Rational protein engineering to enhance MHC-independent T cell receptors.

Chimeric antigen receptor (CAR)-based therapies have pioneered synthetic cellular immunity but remain limited in their long-term efficacy. Emerging data suggest that dysregulated CAR-driven T cell activation causes T cell dysfunction and therapeutic failure. To re-engage the precision of the endogenous T cell response, we designed MHC-independent T cell receptors (miTCRs) by linking antibody variable domains to TCR constant chains. Using predictive modeling, we observed that this standard "cut and paste" approach to synthetic protein design resulted in myriad biochemical conflicts at the hybrid variable-constant domain interface. Through iterative modeling and sequence modifications we developed structure-enhanced miTCRs which significantly improved receptor-driven T cell function across multiple tumor models. We found that 41BB costimulation specifically prolonged miTCR T cell persistence and enabled improved leukemic control in vivo compared to classic CAR T cells. Collectively, we have identified core features of hybrid receptor structure responsible for regulating function.

Antimony-Platinum Modulated Contact Enabling Majority Carrier Polarity Selection on a Monolayer Tungsten Diselenide Channel.

We develop a novel metal contact approach using an antimony (Sb)-platinum (Pt) bilayer to mitigate Fermi-level pinning in 2D transition metal dichalcogenide channels. This strategy allows for control over the transport polarity in monolayer WSe2 devices. By adjustment of the Sb interfacial layer thickness from 10 to 30 nm, the effective work function of the contact/WSe2 interface can be tuned from 4.42 eV (p-type) to 4.19 eV (n-type), enabling selectable n-/p-FET operation in enhancement mode. The shift in effective work function is linked to Sb-Se bond formation and an emerging n-doping effect. This work demonstrates high-performance n- and p-FETs with a single WSe2 channel through Sb-Pt contact modulation. After oxide encapsulation, the maximum current density at |VD| = 1 V reaches 170 µA/µm for p-FET and 165 µA/µm for n-FET. This approach shows promise for cost-effective CMOS transistor applications using a single channel material and metal contact scheme.

Towards a better future for DNA barcoding: Evaluating monophyly- and distance-based species identification using COI gene fragments of Dacini fruit flies.

The utility of a universal DNA 'barcode' fragment (658 base pairs of the Cytochrome C Oxidase I [COI] gene) has been established as a useful tool for species identification, and widely criticized as one for understanding the evolutionary history of a group. Large amounts of COI sequence data have been produced that hold promise for rapid species identification, for example, for biosecurity. The fruit fly tribe Dacini holds about a thousand species, of which 80 are pests of economic concern. We generated a COI reference library for 265 species of Dacini containing 5601 sequences that span most of the COI gene using circular consensus sequencing. We compared distance metrics versus monophyly assessments for species identification and although we found a 'soft' barcode gap around 2% pairwise distance, the exceptions to this rule dictate that a monophyly assessment is the only reliable method for species identification. We found that all fragments regularly used for Dacini fruit fly identification >450 base pairs long provide similar resolution. 11.3% of the species in our dataset were non-monophyletic in a COI tree, which is mostly due to species complexes. We conclude with recommendations for the future generation and use of COI libraries. We revise the generic assignment of Dacus transversus stat. rev. Hardy 1982, and Dacus perpusillus stat. rev. Drew 1971 and we establish Dacus maculipterus White 1998 syn. nov. as a junior synonym of Dacus satanas Liang et al. 1993.

Features, measurements, determinants, treatments, and outcomes of musculoskeletal symptoms in postmenopausal women: A scoping review.

BACKGROUND: The literature lacks a consistent review of musculoskeletal symptoms in postmenopausal women. AIM: To identify features, measurements, determinants, treatments, and outcomes of musculoskeletal symptoms in postmenopausal women. METHOD: A scoping review was completed using six databases: Embase, Medline, Cochrane, CINAHL, Web of Science, and Scopus up to December 2022. Sixty-three articles were identified. RESULTS: Musculoskeletal symptoms in postmenopausal women include somatic symptoms of non-specific origin, upper and lower limb symptoms, spinal pain, and decline in physical performance. Measurements were categorized into four groups: musculoskeletal symptoms for menopause, general musculoskeletal symptoms, menopause-specific quality of life, and general quality of life questionnaires. The determinants were grouped into four themes: demographics, physical determinants, psychosocial determinants, and lifestyle. Pharmacological interventions, supplementation options, and exercise regimens exist for postmenopausal women with musculoskeletal symptoms. CONCLUSION: A comprehensive policy is needed to address musculoskeletal symptoms in postmenopausal women, promoting diverse treatments for improved quality of life.

