Heart rate variability biofeedback enhances cognitive, motor, psychological, and autonomic functions in post-stroke rehabilitation.

Post-stroke patients often experience psychological distress and autonomic nervous system (ANS) dysregulation, impacting their well-being. This study evaluated the effectiveness of heart rate variability (HRV) biofeedback on cognitive, motor, psychological, and ANS functions in sixty-two ischemic stroke patients (43 males, mean age = 60.1) at a Medical Center in southern Taiwan. To prevent interaction, we allocated patients to the HRV biofeedback or control (usual care) group based on their assigned rehabilitation days, with 31 patients in each group. Assessments conducted at baseline, three, and six months included the Montreal Cognitive Assessment (MoCA), Fugl-Meyer Assessment for Upper Extremities (FMA-UE), Perceived Stress Scale, Hospital Anxiety and Depression Scales (HADS), and HRV indices. Mixed-effect models were used to analyze Group by Time interactions. The results revealed significant interactions across all functions. At 3 months, significant improvements in the HRV biofeedback group were observed only in MoCA, FMA-UE, and HADS-depression scores compared to the control group. By 6 months, all measured outcomes demonstrated significant improvements in the biofeedback group relative to the control group. These results suggest that HRV biofeedback may be an effective complementary intervention in post-stroke rehabilitation, warranting further validation.

The CCR6-CCL20 axis promotes regulatory T cell glycolysis and immunosuppression in tumors.

Regulatory T cells (Tregs) are important players in the tumor microenvironment. However, the mechanisms behind their immunosuppressive effects are poorly understood. We found that CCR6-CCL20 activity in tumor-infiltrating Tregs is associated with greater glycolytic activity and ablation of Ccr6 reduced glycolysis and lactic acid production while increasing compensatory glutamine metabolism. Immunosuppressive activity towards CD8+ T cells was abrogated in Ccr6-/- Tregs due to reduction in activation-induced glycolysis. Furthermore, Ccr6-/- mice exhibited improved survival across multiple tumor models compared to wildtype mice, and Treg and CD8+ T-cell depletion abrogated the improvement. In addition, Ccr6 ablation further promoted the efficacy of anti-PD-1 therapy in a preclinical glioma model. Follow-up knockdown of Ccl20 with siRNA also demonstrated improvement in antitumor efficacy. Our results unveil CCR6 as a marker and regulator of Treg-induced immunosuppression and identify approaches to target the metabolic determinants of Treg immunosuppressive activity.

Comparing the stability and reproducibility of brain-behavior relationships found using canonical correlation analysis and partial least squares within the ABCD sample.

Canonical correlation analysis (CCA) and partial least squares correlation (PLS) detect linear associations between two data matrices by computing latent variables (LVs) having maximal correlation (CCA) or covariance (PLS). This study compared the similarity and generalizability of CCA- and PLS-derived brain-behavior relationships. Data were accessed from the baseline Adolescent Brain Cognitive Development (ABCD) dataset (N > 9,000, 9-11 years). The brain matrix consisted of cortical thickness estimates from the Desikan-Killiany atlas. Two phenotypic scales were examined separately as the behavioral matrix; the Child Behavioral Checklist (CBCL) subscale scores and NIH Toolbox performance scores. Resampling methods were used to assess significance and generalizability of LVs. LV1 for the CBCL brain relationships was found to be significant, yet not consistently stable or reproducible, across CCA and PLS models (singular value: CCA = .13, PLS = .39, p < .001). LV1 for the NIH brain relationships showed similar relationships between CCA and PLS and was found to be stable and reproducible (singular value: CCA = .21, PLS = .43, p < .001). The current study suggests that stability and reproducibility of brain-behavior relationships identified by CCA and PLS are influenced by the statistical characteristics of the phenotypic measure used when applied to a large population-based pediatric sample.

