 6-feruloylspinosin, and jujuboside B was 2.40-3.20 h, and the elimination halflife(t_(1/2)) was 2.08-6.79 h after a single-dose oral administration of FZSS to beagle dogs. The exposure of magnoflorine and spinosin was high, with a peak concentration(C_(max)) of 76.7 and 31.5 ng·mL~(-1) and an area under the curve(AUC_(0-∞)) of 581 and 315 ng·h·mL~(-1), respectively. The exposure of the remaining five compounds was lower, with a C_(max) of 0.81-13.0 ng·mL~(-1) and an AUC_(0-∞) of 6.00-106 ng·h·mL~(-1). This study provides a reference for the follow-up research of FZSS.

Measuring disease burden of dominant variants of COVID-19 in Taiwan.

Objectives: The disability-adjusted life years (DALYs) of COVID-19 have been applied as a time-based measurement to estimate years of life lost due to premature mortality or healthy life lost in different countries. Limited information was found for DALYs among different variants of concern (VOC). Methods: Disease severities based on categories of asymptomatic, mild, moderate, severe, and critical cases were explored among different VOC by analyzing the proportions in confirmed cases. DALY or years of healthy life lost due to disability (YLD)-based annual burdens of COVID-19 on different ages, genders as well as trend analysis were also evaluated for VOC in Taiwan. Results: Different trends were observed in years of life lost due to premature mortality (YLLs) or YLD for various age or gender categories. Disease severity at critical stage had the highest percentage for overall YLDs encompassed from 2020 to 2022. Also, critical-grade cases were found to be predominantly caused by Wild-type, Alpha, and Omicron variants in 2020, 2021, and 2022, respectively. Conclusion: Precautionary measures are also suggested for policy makers to take in specific seasons, age or gender groups based on YLL and YLD analyses.

Seroprevalence of tetanus and pertussis antibodies among health care workers in Wuhu, China.

This study aimed to elucidate the seroprevalence of antibodies to tetanus and pertussis among Chinese health care workers. Blood specimens from health care workers were collected during the 2021 annual medical examination at the First People's Hospital of Wuhu. Commercial ELISA kits were employed to quantify serum IgG antibodies against tetanus toxin (anti-TT IgG) and both IgG and IgA antibodies against pertussis toxin (anti-PT IgG, anti-PT IgA). A concentration of anti-TT IgG exceeding 0.1 IU/ml was deemed seroprotective against tetanus, while concentrations of anti-PT IgG ≥ 50 IU/ml or anti-PT IgA ≥ 15 IU/ml were indicative of a prior pertussis infection. The overall seroprotective rate for anti-TT IgG stood at 10.43% (92/882), with the highest seroprotective rate (13.91%) in the 20-29 age group, followed by the 30-39 age group (10.57%), 40-49 age group (5.80%), and 50-59 age group (5.63%). Eighteen (2.04%) of the studied subjects were positive to anti-PT IgG, and the positive rate in 20-39 age group and 40-59 age group was 1.19% (8/673) and 4.78% (10/209), respectively. Thirty (3.40%) subjects displayed anti-PT IgG levels ≥100 IU/ml and/or anti-PT IgA ≥ 15 IU/ml, suggesting a recent pertussis infection within the preceding year. Over half (503/882, 57.03%) had undetectable anti-PT IgG antibodies. The majority of health care workers in China appear susceptible to tetanus and pertussis, and a significant subset has experienced pertussis infection. The implementation of booster vaccinations against these diseases for Chinese health care workers is recommended.

A Security Information Transmission Method Based on DHR for Seafloor Observation Network.

A seafloor observation network (SON) consists of a large number of heterogeneous devices that monitor the deep sea and communicate with onshore data centers. Due to the long-distance information transmission and the risk of malicious attacks, ensuring the integrity of data in transit is essential. A cryptographically secure frame check sequence (FCS) has shown great advantages in protecting data integrity. However, the commonly used FCS has a collision possibility, which poses a security risk; furthermore, reducing the encryption calculation cost is a challenge. In this paper, we propose a secure, lightweight encryption scheme for transmitted data inspired by mimic defense from dynamic heterogeneous redundancy theory. Specifically, we use dynamic keys to encrypt a data block and generate multiple encrypted heterogeneous blocks for transmission. These continuously changing encrypted data blocks increase the confusion regarding the original encoded data, making it challenging for attackers to interpret and modify the data blocks. Additionally, the redundant information from the multiple blocks can identify and recover tampered data. Our proposed scheme is suitable for resource-constrained environments where lightweight encryption is crucial. Through experimental demonstrations and analysis methods, we determine the effectiveness of our encryption scheme in reducing computational costs and improving security performance to protect data integrity.

