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1.
Sci Total Environ ; : 176255, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39276993

ABSTRACT

Air pollution, particularly fine particulate matter (PM2.5) with <2.5 µm in diameter, is a major public health concern. Studies have consistently linked PM2.5 exposure to a heightened risk of cardiovascular diseases (CVDs) such as ischemic heart disease (IHD), heart failure (HF), and cardiac arrhythmias. Notably, individuals with pre-existing age-related cardiometabolic conditions appear more susceptible. However, the specific impact of PM2.5 on CVDs susceptibility in older adults remains unclear. Therefore, this review addresses this gap by discussing the factors that make the elderly more vulnerable to PM2.5-induced CVDs. Accordingly, we focused on physiological aging, increased susceptibility, cardiometabolic risk factors, CVDs, and biological mechanisms. This review concludes by examining potential interventions to reduce exposure and the adverse health effects of PM2.5 in the elderly population. The latter includes dietary modifications, medications, and exploration of the potential benefits of supplements. By comprehensively analyzing these factors, this review aims to provide a deeper understanding of the detrimental effects of PM2.5 on cardiovascular health in older adults. This knowledge can inform future research and guide strategies to protect vulnerable populations from the adverse effects of air pollution.

2.
RSC Adv ; 14(40): 29455-29463, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39297044

ABSTRACT

Background: Guided bone regeneration (GBR) uses bone grafts and barrier membranes to block soft tissue invasion and eventually create a new bone. Some studies indicate that a porcine bone graft demonstrates excellent biocompatibility and holds promise as a xenograft for GBR. However, only a few studies have investigated the effectiveness of this biomaterial after magnesium coating in improving osteoblast performance. Aim: This study aimed to prove that the hydrothermal method can be used to coat magnesium oxide (MgO) on the surface of a porcine graft and enhance the biomaterial's property for better osteogenic differentiation of osteoblasts in vitro. Materials and Method: A porcine bone graft was produced, and the hydrothermal method was used to coat 2 mM and 5 mM of MgO on the graft. Material physiochemistry and biocompatibility analyses were performed at days 1, 3, and 5. Results: pH value assay results suggested that MgO slightly increased the alkalinity of the graft. SEM images showed that MgO with some surface roughness was coated on the porcine bone surface, and EDX indicated that the Mg and O element percentages increased by about 5% and 9%, respectively. The porcine graft coated with MgO was rougher than an uncoated porcine graft. FTIR analysis of the porcine graft implied that its chemical structure did not change due to MgO hydrothermal processing. Cell viability assay illustrated the highest cell proliferation with the porcine graft with 5 mM MgO (P < 0.001), and good cell attachment was observed on the graft with immunofluorescence using confocal laser scanning microscopy. Cell differentiation assay results revealed that the porcine graft with 5 mM MgO had the highest alkaline phosphate activity (P < 0.0001) among the uncoated porcine graft and the porcine graft with 2 mM MgO. Relative quantitative polymerase chain reaction (qPCR) at days 1 and 5 revealed upregulated osteoblast gene expression with a statistically significant difference. Conclusion: The porcine graft hydrothermally coated with 5 mM MgO was more biocompatible and enhanced osteoblast differentiation. Thus, the findings of this study indicate that a porcine graft with 5 mM MgO has great potential as a bio-bone graft for guided bone regeneration.

3.
Nat Commun ; 15(1): 7463, 2024 Aug 29.
Article in English | MEDLINE | ID: mdl-39198443

ABSTRACT

Most cancer cells reprogram their glucose metabolic pathway from oxidative phosphorylation to aerobic glycolysis for energy production. By reducing enzyme activity of pyruvate kinase M2 (PKM2), cancer cells attain a greater fraction of glycolytic metabolites for macromolecule synthesis needed for rapid proliferation. Here we demonstrate that hydrogen sulfide (H2S) destabilizes the PKM2 tetramer into monomer/dimer through sulfhydration at cysteines, notably at C326, leading to reduced PKM2 enzyme activity and increased PKM2-mediated transcriptional activation. Blocking PKM2 sulfhydration at C326 through amino acid mutation stabilizes the PKM2 tetramer and crystal structure further revealing the tetramer organization of PKM2-C326S. The PKM2-C326S mutant in cancer cells rewires glucose metabolism to mitochondrial respiration, significantly inhibiting tumor growth. In this work, we demonstrate that PKM2 sulfhydration by H2S inactivates PKM2 activity to promote tumorigenesis and inhibiting this process could be a potential therapeutic approach for targeting cancer metabolism.