Clinical neuroscience research is going through a translational crisis largely due to the challenges of producing meaningful and generalizable results. Two critical limitations within clinical neuroscience research are the use of univariate statistics and between-study methodological variation. Univariate statistics may not be sensitive enough to detect complex relationships between several variables, and methodological variation poses challenges to the generalizability of the results. We compared two widely used multivariate statistical approaches, canonical correlations analysis (CCA) and partial least squares correlation (PLS), to determine the generalizability and stability of their solutions. We show that the properties of the measures inputted into the analysis likely play a more substantial role in the generalizability and stability of results compared to the specific approach applied (i.e., CCA or PLS).

Transdiagnostic Neurobiology of Social Cognition and Individual Variability as Measured by Fractional Amplitude of Low-Frequency Fluctuation in Schizophrenia and Autism Spectrum Disorders.

Fractional amplitude of low-frequency fluctuation (fALFF) is a validated measure of resting-state spontaneous brain activity. Previous fALFF findings in autism and schizophrenia spectrum disorders (ASDs and SSDs) have been highly heterogeneous. We aimed to use fALFF in a large sample of typically developing control (TDC), ASD and SSD participants to explore group differences and relationships with inter-individual variability of fALFF maps and social cognition. fALFF from 495 participants (185 TDC, 68 ASD, and 242 SSD) was computed using functional magnetic resonance imaging as signal power within two frequency bands (i.e., slow-4 and slow-5), normalized by the power in the remaining frequency spectrum. Permutation analysis of linear models was employed to investigate the relationship of fALFF with diagnostic groups, higher-level social cognition, and lower-level social cognition. Each participant's average distance of fALFF map to all others was defined as a variability score, with higher scores indicating less typical maps. Lower fALFF in the visual and higher fALFF in the frontal regions were found in both SSD and ASD participants compared with TDCs. Limited differences were observed between ASD and SSD participants in the cuneus regions only. Associations between slow-4 fALFF and higher-level social cognitive scores across the whole sample were observed in the lateral occipitotemporal and temporoparietal junction. Individual variability within the ASD and SSD groups was also significantly higher compared with TDC. Similar patterns of fALFF and individual variability in ASD and SSD suggest some common neurobiological deficits across these related heterogeneous conditions.

Inter-Relations between Dietary Patterns and Glycemic Control-Related Biomarkers on Risk of Retinopathy in Type 2 Diabetes.

Diabetic retinopathy (DR), which can cause vision loss, may progress faster with poor glycemic control and oxidative stress. This study aims to examine how dietary patterns and glycemic control biomarkers relate to retinopathy risk in type 2 diabetes patients. In this study, we enrolled diabetic patients with retinopathy (DR) (n = 136) and without retinopathy (no DR) (n = 466) from a cohort of participants in the "Blood Pressure Control to Reduce the Risk of Type 2 Diabetic Nephropathy Study". Hemoglobin A1c (HbA1c) and malondialdehyde were defined as elevated when their levels reached ≥8.5% and ≥2/3 (16.2 µm), respectively. Dietary data were collected by a food frequency questionnaire. Dietary patterns were identified by factor analysis. Elevated HbA1c was significantly correlated with increased risk of DR (OR: 2.12, 95% CI: 1.14-3.93, p = 0.017). In subjects with a high animal protein and processed food dietary pattern (≥highest tertile score) or a low vegetable intake pattern (

The First Domesticated 'Cheongju Sorori Rice' Excavated in Korea.

Archaeological excavations led by Yung-jo Lee and Jong-yoon Woo were carried out twice at the Sorori paleolithic site, Cheongju, in the Republic of Korea, at the upper stream of the Geumgang river, the Miho riverside. A total of 127 rice seeds were excavated, including 18 ancient rice and 109 Quasi-rice, in 1998 and 2001. At the first excavation, eleven short japonica-type ancient rice and one slender smooth ancient rice with two kinds of Quasi-rice were excavated. The average length of the 11 short rice grains obtained from the first and second excavation was 7.19 mm and the average width was 3.08 mm, respectively. The Quasi-rice are apparently different from the rice and do not have bi-peak protuberances on their glume surface. At the second excavation, six short ancient rice chaffs and some Quasi-rice 2 were found. These short-grained ancient rice were comparable to the ancient rice that were excavated at the Illsan Neolithic site. Geologists and radiologists confirmed that the peat layer in which the rice found was older than 15,000 years. In this study, the morphological characteristics, crushing, and DNA band patterns related to the genetic polymorphism of rice grains in Cheongju Sorori were compared and analyzed for genetic similarities and differences with wild rice, weed rice, and modern rice. The morphological, ecological, and physiological variations in rice grains excavated from the Sorori site were presumed to denote the origin of rice domestication in Korea. It is also suggested that the results of the DNA sequencing of excavated rice are very important clues in estimating the origin of the early domestication of rice.

