Deletion of protein kinase C θ attenuates hepatic ischemia/reperfusion injury and further elucidates its mechanism in pathophysiology.

Objectives: Hepatic ischemia-reperfusion (HIR) is a severe process in pathophysiology that occurs clinically in hepatectomy, and hepatic transplantations. The present study aimed to investigate the effect of PKC θ deletion against HIR injury and elucidate its mechanism in pathophysiology. Materials and Methods: HIR injury was induced in wild-type and PKC θ deletion mice treated with or without heme. The ALT and AST levels were determined to evaluate liver function. HIR injury was observed via histological examination. Oxidative stress and inflammatory response markers, and their signaling pathways were detected. Results: The study found that PKC θ knockout decreased serum AST and ALT levels when compared to the WT mice. Furthermore, heme treatment significantly reduced the ALT and AST levels of the PKC θ deletion mice compared with the untreated PKC θ deletion mice. PKC θ deletion markedly elevated superoxide dismutase activity in the liver tissue, reduced malondialdehyde content in the tissue, and the serum TNF-α and IL-6 levels compared with the WT mice. Heme treatment was observed to elevate the activity of SOD and reduced MDA content and serum of TNF-α and IL 6 in the PKC θ deletion animals. Meanwhile, heme treatment increased HO-1 and Nrf 2 protein expression, and reduced the levels of TLR4, phosphorylated NF-κB, and IKB-α. Conclusion: These findings suggested that PKC θ deletion ameliorates HIR, and heme treatment further improves HIR, which is related to regulation of PKC θ deletion on Nrf 2/HO-1 and TLR4/NF-κB/IKB α pathway.

Integrated landscape of plasma metabolism and proteome of patients with post-traumatic deep vein thrombosis.

Deep vein thrombosis (DVT) is a leading cause of morbidity and mortality after trauma. Here, we integrate plasma metabolomics and proteomics to evaluate the metabolic alterations and their function in up to 680 individuals with and without DVT after trauma (pt-DVT). We identify 28 metabolites and 2 clinical parameter clusters associated with pt-DVT. Then, we develop a panel of 9 metabolites (hexadecanedioic acid, pyruvic acid, L-Carnitine, serotonin, PE(P-18:1(11Z)/18:2(9Z,12Z)), 3-Hydroxycapric acid, 5,6-DHET, 3-Methoxybenzenepropanoic acid and pentanenitrile) that can predict pt-DVT with high performance, which can be verified in an independent cohort. Furthermore, the integration analysis of metabolomics and proteomics data indicates that the upregulation of glycolysis/gluconeogenesis-TCA cycle may promote thrombosis by regulating ROS levels in red blood cells, suggesting that interfering with this process might be potential therapeutic strategies for pt-DVT. Together, our study comprehensively delineates the metabolic and hematological dysregulations for pt-DVT, and provides potential biomarkers for early detection.

Physical activity, sedentary behavior, and risk of sepsis: a two-sample mendelian randomization study.

Objective: This investigation aimed to explore the potential causal relationship between physical activity, sedentary behavior and the risk of sepsis. Methods: Using a two-sample Mendelian randomization approach, this study evaluated the association between physical activity (including moderate to vigorous physical activity [MVPA], vigorous physical activity [VPA], and accelerometer assessed physical activity) and sedentary behaviors (including television watching, computer use, and driving) with the risk of sepsis. This assessment was based on whole-genome association study data from the UK Biobank and the FinnGen database. Causal inferences were estimated using inverse variance-weighted, weighted median, and MR-Egger methods. Sensitivity analyses were performed using Cochran's Q test, the MR-Egger intercept test, and the leave-one-out method. Results: The risk of sepsis was significantly inversely associated with genetically predicted MVPA (odds ratio [OR] 0.47, 95% confidence interval [CI] 0.24-0.93, P = 0.0296) and VPA alone (OR 0.19, 95% CI 0.04-0.87, P = 0.0324). Conversely, prolonged driving time showed a significant positive association with the risk of sepsis (OR 3.99, 95% CI 1.40-11.40, P = 0.0097). Conclusion: This study provides preliminary evidence of a causal relationship between MVPA and VPA and a reduced risk of sepsis, while prolonged sedentary behaviors such as driving are positively associated with an increased risk of sepsis. These findings provided essential scientific evidence for the development of effective sepsis prevention strategies.