Subject(s)
Glucose , Hydrogen Sulfide , Hydrogen Sulfide/metabolism , Humans , Glucose/metabolism , Animals , Cell Line, Tumor , Mice , Pyruvate Kinase/metabolism , Pyruvate Kinase/genetics , Pyruvate Kinase/chemistry , Cysteine/metabolism , Glycolysis , Thyroid Hormones/metabolism , Mutation , Mitochondria/metabolism , Neoplasms/metabolism , Neoplasms/genetics , Neoplasms/pathology , Protein Multimerization , Mice, Nude , Carrier Proteins/metabolism , Carrier Proteins/genetics , Membrane Proteins/metabolism , Membrane Proteins/genetics , Thyroid Hormone-Binding Proteins
4.
Metab Brain Dis ; 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39120851

ABSTRACT

This study explores the role and mechanism of Annexin-A1 Tripeptide (ANXA1sp) in mitigating neuronal damage and promoting functional recovery in a mouse model of traumatic brain injury (TBI). Our goal is to identify ANXA1sp as a potential therapeutic drug candidate for TBI treatment. Adult male C57BL/6J mice were subjected to controlled cortical impact (CCI) to simulate TBI, supplemented by an in vitro model of glutamate-induced TBI in HT22 cells.  We assessed neurological deficits using the Modified Neurological Severity Score (mNSS), tested sensorimotor functions with beam balance and rotarod tests, and evaluated cognitive performance via the Morris water maze. Neuronal damage was quantified using Nissl and TUNEL staining, while microglial activation and inflammatory responses were measured through immunostaining, quantitative PCR (qPCR), Western blotting, and ELISA. Additionally, we evaluated cell viability in response to glutamate toxicity using the Cell Counting Kit-8 (CCK-8) assay and lactate dehydrogenase (LDH) release. Intraperitoneal administration of ANXA1sp significantly enhanced neurological outcomes, markedly reducing sensorimotor and cognitive impairments caused by TBI. This treatment resulted in a significant reduction in lesion volume and decreased neuronal cell death in the ipsilateral cortex. Moreover, ANXA1sp effectively diminished microglial activation around the brain lesion and decreased the levels of pro-inflammatory markers such as IL-6, IL-1ß, TNF-α, and TGF-ß in the cortex, indicating a significant reduction in neuroinflammation post-TBI. ANXA1sp also offered protection against neuronal cell death induced by glutamate toxicity, primarily by inhibiting the nuclear translocation of ANXA1, highlighting its potential as a neuroprotective strategy in TBI management. Administration of ANXA1sp significantly reduced neuroinflammation and neuronal cell death, primarily by blocking the nuclear translocation of ANXA1. This treatment substantially reduced brain damage and improved neurological functional recovery after TBI. Consequently, ANXA1sp stands out as a promising neuroprotective agent for TBI therapy.

5.
Sensors (Basel) ; 24(15)2024 Aug 03.
Article in English | MEDLINE | ID: mdl-39124084

ABSTRACT

The sturgeon is an important commercial aquaculture species in China. The measurement of sturgeon mass plays a remarkable role in aquaculture management. Furthermore, the measurement of sturgeon mass serves as a key phenotype, offering crucial information for enhancing growth traits through genetic improvement. Until now, the measurement of sturgeon mass is usually conducted by manual sampling, which is work intensive and time consuming for farmers and invasive and stressful for the fish. Therefore, a noninvasive volume reconstruction model for estimating the mass of swimming sturgeon based on RGB-D sensor was proposed in this paper. The volume of individual sturgeon was reconstructed by integrating the thickness of the upper surface of the sturgeon, where the difference in depth between the surface and the bottom was used as the thickness measurement. To verify feasibility, three experimental groups were conducted, achieving prediction accuracies of 0.897, 0.861, and 0.883, which indicated that the method can obtain the reliable, accurate mass of the sturgeon. The strategy requires no special hardware or intensive calculation, and it provides a key to uncovering noncontact, high-throughput, and highly sensitive mass evaluation of sturgeon while holding potential for evaluating the mass of other cultured fishes.