Assessment of hepatitis B virus relapse in cancer patients receiving chemotherapy with prophylactic nucleos(t)ide analogues: Implications for overall mortality.

BACKGROUND AND AIMS: We aimed to explore the risk factors associated with virological and clinical relapse, as well as their impact on overall mortality, in hepatitis B virus (HBV)-infected patients receiving nucleos(t)ide analogues (NUCs) therapy prior to chemotherapy initiation. METHODS: From 2010 to 2020, we conducted a prospective cohort study involving patients with HBV infection undergoing cytotoxic chemotherapy. We utilized the Kaplan-Meier method and Cox proportional hazard regression models to assess risk factors. RESULTS: We observed that TDF or TAF (HR: 2.16, 95% CI 1.06-4.41; p = .034), anthracycline (HR: 1.73, 95% CI 1.10-2.73; p = .018), baseline HBV DNA (HR: 1.55, 95% CI 1.33-1.81; p < .001) and end-of-treatment HBsAg titre >100 IU/mL (HR: 7.81, 95% CI 1.94-31.51; p = .004) were associated with increased risk of virological relapse. Additionally, TDF or TAF (HR: 4.91, 95% CI 1.45-16.64; p = .011), baseline HBV DNA (HR: 1.48, 95% CI 1.10-1.99; p = .009) and end-of-treatment HBsAg titre >100 IU/mL (HR: 6.09, 95% CI .95-38.87; p = .056) were associated with increased risk of clinical relapse. Furthermore, we found that virological relapse (HR: 3.32, 95% CI 1.33-8.32; p = .010) and clinical relapse (HR: 3.59, 95% CI 1.47-8.80; p = .005) significantly correlated with all-cause mortality in HBV patients receiving cytotoxic chemotherapy with prophylactic NUCs therapy. CONCLUSIONS: The risk of virological and clinical relapse was linked to baseline HBV DNA, end-of-treatment HBsAg levels and TDF or TAF for prophylaxis; additionally, experiencing relapse heightens the risk of all-cause mortality. Further research is warranted to explore potential strategies for preventing virological and clinical relapse in high-risk patients.

E3 ligase RNF2 inhibits porcine circovirus type 3 replication by targeting its capsid protein for ubiquitination-dependent degradation.

Porcine circovirus type 3 (PCV3) is closely associated with various diseases, such as the porcine dermatitis, nephropathy syndrome, and multisystemic clinicopathological diseases. PCV3-associated diseases are increasingly recognized as severe diseases in the global swine industry. Ring finger protein 2 (RNF2), an E3 ubiquitin ligase exclusively located in the nucleus, contributes to various biological processes. This ligase interacts with the PCV3 Cap. However, its role in PCV3 replication remains unclear. This study confirmed that the nuclear localization signal domain of the Cap and the RNF2 N-terminal RING domain facilitate the interaction between the Cap and RNF2. Furthermore, RNF2 promoted the binding of K48-linked polyubiquitination chains to lysine at positions 139 and 140 (K139 and K140) of the PCV3 Cap, thereby degrading the Cap. RNF2 knockdown and overexpression increased or decreased PCV3 replication, respectively. Moreover, the RING domain-deleted RNF2 mutant eliminated the RNF2-induced degradation of the PCV3 Cap and RNF2-mediated inhibition of viral replication. This indicates that both processes were associated with its E3 ligase activity. Our findings demonstrate that RNF2 can interact with and degrade the PCV3 Cap via its N-terminal RING domain in a ubiquitination-dependent manner, thereby inhibiting PCV3 replication.IMPORTANCEPorcine circovirus type 3 is a recently described pathogen that is prevalent worldwide, causing substantial economic losses to the swine industry. However, the mechanisms through which host proteins regulate its replication remain unclear. Here, we demonstrate that ring finger protein 2 inhibits porcine circovirus type 3 replication by interacting with and degrading the Cap of this pathogen in a ubiquitination-dependent manner, requiring its N-terminal RING domain. Ring finger protein 2-mediated degradation of the Cap relies on its E3 ligase activity and the simultaneous existence of K139 and K140 within the Cap. These findings reveal the mechanism by which this protein interacts with and degrades the Cap to inhibit porcine circovirus type 3 replication. This consequently provides novel insights into porcine circovirus type 3 pathogenesis and facilitates the development of preventative measures against this pathogen.

