A multicenter, double-blind, randomized, parallel-group, active-controlled, phase 3 clinical trial to compare the effectiveness and safety of two botulinum toxin type A formulations for improving moderate to severe glabellar wrinkles in Asians.

Botulinum toxin type A (BoNT-A) was first isolated in 1946, and since then, several formulations have been developed and widely used to treat wrinkles by inducing muscle paralysis. This multicenter, double-blind, randomized, parallel-group, active-controlled phase 3 clinical trial was designed to evaluate the efficacy and safety of a newly developed BoNT-A formulation, BMI2006, in improving moderate to severe glabellar wrinkles and to compare with existing onabotulinumtoxin A (OBoNT) injections. A total of 276 subjects were enrolled and received 20 units of the randomized material, which was intramuscularly injected into five different locations on the forehead. The primary endpoint, assessed at 4 weeks, showed no statistically significant difference in the improvement rate of glabellar wrinkles between the two groups, with BMI2006 demonstrating non-inferiority to comparator BoNT-A. Secondary endpoints, evaluated by both treating investigators and independent investigators, also exhibited similar improvement rates throughout the study period. Both groups reported high levels of satisfaction with no statistical difference between the two groups. Safety evaluations indicated mild and transient adverse events, with no serious reactions observed. In conclusion, BMI2006 is an effective and safe BoNT-A for treating glabellar wrinkles with an expected duration of action between 8 and 12 weeks.

Energy­stress­mediated activation of AMPK sensitizes MPS1 kinase inhibition in triple­negative breast cancer.

Monopolar spindle 1 kinase (Mps1, also known as TTK protein kinase) inhibitors exert marked anticancer effects against triple­negative breast cancer (TNBC) by causing genomic instability and cell death. As aneuploid cells are vulnerable to compounds that induce energy stress through adenosine monophosphate­activated protein kinase (AMPK) activation, the synergistic effect of Mps1/TTK inhibition and AMPK activation was investigated in the present study. The combined effects of CFI­402257, an Mps1/TTK inhibitor, and AICAR, an AMPK agonist, were evaluated in terms of cytotoxicity, cell­cycle distribution, and in vivo xenograft models. Additional molecular mechanistic studies were conducted to elucidate the mechanisms underlying apoptosis and autophagic cell death. The combination of CFI­402257 and AICAR showed selective cytotoxicity in a TNBC cell line. The formation of polyploid cells was attenuated, and apoptosis was increased by the combination treatment, which also induced autophagy through dual inhibition of the PI3K/Akt/mTOR and mitogen­activated protein kinase (MAPK) signaling pathways. Additionally, the combination therapy showed strongly improved efficacy in comparison with CFI­402257 and AICAR monotherapy in the MDA­MB­231 xenograft model. The present study suggested that the combination of CFI­402257 and AICAR is a promising therapeutic strategy for TNBC.

Pilot study indicates that a gluten-free diet lowers oxidative stress for gluten-sensitive persons with schizophrenia.

One-third of people with schizophrenia have elevated levels of anti-gliadin antibodies (AGA IgG). A 5-week randomized double-blind pilot study was performed in 2014-2017 in an inpatient setting to test the effect of a gluten-free diet (GFD) on participants with schizophrenia or schizoaffective disorder who also had elevated AGA IgG (≥ 20 U) but were negative for celiac disease. This earlier pilot study reported that the GFD-group showed improved gastrointestinal and psychiatric symptoms, and also improvements in TNF-α and the inflammatory cytokine IL-23. Here, we performed measurements of these banked plasma samples to detect levels of oxidative stress (OxSt) using a recently developed iridium (Ir)-reducing capacity assay. Triplicate measurements of these samples showed an Intraclass Correlation Coefficient of 0.84 which indicates good reproducibility. Further, a comparison of the OxSt measurements at the baseline and 5-week end-point for this small sample size shows that the GFD-group (N = 7) had lowered OxSt levels compared to the gluten-containing diet group (GCD; N = 9; p = 0.05). Finally, we showed that improvements in OxSt over these 5 weeks were correlated to improvements in gastrointestinal (r = +0.64, p = 0.0073) and psychiatric (r = +0.52, p = 0.039) symptoms. Also, we showed a possible association between the decrease in OxSt and the lowered levels of IL-23 (r = +0.44, p = 0.087), although without statistical significance. Thus, the Ir-reducing capacity assay provides a simple, objective measure of OxSt with the results providing further evidence that inflammation, redox dysregulation and OxSt may mediate interactions between the gut and brain.