How to Prevent Nerve Root Injury in Uniportal Full Endoscopic Lumbar Fusion Surgery? Insights from a Cadaveric Anatomical Study with Simulation Surgery.

STUDY DESIGN: The study included two fresh-frozen cadavers. OBJECTIVE: To elucidate the positional relationship between surgical instruments and nerve roots during full endoscopic facet-sparing (FE fs-TLIF) and facet-resecting (FE fr-TLIF) lumbar interbody fusion and propose safe instrumentation insertion procedures and recommend cage glider designs aimed at protecting nerve roots. SUMMARY OF BACKGROUND DATA: Endoscopic surgical techniques are increasingly used for minimally invasive lumbar fusion surgery with FE fr-TLIF and FE fs-TLIF being common approaches. However, the risk of nerve root injury remains a significant concern during these procedures. METHODS: Eight experienced endoscopic spine surgeons performed uniportal FE fr-TLIF and FE fs-TLIF on cadaveric lumbar spines, totaling 16 surgeries. Post-operation, soft tissues were removed to assess the positional relationship between the cage entry point and nerve roots. Distances between the cage entry point, traversing nerve root, and exiting nerve root were measured. Safe instrumentation design and insertion procedures were determined. RESULTS: In FE fr-TLIF, the mean distance between the cage entry point and traversing nerve root was significantly shorter compared to FE fs-TLIF (3.30±1.35 mm vs. 8.58±2.47 mm, respectively; P<0.0001). Conversely, the mean distance between the cage entry point and the exiting nerve root was significantly shorter in FE fs-TLIF compared to FE fr-TLIF (3.73±1.97 mm vs. 6.90±1.36 mm, respectively; P<0.0001). For FE fr-TLIF, prioritizing the protection of the traversing root using a two-bevel tip cage glider was crucial. In contrast, for FE fs-TLIF, a single-bevel tip cage glider placed in the caudal location was recommended. CONCLUSION: This study elucidates the anatomical relationship between cage entry points and nerve roots in uniportal endoscopic lumbar fusion surgery. Protection strategies should prioritize the traversing root in FE fr-TLIF and the exiting root in FE fs-TLIF, with corresponding variations in surgical techniques. LEVEL OF EVIDENCE: V.

Efficacy of Lactococcus lactis subsp. lactis LY-66 and Lactobacillus plantarum PL-02 in Enhancing Explosive Strength and Endurance: A Randomized, Double-Blinded Clinical Trial.

Probiotics are posited to enhance exercise performance by influencing muscle protein synthesis, augmenting glycogen storage, and reducing inflammation. This double-blind study randomized 88 participants to receive a six-week intervention with either a placebo, Lactococcus lactis subsp. lactis LY-66, Lactobacillus plantarum PL-02, or a combination of both strains, combined with a structured exercise training program. We assessed changes in maximal oxygen consumption (VO2max), exercise performance, and gut microbiota composition before and after the intervention. Further analyses were conducted to evaluate the impact of probiotics on exercise-induced muscle damage (EIMD), muscle integrity, and inflammatory markers in the blood, 24 and 48 h post-intervention. The results demonstrated that all probiotic groups exhibited significant enhancements in exercise performance and attenuation of muscle strength decline post-exercise exhaustion (p < 0.05). Notably, PL-02 intake significantly increased muscle mass, whereas LY-66 and the combination therapy significantly reduced body fat percentage (p < 0.05). Analysis of intestinal microbiota revealed an increase in beneficial bacteria, especially a significant rise in Akkermansia muciniphila following supplementation with PL-02 and LY-66 (p < 0.05). Overall, the combination of exercise training and supplementation with PL-02, LY-66, and their combination improved muscle strength, explosiveness, and endurance performance, and had beneficial effects on body composition and gastrointestinal health, as evidenced by data obtained from non-athlete participants.