Data Independent Acquisition Mass Spectrometry Enhanced Personalized Glycosylation Profiling of Haptoglobin in Hepatocellular Carcinoma.

Aberrant glycosylation has gained significant interest for biomarker discovery. However, low detectability, complex glycan structures, and heterogeneity present challenges in glycoprotein assay development. Using haptoglobin (Hp) as a model, we developed an integrated platform combining functionalized magnetic nanoparticles and zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) for highly specific glycopeptide enrichment, followed by a data-independent acquisition (DIA) strategy to establish a deep cancer-specific Hp-glycosylation profile in hepatitis B virus (HBV, n = 5) and hepatocellular carcinoma (HCC, n = 5) patients. The DIA strategy established one of the deepest Hp-glycosylation landscapes (1029 glycopeptides, 130 glycans) across serum samples, including 54 glycopeptides exclusively detected in HCC patients. Additionally, single-shot DIA searches against a DIA-based spectral library outperformed the DDA approach by 2-3-fold glycopeptide coverage across patients. Among the four N-glycan sites on Hp (N-184, N-207, N-211, N-241), the total glycan type distribution revealed significantly enhanced detection of combined fucosylated-sialylated glycans, which were the most dominant glycoforms identified in HCC patients. Quantitation analysis revealed 48 glycopeptides significantly enriched in HCC (p < 0.05), including a hybrid monosialylated triantennary glycopeptide on the N-184 site with nearly none-to-all elevation to differentiate HCC from the HBV group (HCC/HBV ratio: 2462 ± 766, p < 0.05). In summary, DIA-MS presents an unbiased and comprehensive alternative for targeted glycoproteomics to guide discovery and validation of glyco-biomarkers.

A Rapid One-Pot Workflow for Sensitive Microscale Phosphoproteomics.

Compared to advancements in single-cell proteomics, phosphoproteomics sensitivity has lagged behind due to low abundance, complex sample preparation, and substantial sample input requirements. We present a simple and rapid one-pot phosphoproteomics workflow (SOP-Phos) integrated with data-independent acquisition mass spectrometry (DIA-MS) for microscale phosphoproteomic analysis. SOP-Phos adapts sodium deoxycholate based one-step lysis, reduction/alkylation, direct trypsinization, and phosphopeptide enrichment by TiO2 beads in a single-tube format. By reducing surface adsorptive losses via utilizing n-dodecyl ß-d-maltoside precoated tubes and shortening the digestion time, SOP-Phos is completed within 3-4 h with a 1.4-fold higher identification coverage. SOP-Phos coupled with DIA demonstrated >90% specificity, enhanced sensitivity, lower missing values (<1%), and improved reproducibility (8%-10% CV). With a sample size-comparable spectral library, SOP-Phos-DIA identified 33,787 ± 670 to 22,070 ± 861 phosphopeptides from 5 to 0.5 µg cell lysate and 30,433 ± 284 to 6,548 ± 21 phosphopeptides from 50,000 to 2,500 cells. Such sensitivity enabled mapping key lung cancer signaling sites, such as EGFR autophosphorylation sites Y1197/Y1172 and drug targets. The feasibility of SOP-Phos-DIA was demonstrated on EGFR-TKI sensitive and resistant cells, revealing the interplay of multipathway Hippo-EGFR-ERBB signaling cascades underlying the mechanistic insight into EGFR-TKI resistance. Overall, SOP-Phos-DIA is an efficient and robust protocol that can be easily adapted in the community for microscale phosphoproteomic analysis.