Subject(s)
Aquaculture , Fishes , Swimming , Animals , Fishes/physiology , Swimming/physiology , Aquaculture/methods
6.
J Med Cases ; 15(8): 201-207, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39091571

ABSTRACT

Aspirin hypersensitivity continues to be a major clinical challenge in patients with coronary artery disease (CAD), particularly in those requiring percutaneous coronary intervention (PCI) in the absence of a validated alternative antiplatelet regimen. Although true aspirin allergies are uncommon, they can manifest with severe reactions such as angioedema or anaphylaxis, highlighting the critical role of diagnostic challenge tests and tolerance induction strategies. Here, a 61-year-old female with end-stage renal disease (ESRD) on hemodialysis presented with new-onset heart failure and elevated troponins in the setting of a hypertensive emergency. A subsequent left heart catheterization revealed severe multivessel disease, but PCI was deferred due to her history suggestive of aspirin-induced angioedema and the absence of a known optimal approach in this scenario. Given the feasibility of completing a desensitization protocol, aspirin desensitization was pursued, facilitating the successful placement of a drug-eluting stent. This case highlights the need for validated protocols to manage aspirin hypersensitivity, as the current treatment paradigm necessitates a highly individualized approach by the treating clinician.

7.
Neuron ; 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39121859

ABSTRACT

Primary familial brain calcification (PFBC) is a genetic neurological disease, yet no effective treatment is currently available. Here, we identified five novel intronic variants in SLC20A2 gene from six PFBC families. Three of these variants increased aberrant SLC20A2 pre-mRNA splicing by altering the binding affinity of splicing machineries to newly characterized cryptic exons, ultimately causing premature termination of SLC20A2 translation. Inhibiting the cryptic-exon incorporation with splice-switching ASOs increased the expression levels of functional SLC20A2 in cells carrying SLC20A2 mutations. Moreover, by knocking in a humanized SLC20A2 intron 2 sequence carrying a PFBC-associated intronic variant, the SLC20A2-KI mice exhibited increased inorganic phosphate (Pi) levels in cerebrospinal fluid (CSF) and progressive brain calcification. Intracerebroventricular administration of ASOs to these SLC20A2-KI mice reduced CSF Pi levels and suppressed brain calcification. Together, our findings expand the genetic etiology of PFBC and demonstrate ASO-mediated splice modulation as a potential therapy for PFBC patients with SLC20A2 haploinsufficiency.

8.
Nat Commun ; 15(1): 6713, 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39112462

ABSTRACT

Doped van der Waals heterostructures host layer-hybridized trions, i.e. charged excitons with layer-delocalized constituents holding promise for highly controllable optoelectronics. Combining a microscopic theory with photoluminescence (PL) experiments, we demonstrate the electrical tunability of the trion energy landscape in naturally stacked WSe2 bilayers. We show that an out-of-plane electric field modifies the energetic ordering of the lowest lying trion states, which consist of layer-hybridized Λ -point electrons and layer-localized K-point holes. At small fields, intralayer-like trions yield distinct PL signatures in opposite doping regimes characterized by weak Stark shifts in both cases. Above a doping-asymmetric critical field, interlayer-like species are energetically favored and produce PL peaks with a pronounced Stark red-shift and a counter-intuitively large intensity arising from efficient phonon-assisted recombination. Our work presents an important step forward in the microscopic understanding of layer-hybridized trions in van der Waals heterostructures and paves the way towards optoelectronic applications based on electrically controllable atomically-thin semiconductors.

9.
Small ; : e2402567, 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39132749

ABSTRACT

The photosynaptic transistor stands as a promising contender for overcoming the von Neumann bottleneck in the realm of photo-communication. In this context, photonic synaptic transistors is developed through a straightforward solution process, employing an organic semiconducting polymer with pendant-naphthalene-containing side chains (PDPPNA) in combination with ligand-density-engineered CsPbBr3 perovskite quantum dots (PQDs). This fabrication approach allows the devices to emulate fundamental synaptic behaviors, encompassing excitatory postsynaptic current, paired-pulse facilitation, the transition from short-to-long-term memory, and the concept of "learning experience." Notably, the phototransistor, incorporating the blend of the PDPPNA and CsPbBr3 PQDs washed with ethyl acetate, achieved an exceptional memory ratio of 104. Simultaneously, the same device exhibited an impressive paired-pulse facilitation ratio of 223% at a moderate operating voltage of -4 V and an extraordinarily low energy consumption of 0.215 aJ at an ultralow operating voltage of -0.1 mV. Consequently, these low-voltage synaptic devices, constructed with a pendant side-chain engineering of organic semiconductors and a ligand density engineering of PQDs through a simple fabrication process, exhibit substantial potential for replicating the visual memory capabilities of the human brain.