Superior sequence-controlled poly(L-lactide)-based bioplastic with tunable seawater biodegradation.

Developing superior-performance marine-biodegradable plastics remains a critical challenge in mitigating marine plastic pollution. Commercially available biodegradable polymers, such as poly(L-lactide) (PLA), undergo slow degradation in complex marine environments. This study introduces an innovative bioplastic design that employs a facile ring-opening and coupling reaction to incorporate hydrophilic polyethylene glycol (PEG) into PLA, yielding PEG-PLA copolymers with either sequence-controlled alternating or random structures. These materials exhibit exceptional toughness in both wet and dry states, with an elongation at break of 1446.8% in the wet state. Specifically, PEG4kPLA2k copolymer biodegraded rapidly in proteinase K enzymatic solutions and had a significant weight loss of 71.5% after 28 d in seawater. The degradation primarily affects the PLA segments within the PEG-PLA copolymer, as evidenced by structural changes confirmed through comprehensive characterization techniques. The seawater biodegradability, in line with the Organization for Economic Cooperation and Development 306 Marine biodegradation test guideline, reached 72.63%, verified by quantitative biochemical oxygen demand analysis, demonstrating rapid chain scission in marine environments. The capacity of PEG-PLA bioplastic to withstand DI water and rapidly biodegrade in seawater makes it a promising candidate for preventing marine plastic pollution.

Direct Identification of Intact Proteins Using a Low-Resolution Mass Spectrometer with CIDn/ETnoD.

Over the past decades, proteomics has become increasingly important and a heavily discussed topic. The identification of intact proteins remains a major focus in this field. While most intact proteins are analyzed using high-resolution mass spectrometry, identifying them through low-resolution mass spectrometry continues to pose challenges. In our study, we investigated the capability of identifying various intact proteins using collision-induced dissociation (CID) and electron transfer without dissociation (ETnoD). Using myoglobin as our test protein, stable product ions were generated with CID, and the identities of the product ions were identified with ETnoD. ETnoD uses a short activation time (AcT, 5 ms) to create sequential charge-reduced precursor ion (CRI). The charges of the fragments and their sequences were determined with corresponding CRI. The product ions can be selected for subsequent CID (termed CIDn) combined with ETnoD for further sequence identification and validation. We refer to this method as CIDn/ETnoD. The use of a multistage CID activation (CIDn) and ETnoD protocol has been applied to several intact proteins to obtain multiple sequence identifications.

Comparison of laparoscopic and open surgery for colorectal malignancy in obese patients: a propensity score-weighted cohort study.

BACKGROUND: Insufficient evidence exists to ascertain the long-term prognosis in patients with obesity undergoing laparoscopic surgery versus open surgery for colorectal cancer. METHODS: Employing an institutional database from 2009 to 2019, we assessed individuals with a body mass index of ≥30 kg/m2 who underwent surgery for primary stage I-III colorectal adenocarcinoma. We used propensity score-weighted analysis to compare short-term and oncologic outcomes between laparoscopic and open surgical approaches. RESULTS: This study enrolled 473 patients (open vs. laparoscopic surgery: 220 vs. 253; median follow-up period, 60 mo). The laparoscopy group showed a significantly longer operative time (252 vs. 212 min), a higher anastomotic-leakage rate (5.14% vs. 0.91%), and a greater proportion of Clavien-Dindo class > III complications (5.93% vs. 1.82%). The open group showed a higher wound infection rate (7.27% vs. 3.16%) and a higher readmission rate (6.36% vs. 2.37%). After propensity-score weighting, laparoscopy was inferior to open surgery in terms of long-term overall survival (hazard ratio: 1.43), disease-free survival (1.39), and recurrence rate (21.1% vs. 14.5%). In the subgroup analysis, female patients, older individuals, stage III patients, patients with rectal cancer, and those who underwent surgery after 2014 showed inferior long-term outcomes after laparoscopy. CONCLUSIONS: Laparoscopic colorectal cancer surgery for patients with obesity requires significant caution. Despite good short-term outcomes, this procedure is associated with hidden risks and poor long-term prognoses. In female patients, older individuals, stage III patients, patients with rectal cancer, and those treated in the late surgery era subgroups, caution is advised when performing laparoscopic surgery.