Phf7 has impacts on the body growth and bone remodeling by regulating testicular hormones in male mice.

PHD finger protein 7 (Phf7) is a member of the PHF family proteins, which plays important roles in spermiogenesis. Phf7 is expressed in the adult testes and its deficiency causes male infertility. In this study, we tried to find the causal relationship between Phf7 deficiency and reduced growth retardation which were found in null knock-out (Phf7-/-) mice. Phf7-/- mice were born normally in the Mendelian ratio. However, the Phf7-/- males showed decreased body weight gain, bone mineral density, and bone mineral content compared to those in wild-type (WT) mice. Histological analysis for tibia revealed increased number of osteoclast cells in Phf7-/- mice compared with that in WT mice. When we analyzed the expressions for marker genes for the initial stage of osteoclastogenesis, such as receptor activator of nuclear factor kappa B (Rank) in tibia, there was no difference in the mRNA levels between Phf7-/- and WT mice. However, the expression of tartrate-resistant acid phosphatase (Trap), a mature stage marker gene, was significantly higher in Phf7-/- mice than in WT mice. In addition, the levels of testosterone and dihydrotestosterone (DHT), more potent and active form of testosterone, were significantly reduced in the testes of Phf7-/- mice compared to those in WT mice. Furthermore, testicular mRNA levels for steroidogenesis marker genes, namely Star, Cyp11a1, Cyp17a1 and 17ß-hsd, were significantly lower in Phf7-/- mice than in WT mice. In conclusion, these results suggest that Phf7 deficiency reduces the production of male sex hormones and thereby impairs associated bone remodeling.

Engineering TALE-linked deaminases to facilitate precision adenine base editing in mitochondrial DNA.

DddA-derived cytosine base editors (DdCBEs) and transcription activator-like effector (TALE)-linked deaminases (TALEDs) catalyze targeted base editing of mitochondrial DNA (mtDNA) in eukaryotic cells, a method useful for modeling of mitochondrial genetic disorders and developing novel therapeutic modalities. Here, we report that A-to-G-editing TALEDs but not C-to-T-editing DdCBEs induce tens of thousands of transcriptome-wide off-target edits in human cells. To avoid these unwanted RNA edits, we engineered the substrate-binding site in TadA8e, the deoxy-adenine deaminase in TALEDs, and created TALED variants with fine-tuned deaminase activity. Our engineered TALED variants not only reduced RNA off-target edits by >99% but also minimized off-target mtDNA mutations and bystander edits at a target site. Unlike wild-type versions, our TALED variants were not cytotoxic and did not cause developmental arrest of mouse embryos. As a result, we obtained mice with pathogenic mtDNA mutations, associated with Leigh syndrome, which showed reduced heart rates.

Sustaining essential health services in Lao PDR in the context of donor transition and COVID-19.

Lao People's Democratic Republic (Lao PDR) aims at graduating from least developed country status by 2026 and must increase the level of domestic financing for health. This paper examines how the government has prepared for the decline of external assistance and how donors have applied their transition approaches. Adapting a World Health Organization (WHO) framework, reflections and lessons were generated based on literature review, informal and formal consultations and focus group discussions with the Lao PDR government and development partners including budget impact discussion. The government has taken three approaches to transition from external to domestic funding: mobilizing domestic resources, increasing efficiency across programs and prioritization with a focus on strengthening primary health care (PHC). The government has increased gradually domestic government health expenditures as a share of the government expenditure from 2.6% in 2013 to 4.9% in 2019. The Ministry of Health has made efforts to design and roll out integrated service delivery of maternal, newborn, child, and adolescent health services, immunization and nutrition; integrated 13 information systems of key health programs into one single District Health Information Software 2; and prioritized PHC, which has led to shifting donors towards supporting PHC. Donors have revisited their aid policies designed to improve sustainability and ownership of the government. However, the government faces challenges in improving cross-programmatic efficiency at the operational level and in further increasing the health budget due to the economic crisis aggravated during Coronavirus disease 2019 (COVID-19). Working to implement donor transition strategies under the current economic situation and country challenges, calls into question the criteria used to evaluate transition. This criterion needs to include more appropriate indicators other than gross national income per capita, which does not reflect a country's readiness and capacity of the health system. There should be a more country-tailored strategy and support for considering the context and system-wide readiness during donor transition.