10.
Clin Transl Sci ; 17(8): e70011, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39169685

ABSTRACT

Conventional dendritic cells subtype 1 (cDC1) play a vital role in the priming and expansion of tumor-specific CD8+ T cells and their recruitment to tumor microenvironment. However, cDC1s are often underrepresented in the microenvironment. Systemic administration of Fms-like tyrosine kinase 3 ligand, a hematopoietic growth factor that binds to FLT3 on myeloid and lymphoid progenitor cells, leads to cDC1 expansion in the periphery and recruitment into the microenvironment. FLT3 pathway stimulation using GS-3583, a novel FLT3 agonistic Fc fusion protein, has the potential to promote T-cell mediated antitumor activity. This was a first-in-human, placebo-controlled study of GS-3583 in healthy participants to evaluate the safety, pharmacokinetics (PK), and pharmacodynamic (PD) of escalating single doses (75-2000 µg) of GS-3583. Each dose cohort enrolled 8-12 healthy participants who received GS-3583 or placebo as single IV infusion at 3:1 ratio. As part of the PD evaluation, the changes in the number of cDC1 cells were investigated. GS-3583 was well-tolerated in healthy participants up to the highest evaluated dose (2000 µg). There have been no serious or grade III or higher adverse events. PK analysis suggested a dose-dependent increase in GS-3583 exposure with target-mediated disposition characteristics at low doses. PD analysis shows that administration of GS-3583 resulted in transient, dose-dependent increases in cDC1 cells that returned to baseline within 3 weeks of drug administration. The pharmacokinetics and pharmacodynamics of GS-3583 following single dosing were characterized in this study which enabled subsequent phase Ib assessments in patients with advanced solid tumors.


Subject(s)
Healthy Volunteers , Immunoglobulin Fc Fragments , Recombinant Fusion Proteins , fms-Like Tyrosine Kinase 3 , Humans , Adult , Male , Female , Middle Aged , Recombinant Fusion Proteins/pharmacokinetics , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/adverse effects , Recombinant Fusion Proteins/pharmacology , fms-Like Tyrosine Kinase 3/antagonists & inhibitors , Young Adult , Immunoglobulin Fc Fragments/administration & dosage , Immunoglobulin Fc Fragments/pharmacology , Immunoglobulin Fc Fragments/adverse effects , Dose-Response Relationship, Drug , Dendritic Cells/drug effects , Dendritic Cells/immunology , Double-Blind Method , Infusions, Intravenous
11.
Geriatr Nurs ; 60: 1-4, 2024 Aug 29.
Article in English | MEDLINE | ID: mdl-39214037

ABSTRACT

OBJECTIVES: To establish reference values for SPPB score as well as test performances among Taiwanese community-dwelling older adults. METHODS: Participants included 847 older adults. The total scores and three subtest scores for the SPPB and the registered time to complete the walk and five-repetition sit-to-stand (STS) tests were determined and compared between sex and age (65-74, 75-84, and ≥85 years) groups. RESULTS: The mean SPPB total score was 10.9 in women and 10.5 in men. SPPB scores did not differ by sex, regardless of age group. However, the walk test (p = .030) and STS test (p = .008) timings were longer for men than for women in the 65-74-year-old group. The ≥85-year-old men achieved a lower balance score than did the 65-74-year-old men (p = .027). CONCLUSIONS: Population-specific SPPB reference values contribute to assessments of physical function and facilitate cross-cultural comparisons of physical performance.

13.
Food Chem ; 459: 140336, 2024 Nov 30.
Article in English | MEDLINE | ID: mdl-39003859

ABSTRACT

The cell membrane, consisting of a phospholipid bilayer, is an important defense system of lactic acid bacteria (LAB) against adverse conditions. However, this membrane gets damaged during the process of spray drying of LAB into powder. In this study, two strains of Lactobacillus bulgaricus L9-7 and L4-2-12 with significantly different survival rates of about 22.49% and 0.43% after spray drying were explored at the cell membrane level. A total of 65 significantly different lipid species were screened from the cell membranes of two strains, with cardiolipin (CL) 15:1_22:6_24:0_28:0 being the crucial lipid species affecting membrane resistance. Finally, the KEGG enrichment analysis revealed that glycerophospholipid metabolism was the most predominant pathway, and eleven lipid species were annotated, including CL. Overall, this paper provides valuable insights into enhancing the heat tolerance of LAB.