Study on different isolation technology on the performance of blue micro-LEDs array applications.

In this study, a 3 × 3 blue micro-LED array with a pixel size of 10 × 10 µm2 and a pitch of 15 µm was fabricated on an epilayer grown on a sapphire substrate using metalorganic chemical vapor deposition technology. The fabrication process involved photolithography, wet and dry etching, E-beam evaporation, and ion implantation technology. Arsenic multi-energy implantation was utilized to replace the mesa etching for electrical isolation, where the implantation depth increased with the average energy. Different ion depth profiles had varying effects on electrical properties, such as forward current and leakage currents, potentially causing damage to the n-GaN layer and increasing the series resistance of the LEDs. As the implantation depth increased, the light output power and peak external quantum efficiency of the LEDs also increased, improving from 5.33 to 9.82%. However, the efficiency droop also increased from 46.3 to 48.6%.

Low Levels of IgM Recognizing 4-Hydroxy-2-Nonenal-Modified Apolipoprotein A-I Peptide and Its Association with the Severity of Coronary Artery Disease in Taiwanese Patients.

Autoantibodies against apolipoprotein A-I (ApoA-I) are associated with cardiovascular disease risks. We aimed to examine the 4-hydroxy-2-nonenal (HNE) modification of ApoA-I in coronary artery disease (CAD) and evaluate the potential risk of autoantibodies against their unmodified and HNE-modified peptides. We assessed plasma levels of ApoA-I, HNE-protein adducts, and autoantibodies against unmodified and HNE-peptide adducts, and significant correlations and odds ratios (ORs) were examined. Two novel CAD-specific HNE-peptide adducts, ApoA-I251-262 and ApoA-I70-83, were identified. Notably, immunoglobulin G (IgG) anti-ApoA-I251-262 HNE, IgM anti-ApoA-I70-83 HNE, IgG anti-ApoA-I251-262, IgG anti-ApoA-I70-83, and HNE-protein adducts were significantly correlated with triglycerides, creatinine, or high-density lipoprotein in CAD with various degrees of stenosis (<30% or >70%). The HNE-protein adduct (OR = 2.208-fold, p = 0.020) and IgM anti-ApoA-I251-262 HNE (2.046-fold, p = 0.035) showed an increased risk of progression from >30% stenosis in CAD. HNE-protein adducts and IgM anti-ApoA-I251-262 HNE may increase the severity of CAD at high and low levels, respectively.

Investigation of the Microbial Diversity in the Oryza sativa Cultivation Environment and Artificial Transplantation of Microorganisms to Improve Sustainable Mycobiota.

Rice straw is not easy to decompose, it takes a long time to compost, and the anaerobic bacteria involved in the decomposition process produce a large amount of carbon dioxide (CO2), indicating that applications for rice straw need to be developed. Recycling rice straw in agricultural crops is an opportunity to increase the sustainability of grain production. Several studies have shown that the probiotic population gradually decreases in the soil, leading to an increased risk of plant diseases and decreased biomass yield. Because the microorganisms in the soil are related to the growth of plants, when the soil microbial community is imbalanced it seriously affects plant growth. We investigated the feasibility of using composted rice stalks to artificially cultivate microorganisms obtained from the Oryza sativa-planted environment for analyzing the mycobiota and evaluating applications for sustainable agriculture. Microbes obtained from the water-submerged part (group-A) and soil part (group-B) of O. sativa were cultured in an artificial medium, and the microbial diversity was analyzed with internal transcribed spacer sequencing. Paddy field soil was mixed with fermented paddy straw compost, and the microbes obtained from the soil used for O. sativa planting were designated as group-C. The paddy fields transplanted with artificially cultured microbes from group-A were designated as group-D and those from group-B were designated as group-E. We found that fungi and yeasts can be cultured in groups-A and -B. These microbes altered the soil mycobiota in the paddy fields after transplantation in groups-D and -E compared to groups-A and -B. Development in O. sativa post treatment with microbial transplantation was observed in the groups-D and -E compared to group-C. These results showed that artificially cultured microorganisms could be efficiently transplanted into the soil and improve the mycobiota. Phytohormones were involved in improving O. sativa growth and rice yield via the submerged part-derived microbial medium (group-D) or the soil part-derived microbial medium (group-E) treatments. Collectively, these fungi and yeasts may be applied in microbial transplantation via rice straw fermentation to repair soil mycobiota imbalances, facilitating plant growth and sustainable agriculture. These fungi and yeasts may be applied in microbial transplantation to repair soil mycobiota imbalances and sustainable agriculture.

