Clinical efficacy of laparoscopic cholecystectomy plus cholangioscopy for the treatment of cholecystolithiasis combined with choledocholithiasis.

BACKGROUND: Currently, endoscopic retrograde cholangiopancreatography (ERCP) plus laparoscopic cholecystectomy (LC) is the main treatment for cholecystolithiasis combined with choledocholithiasis. However, the treatment is unsatisfactory, and the development of better therapies is needed. AIM: To determine the clinical efficacy of LC plus cholangioscopy for cholecystolithiasis combined with choledocholithiasis. METHODS: Patients (n = 243) with cholecystolithiasis and choledocholithiasis admitted to The Affiliated Haixia Hospital of Huaqiao University (910th Hospital of Joint Logistic Support Force) between January 2019 and December 2023 were included in the study; 111 patients (control group) underwent ERCP + LC and 132 patients (observation group) underwent LC + laparoscopic common bile duct exploration (LCBDE). Surgical success rates, residual stone rates, complications (pancreatitis, hyperamylasemia, biliary tract infection, and bile leakage), surgical indicators [intraoperative blood loss (IBL) and operation time (OT)], recovery indices (postoperative exhaust/defecation time and hospital stay), and serum inflammatory markers [C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were compared. RESULTS: No significant differences in surgical success rates and residual stone rates were detected between the observation and control groups. However, the complication rate, IBL, OT, postoperative exhaust/defecation time, and hospital stays were significantly reduced in the observation group compared with the control group. Furthermore, CRP, TNF-α, and IL-6 Levels after treatment were reduced in the observation group compared with the levels in the control group. CONCLUSION: These results indicate that LC + LCBDE is safer than ERCP + LC for the treatment of cholecystolithiasis combined with choledocholithiasis. The surgical risks and postoperative complications were lower in the observation group compared with the control group. Thus, patients may recover quickly with less inflammation after LCBDE.

Diagnostic significance of serum levels of serum amyloid A, procalcitonin, and high-mobility group box 1 in identifying necrotising enterocolitis in newborns.

BACKGROUND: Necrotising enterocolitis (NEC) is a critical gastrointestinal emergency affecting premature and low-birth-weight neonates. Serum amyloid A (SAA), procalcitonin (PCT), and high-mobility group box 1 (HMGB1) have emerged as potential biomarkers for NEC due to their roles in inflammatory response, tissue damage, and immune regulation. AIM: To evaluate the diagnostic value of SAA, PCT, and HMGB1 in the context of NEC in newborns. METHODS: The study retrospectively analysed the clinical data of 48 newborns diagnosed with NEC and 50 healthy newborns admitted to the hospital. Clinical, radiological, and laboratory findings, including serum SAA, PCT, and HMGB1 Levels, were collected, and specific detection methods were used. The diagnostic value of the biomarkers was evaluated through statistical analysis, which was performed using chi-square test, t-test, correlation analysis, and receiver operating characteristic (ROC) analysis. RESULTS: The study demonstrated significantly elevated levels of serum SAA, PCT, and HMGB1 Levels in newborns diagnosed with NEC compared with healthy controls. The correlation analysis indicated strong positive correlations among serum SAA, PCT, and HMGB1 Levels and the presence of NEC. ROC analysis revealed promising sensitivity and specificity for serum SAA, PCT, and HMGB1 Levels as potential diagnostic markers. The combined model of the three biomarkers demonstrating an extremely high area under the curve (0.908). CONCLUSION: The diagnostic value of serum SAA, PCT, and HMGB1 Levels in NEC was highlighted. These biomarkers potentially improve the early detection, risk stratification, and clinical management of critical conditions. The findings suggest that these biomarkers may aid in timely intervention and the enhancement of outcomes for neonates affected by NEC.

Advanced electrochemical membrane technologies for near-complete resource recovery and zero-discharge of urine: Performance optimization and evaluation.

The depletion of nutrient sources in fertilizers demands a paradigm shift in the treatment of nutrient-rich wastewater, such as urine, to enable efficient resource recovery and high-value conversion. This study presented an integrated bipolar membrane electrodialysis (BMED) and hollow fiber membrane (HFM) system for near-complete resource recovery and zero-discharge from urine treatment. Computational simulations and experimental validations demonstrated that a higher voltage (20 V) significantly enhanced energy utilization, while an optimal flow rate of 0.4 L/min effectively mitigated the negative effects of concentration polarization and electro-osmosis on system performance. Within 40 min, the process separated 90.13% of the salts in urine, with an energy consumption of only 8.45 kWh/kgbase. Utilizing a multi-chamber structure for selective separation, the system achieved recovery efficiencies of 89% for nitrogen, 96% for phosphorus, and 95% for potassium from fresh urine, converting them into high-value products such as 85 mM acid, 69.5 mM base, and liquid fertilizer. According to techno-economic analysis, the cost of treating urine using this system at the lab-scale was $6.29/kg of products (including acid, base, and (NH4)2SO4), which was significantly lower than the $20.44/kg cost for the precipitation method to produce struvite. Excluding fixed costs, a net profit of $18.24/m3 was achieved through the recovery of valuable products from urine using this system. The pilot-scale assessment showed that the net benefit amounts to $19.90/m3 of urine, demonstrating significant economic feasibility. This study presents an effective approach for the near-complete resource recovery and zero-discharge treatment of urine, offering a practical solution for sustainable nutrient recycling and wastewater management.