Subject(s)
Lactobacillus delbrueckii , Lipidomics , Membrane Lipids , Lactobacillus delbrueckii/metabolism , Lactobacillus delbrueckii/chemistry , Membrane Lipids/chemistry , Membrane Lipids/metabolism , Spray Drying , Microbial Viability , Cell Membrane/chemistry , Cell Membrane/metabolism
14.
Adv Mater ; 36(35): e2405433, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39007283

ABSTRACT

Collective excitations including plasmons, magnons, and layer-breathing vibration modes emerge at an ultralow frequency (<1 THz) and are crucial for understanding van der Waals materials. Strain at the nanoscale can drastically change the property of van der Waals materials and create localized states like quantum emitters. However, it remains unclear how nanoscale strain changes collective excitations. Herein, ultralow-frequency tip-enhanced Raman spectroscopy (TERS) with sub-10 nm resolution under ambient conditions is developed to explore the localized collective excitation on monolayer semiconductors with nanoscale strains. A new vibrational mode is discovered at around 12 cm-1 (0.36 THz) on monolayer MoSe2 nanobubbles and it is identified as the radial breathing mode (RBM) of the curved monolayer. The correlation is determined between the RBM frequency and the strain by simultaneously performing deterministic nanoindentation and TERS measurement on monolayer MoSe2. The generality of the RBM in nanoscale curved monolayer WSe2 and bilayer MoSe2 is demonstrated. Using the RBM frequency, the strain of the monolayer MoSe2 on the nanoscale can be mapped. Such an ultralow-frequency vibration from curved van der Waals materials provides a new approach to study nanoscale strains and points to more localized collective excitations to be discovered at the nanoscale.

15.
Chin J Integr Med ; 30(9): 780-787, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39046647

ABSTRACT

OBJECTIVE: To assess the efficacy and safety of Sanjie Analgesic Capsule (SAC) in Chinese patients with endometriosis-associated pain. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled trial conducted at 15 centers between November 2013 and July 2017 in China. Eligible 323 patients with endometriosis were randomized at a 3:1 ratio to the SAC group (241 cases) and placebo group (82 cases) by stratified block randomization. Patients in the SAC or placebo groups were given SAC or placebo 1.6 g 3 times per day, orally, respectively since the first day of menstruation for 3 consecutive menstrual cycles. The primary endpoint was clinical response to dysmenorrhea evaluated using a 10-point Visual Analogue Scale at 3 and 6 months. The secondary endpoint was the pain score evaluated by VAS (chronic pelvic pain, defecation pain, and dyspareunia) at 3 and 6 months, and the pain recurrence rate at 6 months. Adverse events (AEs) were recorded during the study. RESULTS: A total of 241 women were included in the SAC group, and 82 were in the placebo group. Among these women, 217 (90.0%) and 71 (86.6%) completed the intervention, respectively. At 3 months, overall response rate (ORR) was significantly higher in women administered SAC (80.1%) compared with those who received a placebo (30.5%, P<0.01). Six months after treatment, the ORR for dysmenorrhea was 62.7% in the SAC group and 31.7% in the placebo group (P<0.01). Chronic pelvic pain and defecation pain were significantly improved by SAC compared with placebo (both P<0.05). The incidence rates of total AEs events in the SAC and placebo groups were 6.6% and 9.8%, respectively, and no significant difference was shown between the two groups (P=0.339). CONCLUSION: SAC is well-tolerated and may improve dysmenorrhea in women with endometriosis-associated pain. (Trial registration: ClinicalTrials.gov, No. NCT02031523).