Glucosamine and Silibinin Alter Cartilage Homeostasis through Glycosylation and Cellular Stresses in Human Chondrocyte Cells.

Osteoarthritis is more prevalent than any other form of arthritis and is characterized by the progressive mechanical deterioration of joints. Glucosamine, an amino monosaccharide, has been used for over fifty years as a dietary supplement to alleviate osteoarthritis-related discomfort. Silibinin, extracted from milk thistle, modifies the degree of glycosylation of target proteins, making it an essential component in the treatment of various diseases. In this study, we aimed to investigate the functional roles of glucosamine and silibinin in cartilage homeostasis using the TC28a2 cell line. Western blots showed that glucosamine suppressed the N-glycosylation of the gp130, EGFR, and N-cadherin proteins. Furthermore, both glucosamine and silibinin differentially decreased and increased target proteins such as gp130, Snail, and KLF4 in TC28a2 cells. We observed that both compounds dose-dependently induced the proliferation of TC28a2 cells. Our MitoSOX and DCFH-DA dye data showed that 1 µM glucosamine suppressed mitochondrial reactive oxygen species (ROS) generation and induced cytosol ROS generation, whereas silibinin induced both mitochondrial and cytosol ROS generation in TC28a2 cells. Our JC-1 data showed that glucosamine increased red aggregates, resulting in an increase in the red/green fluorescence intensity ratio, while all the tested silibinin concentrations increased the green monomers, resulting in decreases in the red/green ratio. We observed increasing subG1 and S populations and decreasing G1 and G2/M populations with increasing amounts of glucosamine, while increasing amounts of silibinin led to increases in subG1, S, and G2/M populations and decreases in G1 populations in TC28a2 cells. MTT data showed that both glucosamine and silibinin induced cytotoxicity in TC28a2 cells in a dose-dependent manner. Regarding endoplasmic reticulum stress, both compounds induced the expression of CHOP and increased the level of p-eIF2α/eIF2α. With respect to O-GlcNAcylation status, glucosamine and silibinin both reduced the levels of O-GlcNAc transferase and hypoxia-inducible factor 1 alpha. Furthermore, we examined proteins and mRNAs related to these processes. In summary, our findings demonstrated that these compounds differentially modulated cellular proliferation, mitochondrial and cytosol ROS generation, the mitochondrial membrane potential, the cell cycle profile, and autophagy. Therefore, we conclude that glucosamine and silibinin not only mediate glycosylation modifications but also regulate cellular processes in human chondrocytes.

Complement decay-accelerating factor inhibits inflammation-induced myopia development.

Myopia is regarded as a worldwide epidemic ocular disease, has been proved related to inflammation. CD55, also known as decay-accelerating factor (DAF) can modulate the activation of complement through inhibiting the formation of complement 3 convertase and its dysregulation is involved in various inflammatory diseases. To investigate the association between CD55 and myopia, and to test whether CD55 can inhibit myopia development by suppressing inflammation in the eye, we use three different animal models including monocular form-deprivation myopia, myopia induced by TNF-α administration and allergic conjunctivitis animal model to reveal the CD55 in myopia development. The tears of thirty-eight participants with different spherical equivalents were collected and CD55 in the tears were also analyzed. Complement 3 and complement 5 levels increased while CD55 levels decreased in allergic conjunctivitis and myopic eyes. After anti-inflammatory drugs administration, CD55 expression was increased in monocular form-deprivation myopia model. We also found inflammatory cytokines TGF-ß, IL-6, TNF-α, and IL-1ß may enhance complement 3 and complement 5 activation while CD55 level was suppressed contrary. Moreover, lower CD55 levels were found in the tears of patients with myopia with decreased diopter values. Finally, CD55-Fc administration on the eyelids can inhibit the elongation of axial length and change of refractive error. CD55-Fc application also suppress myopia development subsequent to complement 3 and complement 5 reduction and can lower myopia-specific (MMP-2 and TGF-ß) cytokine expression in TNF-α induced myopia animal model. This suggests that CD55 can inhibit myopia development by suppression of complement activation and eventual down-regulation of inflammation.