Redox-enabled electronic interrogation and feedback control of hierarchical and networked biological systems.

Microelectronic devices can directly communicate with biology, as electronic information can be transmitted via redox reactions within biological systems. By engineering biology's native redox networks, we enable electronic interrogation and control of biological systems at several hierarchical levels: proteins, cells, and cell consortia. First, electro-biofabrication facilitates on-device biological component assembly. Then, electrode-actuated redox data transmission and redox-linked synthetic biology allows programming of enzyme activity and closed-loop electrogenetic control of cellular function. Specifically, horseradish peroxidase is assembled onto interdigitated electrodes where electrode-generated hydrogen peroxide controls its activity. E. coli's stress response regulon, oxyRS, is rewired to enable algorithm-based feedback control of gene expression, including an eCRISPR module that switches cell-cell quorum sensing communication from one autoinducer to another-creating an electronically controlled 'bilingual' cell. Then, these disparate redox-guided devices are wirelessly connected, enabling real-time communication and user-based control. We suggest these methodologies will help us to better understand and develop sophisticated control for biology.

Hydrogen-Bonded Organic Framework-Polyoxometalate-Based System for Electrochromic Devices.

A porous hydrogen-bonded organic framework (HOF) structure was explored for the first time in the design of high-performance electrochromic devices (ECDs) using polyoxometalate (POM)-based charge-balancing layers as counter electrodes (CEs). The novelty of this work lies in the facile construction of films using small molecule-based EC materials to form a porous HOF structure. A full-cell model of an ECD was constructed by utilizing a POM-based CE to optimize the voltage distribution on the HOF-coated working electrode (WE). The addition of PW12O403- (PW12) on CE significantly enhanced the voltage distribution on EC electrodes and decreased the overvoltage on the WE, further preventing the formation of non-EC species and resulting in a 3.3-fold increase in the lifetime of the ECD. The optical contrast was enhanced from 47% (TiO2 only) to 68%, and the coloration efficiency was enhanced from 185 (TiO2 only) to 373 cm2 C-1. The optimized voltage distribution on the WE, leading to the fast response time and high optical EC contrast, could be explained by the charge-balancing effect. Overall, this new finding provides a robust framework for designing high-performance ECDs, taking advantage of the porous morphology and potential matching of the HOF and PW12.

HMBA ameliorates obesity by MYH9- and ACTG1-dependent regulation of hypothalamic neuropeptides.

The global epidemic of obesity remains a daunting problem. Here, we report hexamethylene bisacetamide (HMBA) as a potent anti-obesity compound. Peripheral and central administration of HMBA to diet-induced obese mice regulated the expression of hypothalamic neuropeptides critical for energy balance, leading to beneficial metabolic effects such as anorexia and weight loss. We found that HMBA bound to MYH9 and ACTG1, which were required for the anti-obesity effects of HMBA in both NPY-expressing and POMC-expressing neurons. The binding of HMBA to MYH9 and ACTG1 elevated the expression of HEXIM1 and enhanced its interaction with MDM2, resulting in the dissociation of the HEXIM1-p53 complex in hypothalamic cells. Subsequently, the free HEXIM1 and p53 translocated to the nucleus, where they downregulated the transcription of orexigenic NPY, but p53 and acetylated histone 3 upregulated that of anorexigenic POMC. Our study points to a previously unappreciated efficacy of HMBA and reveals its mechanism of action in metabolic regulation, which may propose HMBA as a potential therapeutic strategy for obesity.