Dynamic change of MASLD in chronic hepatitis C patients after viral eradication: A nationwide registry study in Taiwan.

Background/Aims: Steatotic liver disease (SLD) is a common manifestation in chronic hepatitis C (CHC). Metabolic alterations in CHC are associated with metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to elucidate whether hepatitis C virus (HCV) eradication mitigates MASLD occurrence or resolution. Methods: We enrolled 5,840 CHC patients whose HCV was eradicated by direct-acting antivirals in a nationwide HCV registry. MASLD and the associated cardiometabolic risk factors (CMRFs) were evaluated at baseline and 6 months after HCV cure. Results: There were 2,147 (36.8%) patients with SLD, and 1,986 (34.0%) of them met the MASLD criteria before treatment. After treatment, HbA1C (6.0% vs. 5.9%, P<0.001) and BMI (24.8 kg/m2 vs. 24.7 kg/m2, P<0.001) decreased, whereas HDL-C (49.1 mg/dL vs. 51.9 mg/dL, P<0.001) and triglycerides (102.8 mg/dL vs. 111.9 mg/dL, P<0.001) increased significantly. The proportion of patients with SLD was 37.5% after HCV eradication, which did not change significantly compared with the pretreatment status. The percentage of the patients who had post-treatment MASLD was 34.8%, which did not differ significantly from the pretreatment status (P=0.17). Body mass index (BMI) (odds ratio [OR]/95% confidence intervals [CI]: 0.89/0.85-0.92, P<0.001) was the only factor associated with MASLD resolution. In contrast, unfavorable CMRFs, including BMI (OR/CI: 1.10/1.06-1.14, P<0.001) and HbA1c (OR/CI: 1.19/1.04-1.35, P=0.01), were independently associated with MASLD development after HCV cure. Conclusions: HCV eradication mitigates MASLD in CHC patients. CMRF surveillance is mandatory for CHC patients with metabolic alterations, which are altered after HCV eradication and predict the evolution of MASLD.

The efficacy of early office hysteroscopy in preventing intrauterine adhesions after abortion: a randomized controlled trial.

BACKGROUND: Intrauterine adhesions (IUA) are a challenging clinical problem in reproductive infertility. The most common causes are intrauterine surgery and abortions. We aimed to investigate whether early second-look office hysteroscopy can prevent IUA. METHODS: A single-center, prospective, two-armed, randomized controlled trial was designed to explore the efficacy of early office hysteroscopy after first-trimester induced abortion (suction dilatation and curettage [D&C]) and to further analyze fertility outcomes. Women aged 20-45 years undergoing suction D&C and desiring to conceive were recruited. Between October 2019 and September 2022, 66 women were enrolled, of whom 33 were allocated to group A (early hysteroscopy intervention). The women in intervention group A were planned to receive 2 times of hysteroscopies (early and late). In group B, women only underwent late (6 months post suction D&C) hysteroscopy. RESULTS: The primary outcome was the IUA rate assessed using office hysteroscopy 6 months after artificial abortion. Secondary outcomes included menstrual amount/durations and fertility outcomes. In intervention group A, 31 women underwent the first hysteroscopy examination, and 15 completed the second. In group B (late hysteroscopy intervention, 33 patients), 16 completed the hysteroscopic exam 6 months after an artificial abortion. Twenty-one women did not receive late hysteroscopy due to pregnancy. The IUA rate was 16.1% (5/31) at the first hysteroscopy in group A, and no IUA was detected during late hysteroscopy. Neither group showed statistically significant differences in the follow-up pregnancy and live birth rates. CONCLUSIONS: Early hysteroscopy following suction D&C can detect intrauterine lesions. IUA detected early by hysteroscopy can disappear on late examination and become insignificant for future pregnancies. Notably, the pregnancy outcomes showed a favorable trend in the early hysteroscopy group, but there were no statistically significant differences. TRIAL REGISTRATION: ClinicalTrials.gov , ID: NCT04166500. Registered on 2019-11-10. https://clinicaltrials.gov/ct2/show/NCT04166500 .