Degeneration of the Olfactory System in a Murid Rodent that Evolved Diurnalism.

In mammalian research, it has been debated what can initiate an evolutionary tradeoff between different senses, and the phenomenon of sensory tradeoff in rodents, the most abundant mammalian clade, is not evident. The Nile rat (Arvicanthis niloticus), a murid rodent, recently adapted to a diurnal niche through an evolutionary acquisition of daylight vision with enhanced visual acuity. As such, this model provides an opportunity for a cross-species investigation where comparative morphological and multi-omic analyses of the Nile rat are made with its closely related nocturnal species, e.g. the mouse (Mus musculus) and the rat (Rattus norvegicus). Thus, morphological examinations were performed, and evolutionary reductions in relative sizes of turbinal bone surfaces, the cribriform plate, and the olfactory bulb were discovered in Nile rats. Subsequently, we compared multiple murid genomes, and profiled olfactory epithelium transcriptomes of mice and Nile rats at various ages with RNA sequencing. The results further demonstrate that, in comparison with mouse olfactory receptor (OR) genes, Nile rat OR genes have experienced less frequent gain, more frequent loss, and more frequent expression reduction during their evolution. Furthermore, functional degeneration of coding sequences in the Nile rat lineage was found in OR genes, yet not in other genes. Taken together, these results suggest that acquisition of improved vision in the Nile rat has been accompanied by degeneration of both olfaction-related anatomical structures and OR gene repertoires, consistent with the hypothesis of an olfaction-vision tradeoff initiated by the switch from a nocturnal to a diurnal lifestyle in mammals.

Sertraline-Induced Acute Pancreatitis: A Case Report and Literature Review.

Objective: Acute pancreatitis (AP) is a process of acute inflammation and cell damage of the pancreas. Gallstones and alcohol abuse are the most common cause for AP. Drug-induced pancreatitis (DIP), accounting for less than 3% of the AP, has become increasingly recognized as an additional and vitally important etiology of acute pancreatitis. Sertraline is an antidepressant of the selective serotonin reuptake inhibitor (SSRI)class that has a range of side effects even when used at the recommended dose. A recognized but rare association in teenagers is acute pancreatitis. The report is of a 15-year-old male teenager with a history of depression who developed acute pancreatitis following self-overdose of his sertraline prescription. Case Report: A 15-year-old teenager with an overdose of sertraline, which was the only medication he took, presented abdominal pain, nausea, and vomiting. The common causes of alcohol consumption, gallstones, biliary duct obstruction, malignancy, trauma, hypertriglyceridemia, and hypercalcemia were eliminated. The increased level of amylase and parenchymal edema of the pancreas revealed in computed tomography supported the diagnosis of acute pancreatitis. After discontinuation of the drug and conventional acute pancreatitis treatment, he recovered evenly. Conclusion: With the increasing use of antidepressant medications in patients of teenagers, this report is a reminder that clinicians should be aware of the association between SSRIs such as sertraline, particularly in cases of overdose, and the development of acute pancreatitis.

Glycerol kinase enzyme is a prognostic predictor in esophageal carcinoma and is associated with immune cell infiltration.