Comparison of ocular biometric parameters between two swept-source optical coherence tomography devices and Scheimpflug tomography in patients with cataract.

AIM: To assess and compare the variations and agreements across different ocular biometric parameters using swept-source optical coherence tomography (SS-OCT) and Scheimpflug tomography in patients diagnosed with cataract. METHODS: This prospective case series was conducted at Tianjin Medical University Eye Hospital. In total, 212 eyes from 212 patients scheduled for phacoemulsification were included. Eyes were evaluated preoperatively using two SS-OCT devices (IOLMaster700 and CASIA2) and Scheimpflug tomography (Pentacam). Central corneal thickness (CCT), anterior chamber depth (ACD), aqueous depth (AQD), white-to-white distance (WTW), flat simulated keratometry (Kf), steep simulated keratometry (Ks), mean keratometry (Km), and total corneal keratometry (TKm) were measured. Intraclass correlation coefficient (ICC), 95% confidence intervals (CI) and limits of agreement (LoA) widths were conducted to assess differences and correlations between devices. RESULTS: All parameters, except for Ks, were significantly different. Pairwise comparison revealed no significant differences between keratometry obtained by IOLMaster 700 and Pentacam. LoA widths of all paired comparisons for Ks were >0.80 D. Except for WTW between IOLMaster 700 and CASIA2 and between CASIA2 and Pentacam, other Pearson's coefficients between devices showed a strong correlation (all r>0.95). The ICC of WTW (ICC=0.438, 95%CI 0.167-0.625) showed poor reliability. The reliability of CCT, ACD, and AQD was excellent (all ICC>0.95), whereas that of TKm was good (ICC=0.827, 95%CI 0.221-0.939). A significant linear correlation was also observed among devices. CONCLUSION: The ocular parameters derived from the use of IOLMaster700, CASIA2, and Pentacam exhibit significant discrepancies; as such, measurements from these devices should not be deemed as interchangeable.

Intrinsic oxidase-mimicking activity of nitrite upon visible light illumination and its colorimetric detection in saliva.

Small molecules with enzyme-like properties have recently attracted considerable attention. Herein, we discovered that nitrite possesses intrinsic oxidase-mimicking activity upon visible light, catalyzing the oxidation of the typical chromogenic substrate in the absence of H2O2. Notably, nitrite exhibited a markedly high value of Kcat, approximately 4, 7, and 4000-fold greater than that of Acr+-Mes, Eosin Y, and Diacetyl, respectively. Comprehensive investigation elucidated that O2•⁻ and •OH are the primary reactive oxygen species (ROS) responsible for the oxidation of 3,3',5,5'-tetramethylbenzidine dihydrochloride hydrate (TMB). Leveraging the linear correlation between the absorbance of oxidized TMB (oxTMB) at 652 nm and nitrite concentration, a simple colorimetric approach for nitrite detection was successfully established in the range of 1-75 µM with a detection limit of 0.14 µM. Moreover, the proposed strategy could be applied to determine the nitrite concentration in saliva, exhibiting a great prospect for clinical diagnosis. This work contributes novel insights into the exploration of small-molecule enzyme mimics.

Both hormones and energy-rich compounds play a role in the mitigation of elevated pH on aluminum toxicity in Citrus sinensis leaves.