Cerebrospinal Fluid Proteome Map Reveals Molecular Signatures of Reversible Cerebral Vasoconstriction Syndrome.

Reversible cerebral vasoconstriction syndrome (RCVS) is a complex neurovascular disorder characterized by repetitive thunderclap headaches and reversible cerebral vasoconstriction. The pathophysiological mechanism of this mysterious syndrome remains underexplored and there is no clinically available molecular biomarker. To provide insight into the pathogenesis of RCVS, this study reported the first landscape of dysregulated proteome of cerebrospinal fluid (CSF) in patients with RCVS (n = 21) compared to the age- and sex-matched controls (n  = 20) using data-independent acquisition mass spectrometry. Protein-protein interaction and functional enrichment analysis were employed to construct functional protein networks using the RCVS proteome. An RCVS-CSF proteome library resource of 1054 proteins was established, which illuminated large groups of upregulated proteins enriched in the brain and blood-brain barrier (BBB). Personalized RCVS-CSF proteomic profiles from 17 RCVS patients and 20 controls reveal proteomic changes involving the complement system, adhesion molecules, and extracellular matrix, which may contribute to the disruption of BBB and dysregulation of neurovascular units. Moreover, an additional validation cohort validated a panel of biomarker candidates and a two-protein signature predicted by machine learning model to discriminate RCVS patients from controls with an area under the curve of 0.997. This study reveals the first RCVS proteome and a potential pathogenetic mechanism of BBB and neurovascular unit dysfunction. It also nominates potential biomarker candidates that are mechanistically plausible for RCVS, which may offer potential diagnostic and therapeutic opportunities beyond the clinical manifestations.

Genetic variation and evolutionary characteristics of Echovirus 11: new variant within genotype D5 associated with neonatal death found in China.

Echovirus 11 (E11) has gained attention owing to its association with severe neonatal infections. From 2018 to 2023, a surge in severe neonatal cases and fatalities linked to a novel variant of genotype D5 was documented in China, France, and Italy. However, the prevention and control of E11 variants have been hampered by limited background data on the virus circulation and genetic variance. Therefore, the present study investigated the circulating dynamics of E11 and the genetic variation and molecular evolution of genotype D5 through the collection of strains from the national acute flaccid paralysis (AFP) and hand, foot, and mouth disease (HFMD) surveillance system in China during 2000-2022 and genetic sequences published in the GenBank database. The results of this study revealed a prevalent dynamic of E11 circulation, with D5 being the predominant genotype worldwide. Further phylogenetic analysis of genotype D5 indicated that it could be subdivided into three important geographic clusters (D5-CHN1: 2014-2019, D5-CHN2: 2016-2022, and D5-EUR: 2022-2023). Additionally, variant-specific (144) amino acid mutation sites and positive-selection pressure sites (132, 262) were identified in the VP1 region. Cluster-specific recombination patterns were also identified, with CVB5, E6, and CVB4 as the major recombinant viruses. These findings provide a preliminary landscape of E11 circulation worldwide and basic scientific data for further study of the pathogenicity of E11 variants.

Increasing DNA damage sensitivity through corylin-mediated inhibition of homologous recombination.

BACKGROUND: DNA repair allows the survival of cancer cells. Therefore, the development of DNA repair inhibitors is a critical need for sensitizing cancers to chemoradiation. Sae2CtIP has specific functions in initiating DNA end resection, as well as coordinating cell cycle checkpoints, and it also greatly interacts with the DDR at different levels. RESULTS: In this study, we demonstrated that corylin, a potential sensitizer, causes deficiencies in DNA repair and DNA damage checkpoints in yeast cells. More specifically, corylin increases DNA damage sensitivity through the Sae2-dependent pathway and impairs the activation of Mec1-Ddc2, Rad53-p and γ-H2A. In breast cancer cells, corylin increases apoptosis and reduces proliferation following Dox treatment by inhibiting CtIP. Xenograft assays showed that treatment with corylin combined with Dox significantly reduced tumor growth in vivo. CONCLUSIONS: Our findings herein delineate the mechanisms of action of corylin in regulating DNA repair and indicate that corylin has potential long-term clinical utility as a DDR inhibitor.