The Development of a Permanent Implantable Spacer with the Function of Size Adjustability for Customized Treatment of Regurgitant Heart Valve Disease.

The Pivot Mandu is an innovative device featuring a leak-tight adjustable 3D balloon spacer, incorporating inner mesh support, an outer e-PTFE layer, and a compliant balloon in the middle layer with a specialized detachable system. To assess its feasibility, proof of concept was rigorously evaluated through bench testing and survival porcine animal experiments. The results demonstrated successful remote inflation of the balloon system, with the balloon spacer exhibiting sustained patent and functional integrity over an extended observation period of up to 6 months. A noteworthy feature of the newly designed 3D balloon spacer is its capability for easy size adjustment during procedures, enhancing its adaptability and practicality in clinical settings. This three-layered 3D balloon spacer, with its established long-term patency, exhibits highly encouraging outcomes that hold promise in overcoming the current limitations of spacer devices for heart valve diseases. Given the compelling results from preclinical investigations, the translation of the Pivot Mandu into human trials is strongly warranted.

Estimating the delivery costs of COVID-19 vaccination using the COVID-19 Vaccine Introduction and deployment Costing (CVIC) tool: the Lao People's Democratic Republic experience.

BACKGROUND: The COVID-19 Vaccine Introduction and deployment Costing (CVIC) tool was developed to assist countries to estimate incremental financial costs to roll out COVID-19 vaccines. This article describes the purposes, assumptions and methods used in the CVIC tool and presents the estimated financial costs of delivering COVID-19 vaccines in the Lao People's Democratic Republic (Lao PDR). METHODS: From March to September 2021, a multidisciplinary team in Lao PDR was involved in the costing exercise of the National Deployment and Vaccination Plan for COVID-19 vaccines to develop potential scenarios and gather inputs using the CVIC tool. Financial costs of introducing COVID-19 vaccines for 3 years from 2021 to 2023 were projected from the government perspective. All costs were collected in 2021 Lao Kip and presented in United States dollar. RESULTS: From 2021 to 2023, the financial cost required to vaccinate all adults in Lao PDR with primary series of COVID-19 vaccines (1 dose for Ad26.COV2.S (recombinant) vaccine and 2 doses for the other vaccine products) is estimated to be US$6.44 million (excluding vaccine costs) and additionally US$1.44 million and US$1.62 million to include teenagers and children, respectively. These translate to financial costs of US$0.79-0.81 per dose, which decrease to US$0.6 when two boosters are introduced to the population. Capital and operational cold-chain costs contributed 15-34% and 15-24% of the total costs in all scenarios, respectively. 17-26% went to data management, monitoring and evaluation, and oversight, and 13-22% to vaccine delivery. CONCLUSIONS: With the CVIC tool, costs of five scenarios were estimated with different target population and booster dose use. These facilitated Lao PDR to refine their strategic planning for COVID-19 vaccine rollout and to decide on the level of external resources needed to mobilize and support outreach services. The results may further inform inputs in cost-effectiveness or cost-benefit analyses and potentially be applied and adjusted in similar low- and middle-income settings.

Erector spinae plane block in laparoscopic colorectal surgery for reducing opioid requirement and facilitating early ambulation: a double-blind, randomized trial.

Various techniques have been formulated to reduce pain and ensure early recovery after surgery, as these are major concerns among surgeons, anesthesiologists, and patients. Erector spinae plane block (ESPB), the injection of local anesthetic into the fascial plane, is a simple and novel analgesia technique widely used due to its minimal risk of complications. ESPB has been tried in various surgeries; however, no study has reported its use in colorectal surgery. This study investigated whether ESPB could promote early recovery following laparoscopic colorectal surgery (LCS) by reducing opioid consumption and pain intensity. After randomization into the ESPB or control groups, an ultrasound-guided ESPB was performed at the thoracic 10th-11th level with 40 mL of 0.25% bupivacaine or normal saline. The ESPB group used less fentanyl during the initial 24 h after surgery (P = 0.004) and experienced less pain (P < 0.05 at all-time points) than the control group. The time to the first ambulation and the length of hospital stay were shorter in the ESPB group than in the control group (P = 0.015 and P = 0.008, respectively). In conclusion, ESPB could promote early recovery by reducing opioid consumption and pain intensity in patients receiving LCS.