The contribution of plant hormones and energy-rich compounds and their metabolites (ECMs) in alleviating aluminum (Al) toxicity by elevated pH remains to be clarified. For the first time, a targeted metabolome was applied to identify Al-pH-interaction-responsive hormones and ECMs in Citrus sinensis leaves. More Al-toxicity-responsive hormones and ECMs were identified at pH 4.0 [4 (10) upregulated and 7 (17) downregulated hormones (ECMs)] than those at pH 3.0 [1 (9) upregulated and 4 (14) downregulated hormones (ECMs)], suggesting that the elevated pH improved the adaptation of hormones and ECMs to Al toxicity in leaves. The roles of hormones and ECMs in reducing leaf Al toxicity mediated by elevated pH might include the following aspects: (a) improved leaf growth by upregulating the levels of jasmonoyl-L-isoleucine (JA-ILE), 6-benzyladenosine (BAPR), N6-isopentenyladenosine (IPR), cis-zeatin-O-glucoside riboside (cZROG), and auxins (AUXs), preventing Al toxicity-induced reduction of gibberellin (GA) biosynthesis, and avoiding jasmonic acid (JA)-mediated defense; (b) enhanced biosynthesis and accumulation of tryptophan (TRP), as well as the resulting increase in biosynthesis of auxin, melatonin and secondary metabolites (SMs); (c) improved ability to maintain the homeostasis of ATP and other phosphorus (P)-containing ECMs; and (d) enhanced internal detoxification of Al due to increased organic acid (OA) and SM accumulation and elevated ability to detoxify reactive oxygen species (ROS) due to enhanced SM accumulation. To conclude, the current results corroborate the hypotheses that elevated pH reduces Al toxicity by upregulating the ability to maintain the homeostasis of ATP and other P-containing ECMs in leaves under Al toxicity and (b) hormones participate in the elevated pH-mediated alleviation of Al toxicity by positively regulating growth, the ability to detoxify ROS, and the internal detoxification of Al in leaves under Al toxicity. Our findings provide novel insights into the roles of hormones and ECMs in mitigating Al toxicity mediated by the elevated pH.

Single-cell landscape of alternative polyadenylation in human lymphoid hematopoiesis.

Alternative polyadenylation (APA) is an essential post-transcriptional process that produces mature mRNA isoforms by regulating the usage of polyadenylation sites (PASs). APA is involved in lymphocyte activation; however, its role throughout the entire differentiation trajectory remains elusive. Here, we analyzed single-cell 3'-end transcriptome data from healthy subjects to construct a dynamic-APA landscape from hematopoietic stem and progenitor cells (HSPCs) to terminally differentiated lymphocytes. This analysis covered 19973 cells of 12 clusters from five lineages (B cells, CD4+ T cells, CD8+ T cells, natural killer cells, and plasmacytoid dendritic cells). A total of 2364 genes exhibited differential 3'UTR PAS usage, and 3021 genes displayed differential intronic cleavage during lymphoid differentiation. We observed a global trend of 3'UTR shortening during lymphoid differentiation. Nevertheless, specific events of both 3'UTR shortening and lengthening were also identified within each cluster. The APA patterns delineated three differentiation stages: HSPCs, precursor cells, and mature cells. Moreover, we demonstrated that the conversion of naïve T cells to memory T cells was accompanied by dynamic APA in transcription factor-encoding genes (TCF7 and NFATC2IP), immune function-related genes (BCL2, CD5, CD28, GOLT1B, and TMEM59), and protein ubiquitination-related genes (UBE2G1, YPEL5, and SUMO3). These findings expand our understanding of the underlying molecular mechanisms of APA and facilitate studies on the regulatory role of APA in lymphoid hematopoiesis.

Adaptive Responses of Hormones to Nitrogen Deficiency in Citrus sinensis Leaves and Roots.

Some citrus orchards in China often experience nitrogen (N) deficiency. For the first time, targeted metabolomics was used to examine N-deficient effects on hormones in sweet orange (Citrus sinensis (L.) Osbeck cv. Xuegan) leaves and roots. The purpose was to validate the hypothesis that hormones play a role in N deficiency tolerance by regulating root/shoot dry weight ratio (R/S), root system architecture (RSA), and leaf and root senescence. N deficiency-induced decreases in gibberellins and indole-3-acetic acid (IAA) levels and increases in cis(+)-12-oxophytodienoic acid (OPDA) levels, ethylene production, and salicylic acid (SA) biosynthesis might contribute to reduced growth and accelerated senescence in leaves. The increased ethylene formation in N-deficient leaves might be caused by increased 1-aminocyclopropanecarboxylic acid and OPDA and decreased abscisic acid (ABA). N deficiency increased R/S, altered RSA, and delayed root senescence by lowering cytokinins, jasmonic acid, OPDA, and ABA levels and ethylene and SA biosynthesis, increasing 5-deoxystrigol levels, and maintaining IAA and gibberellin homeostasis. The unchanged IAA concentration in N-deficient roots involved increased leaf-to-root IAA transport. The different responses of leaf and root hormones to N deficiency might be involved in the regulation of R/S, RSA, and leaf and root senescence, thus improving N use efficiency, N remobilization efficiency, and the ability to acquire N, and hence conferring N deficiency tolerance.