The influence of lipid metabolism on tumorigenesis and progression has garnered significant attention. However, the role of Glycerol Kinase (GK), a key enzyme in glycerol metabolism, in Esophageal Carcinoma (ESCA) remains unclear. To further elucidate the relationship between GK and ESCA, we investigated GK expression levels using database information. Controlled studies employing immunohistochemistry were conducted on clinical ESCA tumor samples and normal specimens, confirming GK's elevated expression in ESCA. Analysis of The Cancer Genome Atlas (TCGA) data via Kaplan-Meier (KM) survival plots revealed that increased GK expression correlates with poorer ESCA patient outcomes, particularly in overall survival (OS) and disease-specific survival (DSS). Multiple regression analysis indicated that elevated GK expression is an independent risk factor affecting ESCA prognosis. Statistical analysis of prognostic data from clinical samples further corroborated this finding. Moreover, there appears to be a significant correlation between GK expression and immune infiltration, specifically involving certain T and B lymphocytes. In conclusion, elevated GK expression in ESCA is strongly linked to poor prognosis and increased immune cell infiltration, highlighting its potential as an independent prognostic biomarker and a viable therapeutic target.

One-Electron (2c/1e) Tin···Tin Bond Stabilized by ortho-Phenylenediamido Ligands.

Odd-electron bonds, i.e., the two-center, three-electron (2c/3e), or one-electron (2c/1e) bonds, have attracted tremendous interest owing to their novel bonding nature and radical properties. Herein, complex [K(THF)6][LSn:···Sn:L] (1), featuring the first and unsupported 2c/1e Sn···Sn σ-bond with a long distance (3.2155(9) Å), was synthesized by reduction of stannylene [LSn:] (L = N,N-dpp-o-phenylene diamide) with KC8. The one-electron Sn-Sn bond in 1 was confirmed by the crystal structure, DFT calculations, EPR spectroscopy, and reactivity studies. This compound can be viewed as a stabilized radical by delocalizing to two metal centers and can readily mediate radical reactions such as C-C coupling of benzaldehyde.

Neutrophil-lymphocyte ratio reflects tumour-infiltrating lymphocytes and tumour-associated macrophages and independently predicts poor outcome in breast cancers with neoadjuvant chemotherapy.

AIMS: The neutrophil-lymphocyte ratio (NLR) is a systemic reflection of cancer-associated inflammation and a prognostic marker for breast cancer. For the local tumour microenvironment, tumour-infiltrating lymphocytes (TILs) and tumour-associated macrophages (TAMs) are also highly correlated with breast cancer survival. This study aimed to explore the relationship between the circulating and local immune microenvironment, and to further delineate the prognostic role of NLR in breast cancer patients receiving neoadjuvant chemotherapy (NAC). METHODS: A cohort of breast cancer patients receiving NAC with subsequent surgery was retrieved. Clinical data were reviewed. Histological slides and CD8 immunohistochemistry from biopsy (pre-chemotherapy) and excision (postchemotherapy) specimens were assessed for TILs and TAMs. RESULTS: A total of 146 patients were included. There was a significant positive correlation between pre- and postsurgery NLR at a cut-off of 2.6 (median pre-chemotherapy NLR) (P < 0.001). NLR pre-chemotherapy was associated positively with necrosis on biopsy (P = 0.027) and excision (P = 0.021) and TAMs on excision (P = 0.049). NLR 1 year postsurgery was associated with high tumour stage (P = 0.050) and low histological grade (P = 0.008). TIL count was lower in NLR-high cases at almost all time-points by histological assessment and CD8 immunostaining (P < 0.050). In multivariate analysis, postsurgery NLR is an independent predictor for overall survival [OS; hazard ratio (HR) = 9.524, P < 0.001], breast cancer-specific survival (BCSS) (HR = 10.059, P = 0.001) and disease-free survival (DFS; HR = 2.824, P = 0.016). CONCLUSIONS: The association between NLR with tumour necrosis, TAMs and TILs illustrates an interaction between the circulating and local immune microenvironment. Late NLR is a strong indicator of outcome and may be useful for prognostication and disease monitoring.

Pharmacokinetics and safety evaluation of intravenously administered Pseudomonas phage PA_LZ7 in a mouse model.

IMPORTANCE: Phage therapy is gaining traction as an alternative to antibiotics due to the rise of multi-drug-resistant (MDR) bacteria. This study assessed the pharmacokinetics and safety of PA_LZ7, a phage targeting MDR Pseudomonas aeruginosa, in mice. After intravenous administration, the phage showed an exponential decay in plasma and its concentration dropped significantly within 24 h for all dosage groups. Although there was a temporary increase in certain plasma cytokines and spleen weight at higher dosages, no significant toxicity was observed. Therefore, PA_LZ7 shows potential as an effective and safe candidate for future phage therapy against MDR P. aeruginosa infections.