Secreted Akkermansia muciniphila threonyl-tRNA synthetase functions to monitor and modulate immune homeostasis.

Commensal bacteria are critically involved in the establishment of tolerance against inflammatory challenges, the molecular mechanisms of which are just being uncovered. All kingdoms of life produce aminoacyl-tRNA synthetases (ARSs). Thus far, the non-translational roles of ARSs have largely been reported in eukaryotes. Here, we report that the threonyl-tRNA synthetase (AmTARS) of the gut-associated bacterium Akkermansia muciniphila is secreted and functions to monitor and modulate immune homeostasis. Secreted AmTARS triggers M2 macrophage polarization and orchestrates the production of anti-inflammatory IL-10 via its unique, evolutionary-acquired regions, which mediates specific interactions with TLR2. This interaction activates the MAPK and PI3K/AKT signaling pathways, which converge on CREB, leading to an efficient production of IL-10 and suppression of the central inflammatory mediator NF-κB. AmTARS restores IL-10-positive macrophages, increases IL-10 levels in the serum, and attenuates the pathological effects in colitis mice. Thus, commensal tRNA synthetases can act as intrinsic mediators that maintain homeostasis.

Electro-Biofabrication. Coupling Electrochemical and Biomolecular Methods to Create Functional Bio-Based Hydrogels.

Twenty years ago, this journal published a review entitled "Biofabrication with Chitosan" based on the observations that (i) chitosan could be electrodeposited using low voltage electrical inputs (typically less than 5 V) and (ii) the enzyme tyrosinase could be used to graft proteins (via accessible tyrosine residues) to chitosan. Here, we provide a progress report on the coupling of electronic inputs with advanced biological methods for the fabrication of biopolymer-based hydrogel films. In many cases, the initial observations of chitosan's electrodeposition have been extended and generalized: mechanisms have been established for the electrodeposition of various other biological polymers (proteins and polysaccharides), and electrodeposition has been shown to allow the precise control of the hydrogel's emergent microstructure. In addition, the use of biotechnological methods to confer function has been extended from tyrosinase conjugation to the use of protein engineering to create genetically fused assembly tags (short sequences of accessible amino acid residues) that facilitate the attachment of function-conferring proteins to electrodeposited films using alternative enzymes (e.g., transglutaminase), metal chelation, and electrochemically induced oxidative mechanisms. Over these 20 years, the contributions from numerous groups have also identified exciting opportunities. First, electrochemistry provides unique capabilities to impose chemical and electrical cues that can induce assembly while controlling the emergent microstructure. Second, it is clear that the detailed mechanisms of biopolymer self-assembly (i.e., chitosan gel formation) are far more complex than anticipated, and this provides a rich opportunity both for fundamental inquiry and for the creation of high performance and sustainable material systems. Third, the mild conditions used for electrodeposition allow cells to be co-deposited for the fabrication of living materials. Finally, the applications have been expanded from biosensing and lab-on-a-chip systems to bioelectronic and medical materials. We suggest that electro-biofabrication is poised to emerge as an enabling additive manufacturing method especially suited for life science applications and to bridge communication between our biological and technological worlds.

The incidence and clinical characteristics of myocarditis and pericarditis following mRNA-based COVID-19 vaccination in Republic of Korea adolescents from July 2021 to September 2022.