Basic study on cryopreservation of rat calvarial osteoblasts with different cryoprotectants.

Cryopreservation is a method adopted for storage of autologous skulls. Herein, this current research sought to explore the effects of different cryoprotectants on the biological characteristics of rat calvarial osteoblasts after cryopreservation. Neonatal Sprague-Dawley rats were selected and their skull tissues were isolated. The skull tissues were allocated into the refrigerating-3M, refrigerating-6M, M199-3M, M199-6M, povidone iodine-3M, and povidone iodine-6M groups according to the usage of cryoprotectants and treatment time (month) and the fresh group. Osteoblasts were isolated from skull tissues in each group through digestion. The histomorphology of the skull was evaluated by H&E staining and cell morphology was observed by microscopy. The viability, proliferation, apoptosis, and osteogenic activity of osteoblasts were assessed by trypan blue staining, MTT, flow cytometry, and alkaline phosphatase (ALP) staining. The skull histomorphology and osteoblast morphology were similar between the fresh and refrigerating groups. Osteoblast viability was weakened after cryopreservation. The longer the refrigeration time, the lower the number of living cells and the higher the apoptosis rate. However, cryopreservation using different cryoprotectants did not evidently affect osteoblast proliferation and ALP activity. Different cryoprotectants show no apparent effect on the osteogenic activity of rat calvarial osteoblasts after cryopreservation.

Comparative Study on the Mechanism of Macrophage Activation Induced by Polysaccharides from Fresh and Dried Longan.

Longan (Dimcarpus longan Lour.) is a kind of traditional fruit used as a medicine and a food. Fresh longan is primarily consumed as a fruit, whereas dried longan is commonly employed for medicinal purposes. The differences in the immunomodulatory activities and mechanisms of polysaccharides between dried and fresh longan remain unclear. The present study comparatively analyzed the mechanisms of macrophage activation induced by polysaccharides from dried (LPG) and fresh longan (LPX). The results revealed that LPG and LPX differentially promoted macrophage phagocytosis and the secretion of NO, TNF-α, and IL-6. RNA-seq analysis revealed that LPG and LPX differentially affected gene expression in macrophages. The LPG treatment identified Tnf and chemokine-related genes as core genes, while myd88 and interferon-related genes were the core genes affected by LPX. A comprehensive analysis of the differentially expressed genes showed that LPG initiated macrophage activation primarily through the TLR2/4-mediated TRAM/TRAF6 and CLR-mediated Src/Raf1 NF-κB signaling pathways. LPX initiated macrophage activation predominantly via the CLR-mediated Bcl10/MALT1 and NLR-mediated Rip2/TAK1 MAPK and NF-κB signaling pathways. Interestingly, the non-classical NF-κB signaling pathway was activated by polysaccharides in both dried and fresh longan to elicit a slow, mild immune response. LPG tends to promote immune cell migration to engage in the immune response, while LPX facilitates antigen presentation to promote T cell activation. These findings contribute insights into the mechanisms underlying the differences in bioactivity between dried and fresh longan and their potential applications in immune-enhancing strategies and functional-food development.

Association between preoperative anxiety states and postoperative complications in patients with esophageal cancer and COPD: a retrospective cohort study.