Isolation and identification of vapA-absent Aeromonas salmonicida in diseased snakehead Channa argus in China.

Aeromonas salmonicida is the typical pathogen causing furunculosis, reported widely in salmonids. Because of multiple serotypes, the control of A. salmonicida-caused disease has increasingly received much attention. Recently, A. salmonicida infection was reported in non-salmonid fish species. Here, a pathogenic A. salmonicida, named as As-s, was isolated from cultured snakehead (Channa argus) in a local fish farm in Shandong, China. As-s displayed clear hemolysis, amylase, and positive catalase activities, and grew at a wide range of temperatures (10-37 °C) and pH values (5.5-8.5). As-s was highly sensitive to cefuroxime sodium, ceftriaxone, ceftazidime, piperacillin, and cefoperazone and also apparently sensitive to chloramphenicol, erythromycin, and 25% cinnamaldehyde. The Virulence array protein gene cloning' results suggested that As-s has this gene compared with the other two vapA-containing strains, despite a close relationship of these strains via phylogenetic analysis. Severe ulcers on skin, muscle, and abnormal liver, and hemorrhage in pectoral/ventral fins and anal region were observed, and exophthalmos were also noticed in infected juvenile snakehead, as well as necrosis and infiltration of blood cells emerged in the internal organs using pathological section. In addition, As-s caused high mortality in snakehead, consistently with its immune gene response. This study reports the first isolation of vapA-absent A. salmonicida in snakehead.

Pharmacogenomic Landscape of Ivermectin and Selective Antioxidants: Exploring Gene Interplay in the Context of Long COVID.

COVID-19 pandemic has caused widespread panic and fear among the global population. As such, repurposing drugs are being used as viable therapeutic options due to the limited effective treatments for Long COVID symptoms. Ivermectin is one of the emerging repurposed drugs that has been shown effective to have antiviral effects in clinical trials. In addition, antioxidant compounds are also gaining attention due to their capabilities of reducing inflammation and severity of symptoms. Due to the absence of knowledge in pharmacogenomics and modes of actions in the human body for these compounds, this study aims to provide a pharmacogenomic profile for the combination of ivermectin and six selected antioxidants (epigallocatechin gallate (EGCG), curcumin, sesamin, anthocyanins, quercetin, and N-acetylcysteine (NAC)) as potentially effective regimens for long COVID symptoms. Results showed that there were 12 interacting genes found among the ivermectin, 6 antioxidants, and COVID-19. For network pharmacology, the 12 common interacting genes/proteins had the highest associations with Pertussis pathway, AGE-RAGE signaling pathway in diabetic complications, and colorectal cancer in the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Disease analyses also revealed that the top three relevant diseases with COVID-19 infections were diabetes mellitus, ischemia, reperfusion injury. We also identified 6 potential target microRNAs (miRNAs) of the 12 commonly curated genes used as molecular biomarkers for COVID-19 treatments. The established pharmacogenomic network, disease analyses, and identified miRNAs could facilitate developments of effective regimens for chronic sequelae of COVID-19 especially in this post-pandemic era. However, further studies and clinical trials are needed to substantiate the effectiveness and dosages for COVID-19 treatments.

Engineered phage with cell-penetrating peptides for intracellular bacterial infections.

IMPORTANCE: Salmonella infection is a significant threat to global public health, and the increasing prevalence of antibiotic resistance exacerbates the situation. Therefore, finding new and effective ways to combat this pathogen is essential. Phages are natural predators of bacteria and can be used as an alternative to antibiotics to kill specific bacteria, including drug-resistant strains. One significant limitation of using phages as antimicrobial agents is their low cellular uptake, which limits their effectiveness against intracellular bacterial infections. Therefore, finding ways to enhance phage uptake is crucial. Our study provides a straightforward strategy for displaying cell-penetrating peptides on non-model phages, offering a promising novel and effective therapeutic approach for treating intracellular and drug-resistant bacteria. This approach has the potential to address the global challenge of antibiotic resistance and improve public health outcomes.