OBJECTIVES: Age-specific information regarding myocarditis/pericarditis in adolescents following mRNA-based coronavirus disease 2019 (COVID-19) vaccination in Asia remains insufficient. This study investigated the incidence and clinical characteristics of myocarditis/pericarditis in Republic of Korea adolescents after mRNA-based COVID-19 vaccination. METHODS: This retrospective descriptive study utilized patient data from the Korea Immunization Management System. Incidence rates were calculated according to age and sex. Clinical characteristics (symptoms/signs, laboratory values, and imaging results) were compared between mild and severe cases. RESULTS: Between July 19, 2021 and September 30, 2022, 3,728,224 individuals aged 12 to 19 years received 6,484,165 mRNA-based COVID-19 vaccines, and 173 cases met the case definition for myocarditis/pericarditis: 151 mild (87.3%) and 22 severe (12.7%). The incidence was 3.8-fold higher in males than in females. Troponin I/ troponin T was elevated in 96% of myocarditis cases, demonstrating higher sensitivity than creatine kinase-myocardial band (67.6%) or C-reactive protein (75.2%). ST-segment or Twave on electrography abnormalities were found in 60.3% (85/141). Paroxysmal/sustained atrial/ventricular arrhythmias were more common in severe than in mild cases (45.5% vs. 16.8%, p=0.008). Edema on T2-weighted magnetic imaging occurred in 21.6% (8/37) and 62.5% (5/8) of mild and severe cases, respectively (p=0.03). Abnormal pericardial fluid collection or pericardial inflammation was found in 75.4% of pericarditis cases (49/65). CONCLUSION: Myocarditis/pericarditis occurred in rare cases following mRNA-based COVID-19 vaccination. Most cases were mild, but the incidence was higher in adolescent males and after the second dose. As bivalent severe acute respiratory syndrome coronavirus 2 mRNA vaccination started in Republic of Korea in October 2022, the post-vaccination incidence of myocarditis/pericarditis should be closely monitored, considering clinical characteristics.

Rapid Screening and Comparison of Chimeric Lysins for Antibacterial Activity against Staphylococcus aureus Strains.

Chimeric lysins composed of various combinations of cell wall-lysing (enzymatic) and cell-wall-binding (CWB) domains of endolysins, autolysins, and bacteriocins have been developed as alternatives to or adjuvants of conventional antibiotics. The screening of multiple chimeric lysin candidates for activity via E. coli expression is not cost effective, and we previously reported on a simple cell-free expression system as an alternative. In this study, we sufficiently improved upon this cell-free expression system for use in screening activity via a turbidity reduction test, which is more appropriate than a colony reduction test when applied in multiple screening. Using the improved protocol, we screened and compared the antibacterial activity of chimeric lysin candidates and verified the relatively strong activity associated with the CHAP (cysteine, histidine-dependent amidohydrolase/peptidase) domain of secretory antigen SsaA-like protein (ALS2). ALS2 expressed in E. coli showed two major bands, and the smaller one (subprotein) was shown to be expressed by an innate downstream promoter and start codon (ATG). The introduction of synonymous mutations in the promoter resulted in clearly reduced expression of the subprotein, whereas missense mutations in the start codon abolished antibacterial activity as well as subprotein production. Interestingly, most of the S. aureus strains responsible for bovine mastitis were susceptible to ALS2, but those from human and chicken were less susceptible. Thus, the simple and rapid screening method can be applied to select functional chimeric lysins and define mutations affecting antibacterial activity, and ALS2 may be useful in itself and as a lead molecule to control bovine mastitis.

Detecting mpox infection in the early epidemic: an epidemiologic investigation of the third and fourth cases in Korea.

OBJECTIVES: As few mpox cases have been reported in Korea, we aimed to identify the characteristics of mpox infection by describing our epidemiologic investigation of a woman patient (index patient, the third case in Korea) and a physician who was infected by a needlestick injury (the fourth case). METHODS: We conducted contact tracing and exposure risk evaluation through interviews with these 2 patients and their physicians and contacts, as well as field investigations at each facility visited by the patients during their symptomatic periods. We then classified contacts into 3 levels according to their exposure risk and managed them to minimize further transmission by recommending quarantine and vaccination for post-exposure prophylaxis and monitoring their symptoms. RESULTS: The index patient had sexual contact with a man foreigner during a trip to Dubai, which was considered the probable route of transmission. In total, 27 healthcare-associated contacts across 7 healthcare facilities and 9 community contacts were identified. These contacts were classified into high (7 contacts), medium (9 contacts), and low (20 contacts) exposure risk groups. One high-risk contact was identified as a secondary patient: a physician who was injured while collecting specimens from the index patient. CONCLUSIONS: The index patient visited several medical facilities due to progressive symptoms prior to isolation. Although the 2022 mpox epidemic mainly affected young men, especially men who have sex with men, physicians should also consider mpox transmission in the general population for the timely detection of mpox-infected patients.