BACKGROUND: Esophageal cancer brings emotional changes, especially anxiety to patients. Co-existing anxiety makes the surgery difficult and may cause complications. This study aims to evaluate effects of anxiety in postoperative complications of esophageal cancer patients with chronic obstructive pulmonary disease (COPD). METHODS: Patients with esophageal cancer and co-existing COPD underwent tumor excision. Anxiety was measured using Hospital Anxiety and Depression Scale (HAD) before surgery. Clavien-Dindo criteria were used to grade surgical complications. A multiple regression model was used to analyze the relationship between anxiety and postoperative complications. The chi-square test was used to compare the differences in various types of complications between the anxiety group and the non-anxiety group. A multinomial logistic regression model was used to analyze the influencing factors of mild and severe complications. RESULTS: This study included a total of 270 eligible patients, of which 20.7% had anxiety symptoms and 56.6% experienced postoperative complications. After evaluation by univariate analysis and multivariate logistic regression models, the risk of developing complications in anxious patients was 4.1 times than non-anxious patients. Anxious patients were more likely to develop pneumonia, pyloric obstruction, and arrhythmia. The presence of anxiety, surgical method, higher body mass index (BMI), and lower preoperative oxygen pressure may increase the incidence of minor complications. The use of surgical methods, higher COPD assessment test (CAT) scores, and higher BMI may increase the incidence of major complications, while anxiety does not affect the occurrence of major complications (P = 0.054). CONCLUSION: Preoperative anxiety is associated with postoperative complications in esophageal cancer patients with co-existing COPD. Anxiety may increase the incidence of postoperative complications, especially minor complications in patient with COPD and esophageal cancer.

Solving the non-submodular network collapse problems via Decision Transformer.

Given a graph G, the network collapse problem (NCP) selects a vertex subset S of minimum cardinality from G such that the difference in the values of a given measure function f(G)-f(G∖S) is greater than a predefined collapse threshold. Many graph analytic applications can be formulated as NCPs with different measure functions, which often pose a significant challenge due to their NP-hard nature. As a result, traditional greedy algorithms, which select the vertex with the highest reward at each step, may not effectively find the optimal solution. In addition, existing learning-based algorithms do not have the ability to model the sequence of actions taken during the decision-making process, making it difficult to capture the combinatorial effect of selected vertices on the final solution. This limits the performance of learning-based approaches in non-submodular NCPs. To address these limitations, we propose a unified framework called DT-NC, which adapts the Decision Transformer to the Network Collapse problems. DT-NC takes into account the historical actions taken during the decision-making process and effectively captures the combinatorial effect of selected vertices. The ability of DT-NC to model the dependency among selected vertices allows it to address the difficulties caused by the non-submodular property of measure functions in some NCPs effectively. Through extensive experiments on various NCPs and graphs of different sizes, we demonstrate that DT-NC outperforms the state-of-the-art methods and exhibits excellent transferability and generalizability.

Survival benefits of adjuvant chemotherapy for patients with residual pathologic disease after neoadjuvant chemotherapy and surgery for locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Although preoperative neoadjuvant chemotherapy (NACT) or chemoradiation is the current standard of care for esophageal cancer in China, the impact of subsequent adjuvant therapy on patient prognosis remains unknown. This study aims to analyze the effect of adjuvant chemotherapy (ACT) on the survival rates of patients who have achieved a non-pathological complete response (non-pCR) after NACT and subsequent surgery. METHODS: We reviewed the data of 2193 patients with locally advanced thoracic esophageal squamous cell carcinoma (ESCC) who underwent radical surgery between January 2006 and January 2016. Of these patients, 46 received NACT and ACT, while 109 received NACT only. Propensity score matching was used to compare 86 patients, with 43 patients in the NACT + ACT group and 43 patients in the NACT group. Univariate analysis was performed using the Kaplan-Meier method and log-rank test, while Cox regression analysis was used for multivariate analysis. RESULTS: Multivariate analysis revealed that pathological lymph node status (positive vs negative) (P < .001) and treatment modalities (NACT + ACT vs NACT) (P = .005) were independent prognostic factors. There was a significant difference in long-term survival rates between the NACT + ACT and NACT groups, with 5-year survival rates of 55.8% vs 39.5%, respectively (χ2 = 4.270, P = .039). In patients with ypN+ status, the 5-year survival rate was 31.8% for those who received ACT after NACT and surgery, compared to 10.0% for those who did not receive additional ACT (χ2 = 6.101, P = .014). The corresponding percentages in patients with ypN- were 81.0% and 65.2%, respectively (χ2 = 1.993, P = .158). CONCLUSION: Adjuvant chemotherapy should be recommended for locally advanced ESCC patients with residual cancer after NACT and surgery, especially for patients with nodal metastases after NACT.