Application of near-infrared spectroscopy to assess the effect of the cupping size on the spatial hemodynamic response from the area inside and outside the cup of the biceps.

Cupping therapy is a popular intervention for improving muscle recovery after exercise although clinical evidence is weak. Previous studies demonstrated that cupping therapy may improve microcirculation of the soft tissue to accelerate tissue healing. However, it is unclear whether the cupping size could affect the spatial hemodynamic response of the treated muscle. The objective of this study was to use 8-channel near-infrared spectroscopy to assess this clinical question by assessing the effect of 3 cupping sizes (35, 40, and 45 mm in inner diameter of the circular cup) under -300 mmHg for 5 min on the muscle hemodynamic response from the area inside and outside the cup, including oxyhemoglobin and deoxy-hemoglobin in 18 healthy adults. Two-way factorial design was used to assess the interaction between the cupping size (35, 40, and 45 mm) and the location (inside and outside the cup) and the main effects of the cupping size and the location. The two-way repeated measures ANOVA demonstrated an interaction between the cupping size and the location in deoxy-hemoglobin (P = 0.039) but no interaction in oxyhemoglobin (P = 0.100), and a main effect of the cup size (P = 0.001) and location (P = 0.023) factors in oxyhemoglobin. For the cupping size factor, the 45-mm cup resulted in a significant increase in oxyhemoglobin (5.738±0.760 µM) compared to the 40-mm (2.095±0.312 µM, P<0.001) and 35-mm (3.134±0.515 µM, P<0.01) cup. Our findings demonstrate that the cupping size and location factors affect the muscle hemodynamic response, and the use of multi-channel near-infrared spectroscopy may help understand benefits of cupping therapy on managing musculoskeletal impairment.

Comparative Study of the Impurity Effect on SnAgCu and SnZn Solder Joints with Electrodeposited Cu.

Sn-3Ag-0.5Cu (SAC305)- and Sn-9Zn-based alloys (Sn-Zn-X, X = Al, In) are lead-free solders used in the fabrication of solder joints with Cu metallization. Electroplating is a facile technology used to fabricate Cu metallization. However, the addition of functional additive molecules in the plating solution may result in impurity residues in the Cu electroplated layer, causing damage to the solder joints. This study investigates the impurity effect on solder joints constructed by joining various solder alloys to the Cu electroplated layers. Functional additives are formulated to fabricate high-impurity and low-impurity Cu electroplated samples. The as-joined solder joint samples are thermally aged at 120 °C and 170 °C to explore the interfacial reactions between solder alloys and Cu. The results show that the impurity effect on the interfacial reactions between SAC305 and Cu is significant. Voids are massively formed at the SAC305/Cu interface incorporated with a high impurity content, and the Cu6Sn5 intermetallic compound (IMC) grows at a faster rate. In contrast, the growth of the Cu5Zn8 IMC formed in the SnZn-based solder joints is not significantly influenced by the impurity content in the Cu electroplated layers. Voids are not observed in the SnZn-based solder joints regardless of the impurity content, indicative of an insignificant impurity effect. The discrepancy of the impurity effect is rationalized by the differences in the IMC formation and associated atomic interdiffusion in the SAC305- and SnZn-based solder joints.

Identification of Molecular Profile of Ear Fibroblasts Derived from Spindle-Transferred Holstein Cattle with Ooplasts from Taiwan Yellow Cattle under Heat Stress.