Subject(s)
Analgesics , Capsules , Drugs, Chinese Herbal , Endometriosis , Humans , Female , Endometriosis/drug therapy , Endometriosis/complications , Double-Blind Method , Adult , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/adverse effects , Analgesics/therapeutic use , Analgesics/adverse effects , Treatment Outcome , Dysmenorrhea/drug therapy , Pain/drug therapy , Pain/etiology , Pelvic Pain/drug therapy , Pelvic Pain/etiology , Pain Measurement , Young Adult , Placebos
16.
Life (Basel) ; 14(7)2024 Jul 09.
Article in English | MEDLINE | ID: mdl-39063612

ABSTRACT

The study aimed to validate a newly developed postoperative stability score for evaluating clinical follow-up in elderly patients with low-energy hip fractures. From 1 January 2020 to 31 December 2021, we enrolled patients aged over 65 who underwent cephalomedullary nail fixation using proximal femoral nail antirotation II (PFNAII) and had at least 6 months of follow-up; excluding multiple fractures, pathological fractures, and periprosthetic fractures. We collected general patient data. Parameters such as TAD, Parker's ratio (AP and lateral), and the new postoperative stability score were recorded. A loss of reduction was defined using the decline in the Chang reduction quality criteria (CRQC) score within one month. Among the 108 enrolled patients, 23 (21.3%) experienced a loss of reduction, with a mean age of 82.1 years and a mean follow-up time of 7.4 months. Univariate analysis showed no significant association between loss of reduction and general data. However, the new postoperative stability score correlated significantly with loss of reduction (mean scores: 6.68 vs. 4.83, p = 0.045). Multivariate analysis confirmed this association (odds ratio: 0.076, 95% confidence interval: 0.022-0.263, p < 0.05). The newly developed postoperative stability score, incorporating surgical technique assessment, improves prediction accuracy for loss of reduction in elderly intertrochanteric fracture (ITF) patients.

17.
J Anim Sci ; 1022024 Jan 03.
Article in English | MEDLINE | ID: mdl-38995099

ABSTRACT

The negative effects of heat stress on swine reproduction have been well documented and the recent global warming trend caused by climate change is leading to more days with high temperatures every year. This has caused a reduction in litter trait performance of Landrace sows in Taiwan, a country extending across tropical and subtropical oceanic zones. Therefore, this study developed a modified model to determine which stages of pregnancy, before, early, middle, and late, had the largest impacts of heat stress on litter traits. A reaction norm model (RNM) was used to identify sows with high resilience to heat stress for litter traits followed by analysis of the modified model. Data from Landrace sows were collected from 2 farms in Taiwan between 2008 and 2021. A total of 11,059 records were collected for total number born (TNB), number born alive (NBA), and stillborn rate (STBR). The results showed that the heritabilities of TNB, NBA, and STBR were 0.170, 0.115, and 0.077, respectively. These results were similar between the conventional model and the modified model. In the modified model, the before and early stages of sow pregnancy were the significant periods for TNB and NBA (P < 0.05), while the early and middle stages were significant for STBR (P < 0.05). According to the RNM results, the heritability estimates for TNB, NBA, and STBR were 0.23 to 0.11, 0.18 to 0.08, and 0.10 to 0.04, respectively, showing a decrease from low temperature-humidity index (THI) to high THI. The minimum genetic correlations between the highest and the lowest THI for TNB, NBA, and STBR were 0.85, 0.64, and 0.80, respectively. The results of the RNM for breeding value showed re-ranking across THI values. In conclusion, similar results were obtained for heritability when the model was modified for heat stress estimation. Yet re-ranking of breeding values across THI could help farmers to select not only for improved litter trait performance but also for heat stress resilience of Landrace sows in Taiwan.


Heat stress caused by climate change is a challenge for the pig industry, especially in countries located in tropical and subtropical zones, such as Taiwan. It can adversely affect litter traits, leading to less pork production and higher economic losses to farms. Therefore, identifying sows with the potential to tolerate high heat with high humid condition is an important task for the pig industry. This article proposes a reaction norm model to determine the trend in breeding value across temperature and humidity index values and its implications for litter traits of sows. Our results indicate that litter traits can be used to select sows with high heat tolerance.


Subject(s)
Genotype , Animals , Female , Taiwan , Pregnancy , Swine/genetics , Swine/physiology , Litter Size/genetics , Gene-Environment Interaction , Reproduction/genetics , Heat-Shock Response/genetics
18.
Ann Neurol ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38979912