From Textile Coloring to Light-emitting Electrochemical Devices: Upcycling of the Isoviolanthrone Vat Dye.

Produced at ton scale, vat dyes are major environmental pollutants generated by the textile industry. However, they represent ideal and accessible candidates for chemical upcycling since they are usually composed of large π-conjugated scaffolds. Based on the valorization of "old" products, waste or even contaminant into high-added value goods, this concept can be easily transposed to the laboratories. As a contribution to the current environmental and ecological transition, we demonstrate herein the valorization/upcycling of wastewaters generated during the dyeing procedure. To do so, the reduced (leuco) form of vat violet 10, also known as isoviolanthrone, was functionalized to afford a readily soluble derivative that was subsequently and successfully used as active material in operating solution processed light-emitting electrochemical cells, that is, from textile dyeing to high-tech application.

Heating-mediated purification of active FGF21 and structure-based design of its variant with enhanced potency.

Fibroblast growth factor 21 (FGF21) has pharmaceutical potential against obesity-related metabolic disorders, including non-alcoholic fatty liver disease. Since thermal stability is a desirable factor for therapeutic proteins, we investigated the thermal behavior of human FGF21. FGF21 remained soluble after heating; thus, we examined its temperature-induced structural changes using circular dichroism (CD). FGF21 showed inter-convertible temperature-specific CD spectra. The CD spectrum at 100 °C returned to that at 20 °C when the heated FGF21 solution was cooled. Through loop swapping, the connecting loop between ß10 and ß12 in FGF21 was revealed to be associated with the unique thermal behavior of FGF21. According to surface plasmon resonance (SPR) experiments, in vitro cell-based assays, and model high-fat diet (HFD)-induced obesity studies, heated FGF21 maintained biological activities that were comparable to those of non-heated and commercial FGF21s. Based on sequence comparison and structural analysis, five point-mutations were introduced into FGF21. Compared with the wild type, the heated FGF21 variant displayed improved therapeutic potential in terms of body weight loss, the levels of hepatic triglycerides and lipids, and the degree of vacuolization of liver in HFD-fed mice.

Characteristics and related factors of waterborne and foodborne infectious disease outbreaks before and after the onset of the COVID-19 pandemic (2017-2021) in the Republic of Korea: a descriptive study.

BACKGROUND: The incidence of waterborne and foodborne infectious diseases (WFIDs) continues to increase annually, attracting significant global attention. This study examined trends in WFID outbreaks in the Republic of Korea over the 5-year period before and during the coronavirus disease 2019 (COVID-19) pandemic and provided foundational data to establish measures for the prevention and control of WFID outbreaks. METHODS: We analyzed 2,541 WFID outbreaks from 2017 to 2021 (42,805 cases) that were reported through the Integrated Disease Surveillance System of the Korea Disease Control and Prevention Agency. Outbreaks were defined as the occurrence of gastrointestinal symptoms in ≥2 individuals within a group with temporal and regional epidemiological associations. The related factors associated with WFID outbreaks during the observation period were statistically analyzed. RESULTS: The total number of WFID outbreaks significantly decreased in 2020 during the COVID-19 pandemic and increased to the pre-pandemic level in 2021. Different patterns were observed for each pathogen. The incidence of Salmonella outbreaks more than doubled, while norovirus outbreaks decreased significantly. CONCLUSION: WFID outbreaks in the Republic of Korea showed different patterns before and during the COVID-19 pandemic, influenced by infection control measures and changes in dietary consumption patterns. Outbreaks of some diseases increased, but the infection control measures applied during the pandemic resulted in a significant decrease in the overall number of WFID outbreaks. This highlights the importance of strengthening the management strategies for outbreak prevention through hygiene inspections, long-term monitoring, education, and promotion by conducting multidimensional analyses to understand the complex related factors.