Reduced contrast sensitivity function is correlated with changes to cone photoreceptors in simple high myopia.

Purpose: To investigate the contrast sensitivity function (CSF) changes in simple high myopia (SHM) and evaluate the correlations between these changes with the early changes in the retinal microstructure. Methods: This prospective study comprised 81 subjects, 20 with emmetropia (EM), 26 with low myopia and moderate myopia (LM/MM), and 35 with SHM. The area under the log CSF curve (AULCSF) and the cut-off spatial frequency (Cut-off SF) were employed as measures of CSF. Adaptive optics (AO) was employed to quantify the cone density, spacing, and regularity. The thickness and blood flow of the retinal sublayers were determined from vertical and horizontal optical coherence tomography angiography (OCTA) A-scans. Swept-source optical coherence tomography (SS-OCT) was employed to analyze the choroidal thickness (CT) and choroidal vascularity using a custom algorithm. Differences in the retinal and choroidal parameters, cone distribution, AULCSF, and Cut-off SF were compared among the three groups. Multivariate linear mixed models were used to elucidate the associations between photoreceptor morphological alterations, retinal and choroidal parameters, and AULCSF. Results: The AULCSF and Cut-off SF were significantly lower in the SHM group compared to the EM and LM groups (p < 0.05). The SHM group had less cone density, larger cone spacing, and lower cone regularity than the EM and LM/MM groups (p < 0.05). Moreover, the thickness of the inner segment of photoreceptors (IS), retinal pigment epithelium (RPE) layer and choroid were reduced, and the outer segment of photoreceptors (OS) was thicker in the SHM group compared to the EM and LM/MM groups (all p < 0.05). A longer axial length (AL) was correlated with decreased AULCSF, cone density, and cone spacing (r = -0.800 to 0.752, all p < 0.050). Additionally, decreased CSF was correlated with lower cone density (r = 0.338, p = 0.035). Conclusion: Decreased contrast sensitivity was observed in patients with SHM and cone density was significantly correlated with reduced AUCSF.

Fraction Dose Escalation of Hypofractionated Radiotherapy with Concurrent Chemotherapy and Subsequent Consolidation Immunotherapy in Locally Advanced Non-Small Cell Lung Cancer: A Phase I Study.

PURPOSE: This phase I trial aimed to determine the maximum tolerated fraction dose (MTFD) of hypofractionated radiotherapy (hypo-RT) combined with concurrent chemotherapy and subsequent consolidation immune checkpoint inhibitors (cICI) for patients with locally advanced non-small cell lung cancer. PATIENTS AND METHODS: Split-course hypo-RT and hypoboost combined with concurrent chemotherapy was administered at three dose levels (DL), using a stepwise dose-escalation protocol. The sophisticated esophagus-sparing technique was implemented to restrict the dose to the esophagus. Patients who did not experience disease progression or unresolved ≥grade 2 (G2+) toxicities after RT received cICI. Each DL aimed to treat six patients. The MTFD was defined as the highest DL at which ≤2 patients of the six who were treated experienced treatment-related G3+ toxicity and ≤1 patient experienced G4+ toxicity within 12 months post-RT. RESULTS: Eighteen patients were enrolled, with six patients in each DL. All patients completed hypo-RT and concurrent chemotherapy, and 16 (88.9%) received at least one infusion of cICI, with a median of 10 infusions. Within the 12-month assessment period, one patient in DL1 experienced G3 pneumonitis, and one patient in DL3 developed G3 tracheobronchitis. The MTFD was not reached. The objective response rate was 100%. With a median follow-up of 20.9 months, the 1-year overall survival and progression-free survival rates were 94.4% and 83.3%, respectively. CONCLUSIONS: Utilizing the split-course hypo-RT and hypoboost approach, a fraction dose of 5 Gy to a total dose of 60 Gy, combined with concurrent chemotherapy and subsequent cICI, was well tolerated and yielded a promising objective response rate and survival outcomes.

Toward Robust Self-Training Paradigm for Molecular Prediction Tasks.