Chlorpyrifos-induced suppression of the antioxidative defense system leads to cytotoxicity and genotoxicity in macrophages.

Chlorpyrifos, widely used for pest control, is known to have various harmful effects, although its toxic effects in macrophages and the mechanisms underlying its toxicity remain unclear. The present study investigated the toxic effects of chlorypyrifos in a macrophage cell line. Here, we found that chlorpyrifos induced cytotoxicity and genotoxicity in RAW264.7 macrophages. Moreover, chlorpyrifos induced intracellular ROS production, subsequently leading to lipid peroxidation. Chlorpyrifos reduced the activation of antioxidative enzymes including superoxide dismutase, catalase, and glutathione peroxidase. Chlorpyrifos upregulated HO-1 expression and activated the Keap1-Nrf2 pathway, as indicated by enhanced Nrf2 phosphorylation and Keap1 degradation. Chlorpyrifos exerted effects on the following in a dose-dependent manner: cytotoxicity, genotoxicity, lipid peroxidation, intracellular ROS production, antioxidative enzyme activity reduction, HO-1 expression, Nrf2 phosphorylation, and Keap1 degradation. Notably, N-acetyl-L-cysteine successfully inhibited chlorpyrifos-induced intracellular ROS generation, cytotoxicity, and genotoxicity. Thus, chlorpyrifos may induce cytotoxicity and genotoxicity by promoting intracellular ROS production and suppressing the antioxidative defense system activation in macrophages.

Temporal trends of food consumption patterns in Tuvalu under the context of climate change: COMmunity-based Behavior and Attitude survey in Tuvalu (COMBAT) since 2020.

AIM: The aim of this study was to analyze temporal trends of food consumption patterns, attitudes, and health-related knowledge in Tuvalu, a small Pacific Island country facing the triple threat of obesity, climate change, and food insecurity. METHODS: Two waves of the COMmunity-based Behavior and Attitude (COMBAT) survey were conducted in 2020 and 2022. Descriptive characteristics of changes in obesity proportion, food intake, and sociodemographic factors were assessed. Additionally, this study also integrates individual climate data utilizing satellite-based prediction models, and estimates historical temperature, precipitation, and sea level trends among all islands in Tuvalu. RESULTS: The study revealed a high obesity proportion among adults (69.5% in 2020, 73.2% in 2022) and an increase in the percentage of adolescents with a high waist circumference. Variations in food intake were also observed between the two waves of the survey. CONCLUSIONS: The data collected in the COMBAT study provides valuable insights for future epidemiological research to elucidate the associations and causal relationships between climate change, food security, and non-communicable diseases in Tuvalu.

Study of a Deep Convolution Network with Enhanced Region Proposal Network in the Detection of Cancerous Lung Tumors.

A deep convolution network that expands on the architecture of the faster R-CNN network is proposed. The expansion includes adapting unsupervised classification with multiple backbone networks to improve the Region Proposal Network in order to improve accuracy and sensitivity in detecting minute changes in images. The efficiency of the proposed architecture is investigated by applying it to the detection of cancerous lung tumors in CT (computed tomography) images. This investigation used a total of 888 images from the LUNA16 dataset, which contains CT images of both cancerous and non-cancerous tumors of various sizes. These images are divided into 80% and 20%, which are used for training and testing, respectively. The result of the investigation through the experiment is that the proposed deep-learning architecture could achieve an accuracy rate of 95.32%, a precision rate of 94.63%, a specificity of 94.84%, and a high sensitivity of 96.23% using the LUNA16 images. The result shows an improvement compared to a reported accuracy of 93.6% from a previous study using the same dataset.