ABSTRACT

OBJECTIVE: Most paroxysmal kinesigenic dyskinesia (PKD) cases are hereditary, yet approximately 60% of patients remain genetically undiagnosed. We undertook the present study to uncover the genetic basis for undiagnosed PKD patients. METHODS: Whole-exome sequencing was performed for 106 PRRT2-negative PKD probands. The functional impact of the genetic variants was investigated in HEK293T cells and Drosophila. RESULTS: Heterozygous variants in KCNJ10 were identified in 11 individuals from 8 unrelated families, which accounted for 7.5% (8/106) of the PRRT2-negative probands. Both co-segregation of the identified variants and the significantly higher frequency of rare KCNJ10 variants in PKD cases supported impacts from the detected KCNJ10 heterozygous variants on PKD pathogenesis. Moreover, a KCNJ10 mutation-carrying father from a typical EAST/SeSAME family was identified as a PKD patient. All patients manifested dystonia attacks triggered by sudden movement with a short episodic duration. Patch-clamp recordings in HEK293T cells revealed apparent reductions in K+ currents of the patient-derived variants, indicating a loss-of-function. In Drosophila, milder hyperexcitability phenotypes were observed in heterozygous Irk2 knock-in flies compared to homozygotes, supporting haploinsufficiency as the mechanism for the detected heterozygous variants. Electrophysiological recordings showed that excitatory neurons in Irk2 haploinsufficiency flies exhibited increased excitability, and glia-specific complementation with human Kir4.1 rescued the Irk2 mutant phenotypes. INTERPRETATION: Our study established haploinsufficiency resulting from heterozygous variants in KCNJ10 can be understood as a previously unrecognized genetic cause for PKD and provided evidence of glial involvement in the pathophysiology of PKD. ANN NEUROL 2024.

19.
World J Clin Cases ; 12(21): 4762-4769, 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39070816

ABSTRACT

BACKGROUND: Retroperitoneal leiomyomas (RLs) are rare benign tumours that can occur in the pelvic and/or abdominal parietal retroperitoneum. Once torsion occurs, it causes acute abdominal pain and can even lead to serious consequences such as gangrene, peritonitis, haemoperitoneum and shock if not identified and treated promptly. Therefore, a better understanding of the characteristics of RL torsion is needed. Here, we present a case of acute pedicle torsion of an RL in the posterior peritoneum followed by a literature review. CASE SUMMARY: Herein, we report the case of a 42-year-old woman with RL torsion. The patient visited our hospital complaining of lower abdominal pain for 6 d. Pelvic examination revealed a tender mass superior to the uterus. Pelvic magnetic resonance imaging (MRI) revealed an anterior uterine mass, multiple uterine fibroids and slight pelvic effusion. MRI suggested the possibility of a subserosal myoma of the anterior uterine wall with degeneration. Intraoperative exploration revealed a 10 cm pedunculated mass arising from the posterior peritoneum, with the pedicle torsed two times. Pathological examination confirmed a torsed RL. CONCLUSION: In the case of a pelvic mass complicated with acute abdomen, the possibility of torsion should be considered.

20.
J Agric Food Chem ; 72(30): 17041-17050, 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39024493

ABSTRACT

Plasmin-induced protein hydrolysis significantly compromises the stability of ultrahigh-temperature (UHT) milk. ß-Lactoglobulin (ß-Lg) was observed to inhibit plasmin activity, suggesting that there were active sites as plasmin inhibitors in ß-Lg. Herein, plasmin inhibitory peptides were explored from ß-Lg using experimental and computational techniques. The results revealed that increased denaturation of ß-Lg enhanced its affinity for plasmin, leading to a stronger inhibition of plasmin activity. Molecular dynamics simulations indicated that electrostatic and van der Waals forces were the primary binding forces in the ß-Lg/plasmin complex. Denatured ß-Lg increased hydrogen bonding and reduced the binding energy with plasmin. The sites of plasmin bound to ß-Lg were His624, Asp667, and Ser762. Four plasmin inhibitory peptides, QTMKGLDI, EKTKIPAV, TDYKKYLL, and CLVRTPEV, were identified from ß-Lg based on binding sites. These peptides effectively inhibited plasmin activity and enhanced the UHT milk stability. This study provided new insights into the development of novel plasmin inhibitors to improve the stability of UHT milk.


Subject(s)
Fibrinolysin , Lactoglobulins , Milk , Lactoglobulins/chemistry , Animals , Milk/chemistry , Fibrinolysin/chemistry , Fibrinolysin/metabolism , Fibrinolysin/antagonists & inhibitors , Cattle , Hot Temperature , Food Storage , Molecular Dynamics Simulation , Antifibrinolytic Agents/chemistry , Peptides/chemistry , Peptides/pharmacology
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