Molecular prediction tasks normally demand a series of professional experiments to label the target molecule, which suffers from the limited labeled data problem. One of the semisupervised learning paradigms, known as self-training, utilizes both labeled and unlabeled data. Specifically, a teacher model is trained using labeled data and produces pseudo labels for unlabeled data. These labeled and pseudo-labeled data are then jointly used to train a student model. However, the pseudo labels generated from the teacher model are generally not sufficiently accurate. Thus, we propose a robust self-training strategy by exploring robust loss function to handle such noisy labels in two paradigms, that is, generic and adaptive. We have conducted experiments on three molecular biology prediction tasks with four backbone models to gradually evaluate the performance of the proposed robust self-training strategy. The results demonstrate that the proposed method enhances prediction performance across all tasks, notably within molecular regression tasks, where there has been an average enhancement of 41.5%. Furthermore, the visualization analysis confirms the superiority of our method. Our proposed robust self-training is a simple yet effective strategy that efficiently improves molecular biology prediction performance. It tackles the labeled data insufficient issue in molecular biology by taking advantage of both labeled and unlabeled data. Moreover, it can be easily embedded with any prediction task, which serves as a universal approach for the bioinformatics community.

Metabolomic profiling of serum and tongue coating of pregnant women with intrahepatic cholestasis in pregnancy.

Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of cesarean section and adverse fetal outcomes. Currently, ICP diagnosis depends largely on serum levels of bile acids and lacks sensitivity and specificity for accurate diagnosis. Tongue diagnosis is an important diagnostic tool in traditional Chinese medicine (TCM) and is used in our clinic as complementary treatment and personalized medicine for ICP. However, the molecular basis of the manifestation of greasy white tongue coatings in ICP remains unknown. In this study, we performed untargeted metabolomic profiling of the serum, tongue coating, and saliva of 66 pregnant women, including 22 with ICP. The metabolomic profiles of the serum and tongue coatings showed marked differences between the two clinical groups. Forty-six differentially abundant metabolites were identified, and their relative concentrations correlated with total bile acid levels. These differential metabolites included bile acids, lipids, microbiota- and diet-related metabolites, and exposomes. Conventional biochemical markers, including serum aminotransferases and bilirubin, were not significantly increased in the ICP group, whereas the total cholesterol and triglyceride levels were significantly increased as early as the first trimester. Our data provide insights into the pathophysiology of ICP and implicate the gut-liver axis and environmental exposure. Tongue coating has the potential to be a non-invasive diagnostic approach. Further studies are required to validate the clinical utility of these findings.

Appropriate addition power for aphakic infants determined by a smart wearable device Clouclip.

CLINICAL RELEVANCE: It is particularly important to perform reasonable and effective optical correction to enable visual development after primary lens removal surgery for congenital cataracts. Aphakic infants need a suitable addition power of prescription (ADD) to help them focus on close visual objects. BACKGROUND: It is challenging to obtain appropriate ADD power for infants due to poor cooperation and lack of subjective feedback. We aimed to determine the appropriate ADD for aphakic infants using a recently developed smart wearable device called Clouclip. METHODS: The study was a cross-sectional, observational pilot study. Twenty-three aphakic infants (aged from 6 months to 3.5 years) were invited to wear a smart wearable device for 7 days consecutively to monitor the near viewing distance in real life. Viewing habits and its associations with the possible influencing factors were investigated based on the data obtained from the device. RESULTS: The average proportion of near viewing time was 77.9% (95% confidence interval (CI) 72.1-83.7%). The average of the median near viewing distance was 23.8 cm (95% CI 20.6 cm-27.0 cm), which corresponded to an ADD of +4.25 D (95% CI + 3.75 D - +4.75 D) spectacle prescription. The height of the child was found to be positively correlated with the median of near viewing distance (r = 0.646, p = 0.001). Age, current ADD, age of cataract extraction surgery and bilaterality or monocularity of the aphakic eyes showed no significant correlation with the aforementioned viewing habits (all p > 0.05). CONCLUSION: By using the novel wearable device, we found the suitable ADD of spectacle prescription for aphakic infants is about +4.25 D. The height of the child was an influencing factor for ADD.