Global warming has a significant impact on the dairy farming industry, as heat stress causes reproductive endocrine imbalances and leads to substantial economic losses, particularly in tropical-subtropical regions. The Holstein breed, which is widely used for dairy production, is highly susceptible to heat stress, resulting in a dramatic reduction in milk production during hot seasons. However, previous studies have shown that cells of cows produced from reconstructed embryos containing cytoplasm (o) from Taiwan yellow cattle (Y) have improved thermotolerance despite their nuclei (n) being derived from heat-sensitive Holstein cattle (H). Using spindle transfer (ST) technology, we successfully produced ST-Yo-Hn cattle and proved that the thermotolerance of their ear fibroblasts is similar to that of Y and significantly better than that of H (p < 0.05). Despite these findings, the genes and molecules responsible for the different sensitivities of cells derived from ST-Yo-Hn and H cattle have not been extensively investigated. In the present study, ear fibroblasts from ST-Yo-Hn and H cattle were isolated, and differentially expressed protein and gene profiles were compared with or without heat stress (hs) (42 °C for 12 h). The results revealed that the relative protein expression levels of pro-apoptotic factors, including Caspase-3, -8, and -9, in the ear fibroblasts from the ST-Yo-Hn-hs group were significantly lower (p < 0.05) than those from the H-hs group. Conversely, the relative expression levels of anti-apoptotic factors, including GNA14 protein and the CRELD2 and PRKCQ genes, were significantly higher (p < 0.05) in the ear fibroblasts from the ST-Yo-Hn-hs group compared to those from the H-hs group. Analysis of oxidative phosphorylation-related factors revealed that the relative expression levels of the GPX1 gene and Complex-I, Complex-IV, CAT, and PGLS proteins were significantly higher (p < 0.05) in the ear fibroblasts from the ST-Yo-Hn-hs group compared to those from the H-hs group. Taken together, these findings suggest that ear fibroblasts from ST-Yo-Hn cattle have superior thermotolerance compared to those from H cattle due to their lower expression of pro-apoptotic factors and higher expression of oxidative phosphorylation and antioxidant factors. Moreover, this improved thermotolerance is attributed, at least partially, to the cytoplasm derived from more heat-tolerant Y cattle. Hence, using ST technology to produce more heat-tolerant H cattle containing Y cytoplasm could be a feasible approach to alleviate the negative impacts of heat stress on dairy cattle in tropical-subtropical regions.

Enhanced Proteomic Coverage in Tissue Microenvironment by Immune Cell Subtype Library-Assisted DIA-MS.

Immune cells that infiltrate the tumor microenvironment (TME) play crucial roles in shaping cancer development and influencing clinical outcomes and therapeutic responses. However, obtaining a comprehensive proteomic snapshot of tumor-infiltrating immunity in clinical specimens is often hindered by small sample amounts and a low proportion of immune infiltrating cells in the TME. To enable in-depth and highly sensitive profiling of microscale tissues, we established an immune cell-enriched library-assisted strategy for data-independent acquisition mass spectrometry (DIA-MS). Firstly, six immune cell subtype-specific spectral libraries were established from sorted cluster of differentiation markers, CD8+, CD4+ T lymphocytes, B lymphocytes, natural killer cells, dendritic cells, and macrophages in murine mesenteric lymph nodes (MLNs), covering 7815 protein groups with surface markers and immune cell-enriched proteins. The feasibility of microscale immune proteomic profiling was demonstrated on 1 µg tissue protein from the tumor of murine colorectal cancer (CRC) models using single-shot DIA; the immune cell-enriched library increased coverage to quantify 7419 proteins compared to directDIA analysis (6978 proteins). The enhancement enabled the mapping of 841 immune function-related proteins and exclusive identification of many low-abundance immune proteins, such as CD1D1, and CD244, demonstrating high sensitivity for immune landscape profiling. This approach was used to characterize the MLNs in CRC models, aiming to elucidate the mechanism underlying their involvement in cancer development within the TME. Even with a low percentage of immune cell infiltration (0.25-3%) in the tumor, our results illuminate downregulation in the adaptive immune signaling pathways (such as C-type lectin receptor signaling, and chemokine signaling), T cell receptor signaling, and Th1/Th2/Th17 cell differentiation, suggesting an immunosuppressive status in MLNs of CRC model. The DIA approach using the immune cell-enriched libraries showcased deep coverage and high sensitivity that can facilitate illumination of the immune proteomic landscape for microscale samples.