Optimizing aesthetic results in Asian women with giant phyllodes tumors over 10 cm: the periareolar mastopexy approach.

Giant phyllodes tumors, typically exceeding 10 cm in size, are neoplastic lesions with malignant potential. Surgical excision in small-breasted Asian women presents unique challenges where expected poor aesthetic outcomes may delay timely medical intervention. The periareolar mastopexy technique offers a comprehensive solution, enabling complete tumor removal alongside mastopexy to achieve optimal breast contouring. This approach consistently delivers favorable aesthetic outcomes, enhancing symmetry and contour. Additionally, the periareolar approach minimizes visible scarring, thereby enhancing patient satisfaction with the cosmetic outcome. Herein, we present a case report of Asian women with giant phyllodes tumors exceeding 10 cm, successfully managed using the periareolar mastopexy technique, emphasizing the importance of optimizing aesthetic outcomes in these challenging cases.

Pacing Strategies in Elite Individual-Medley Swimmers: A Decision-Tree Approach.

PURPOSE: This study aimed to examine pacing strategies and identify the stroke that has the most significant impact on overall performance in men's and women's 200-m and 400-m individual-medley events from 2000 to 2021. METHODS: The time in each lap and overall race was retrieved from the World Aquatics website. The standardized time for each stroke in individual medley was calculated by dividing the actual time by a reference time specific to each stroke. The reference time was derived from the respective laps in single-stroke finals in the 2017 World Swimming Championships. The decision-tree method was used for analysis. The dependent variables were qualified or nonqualified in heats and semifinals, and winning medals in finals. The independent variables were the ratio of standardized time in each stroke to the sum of standardized time in all 4 strokes. RESULTS: Swimmers who spent a higher ratio of standardized time in the butterfly stroke (>0.236-0.245) are associated with a higher likelihood of winning medals or qualifying for the next stage in most men's and women's 200-m and 400-m individual medley. Butterfly exhibited the highest normalized importance that distinguished medalists from nonmedalists in the finals. The front-crawl stroke is the second most important determinant in medalists in men's and women's 200-m individual medley, whereas backstroke and breaststroke were the second most important in men's and women's 400-m individual medley, respectively. CONCLUSION: Individual-medley swimmers who were excellent in butterfly and conserved energy in butterfly had a higher likelihood of success.

Protective Effects of Pear Extract on Skin from In Vitro and In Vivo UVA-Induced Damage.

The ancient Chinese medical book "Compendium of Materia Medica" records that pears can relieve symptoms of respiratory-related diseases. Previous research has shown that pear Pyrus Pyrifolia (Burm.f.) Nakai has antioxidant and anti-inflammatory properties. However, the anti-inflammatory, antioxidant, and anti-photoaging protective effects of Pyrus pyrifolia (Burm.f.) Nakai seed components have not been studied. Ultraviolet light (UV) causes skin inflammation, damages the skin barrier, and is an important cause of skin photoaging. Therefore, UV light with a wavelength of 365 nm was used to irradiate HaCaT and mice. Western blot, real-time quantitative polymerase chain reaction, and fluorescence imaging system were used to explore its anti-UVA mechanism. Dialysis membrane and nuclear magnetic resonance were used for the chemical constituent analysis of pear seed water extract (PSWE). We found that PSWE can significantly reduce UVA-induced skin cell death and mitogen-activated protein kinase phosphorylation and can inhibit the mRNA expression of UVA-induced cytokines (including IL-1ß, IL-6, and TNF-α). In addition, PSWE can also reduce the generation of oxidative stress within skin cells. In vivo experimental studies found that PSWE pretreatment effectively reduced transepidermal water loss, inflammation, redness, and dryness in hairless mice. The molecular weight of the active part of pear water extract is approximately 384. Based on the above results, we first found that pear seeds can effectively inhibit oxidative stress and damage caused by UVA. It is a natural extract with antioxidant properties and anti-aging activity that protects skin cells and strengthens the skin barrier.