A short-term functional recovery comparison of therapeutic plasma exchange and immunoadsorption in severe acute neuroimmune diseases.

OBJECTIVE: To compare the differential impact of recombinant protein A immunoadsorption (PAIA) or therapeutic plasma exchange (TPE) on neurological functional improvement and quality of life in patients afflicted with severe acute neuroimmune diseases, including Guillain-Barré syndrome (GBS), myasthenia gravis (MG), neuromyelitis optica spectrum disorder (NMOSD), and anti-NMDA receptor encephalitis (NMDARE). METHODS: The retrospective study included 29 patients with moderate to severe disability (modified Rankin scale, mRS≥3) due to acute neuroimmune diseases at the second Xiangya hospital from January 2021 to January 2023. The clinical efficacy of PAIA and TPE in improving neurological function (ΔmRS≥1) and the difference in favorable functional outcomes (mRS 0-2) at three months were evaluated. The impact of both treatments on patients' health-related quality of life (HRQoL) was assessed using a visual analog scale (EQ-VAS) score ranging from 0 to 100. RESULTS: The findings revealed that the PAIA group exhibited a significantly higher rate of improvement in modified Rankin scale (mRS) scores (ΔmRS≥1) at the three-month follow-up compared to the TPE group (94.4 % vs. 54.5 %, p = 0.018). However, no statistically significant difference was observed between the two treatment modalities in terms of favorable neurological functional outcomes at the three-month mark. Furthermore, the PAIA group demonstrated a significantly higher EQ-VAS score at 14 days post-treatment compared to the TPE group (60.0 vs. 47.7, p = 0.017). CONCLUSION: In the short-term management of severe acute neuroimmune diseases, PAIA may present a greater probability of improving neurological function and facilitating an earlier enhancement of quality of life compared to TPE.

The Formation Mechanism of Carbonized Polymer Dots: Crosslinking-Induced Nucleation and Carbonization.

Carbon dots (CDs), as a kind of zero-dimensional nanomaterials, have been widely synthesized by bottom-up methods from various precursors. However, the formation mechanism is still unclear and controversial, which also brings difficulty to the regulation of structures and properties. Only some tentative formation processes were postulated by analyzing the products obtained at different reaction times and temperatures. Here, the effect of crosslinking on the formation of carbonized polymer dots (CPDs) is explored. Crosslinking-induced nucleation and carbonization (CINC) is proposed as the driving force for the formation of CPDs. Under hydrothermal synthesis, the precursors are initiated to polymerize and crosslink. The crosslinking brings higher hydrophobicity to generate the hydrophilic/hydrophobic microphase separation, which promotes dehydration and carbonization resulting in the formation of CPDs. Based on the principle of CINC, the influence factors of size are also revealed. Moreover, the dissipative particle dynamics (DPD) simulation is employed to support this formation mechanism. This concept of CINC will bring light to the formation process of CPDs, as well as facilitate the regulation of CPDs' size and photoluminescence.

Inflammatory Trajectory and Anti-Inflammatory Pharmacotherapy in Frozen Elephant Trunk-Treated Acute Type I Aortic Dissection.

Background: Acute DeBakey type I aortic dissection is associated with high morbidity and mortality. Little is known regarding the role of leukocyte trajectory in prognosis. Methods: We included adult acute DeBakey type I aortic dissection patients with emergency frozen elephant trunk and total arch replacement in 2 cardiovascular centers (2020-2022). We used latent class mixed model to group patients according to their leukocyte patterns from hospital admission to the first 5 days after surgery. We investigated the association of leukocyte trajectory and 30-day and latest follow-up mortality (October 31, 2023), exploratorily analyzing the effects of ulinastatin treatment on outcome. Results: Of 255 patients included, 3 distinct leukocyte trajectories were identified: 196 in group I (decreasing trajectory), 34 in group II (stable trajectory), and 25 in group III (rising trajectory). Overall, 30-day mortality was 25 (9.8%), ranging from 8.2% (16/196) in group I, 8.8% (3/34) in group II, to 24.0% (6/25) in group III (P for trend = .036). Group III was associated with higher mortality both at 30 days (adjusted hazard ratio, 3.260; 95% CI, 1.071-9.919; P = .037) and at the last follow-up (adjusted hazard ratio, 2.840; 95% CI, 1.098-7.345; P = .031) compared with group I. Conclusions: Distinct and clinically relevant groups can be identified by analyzing leukocyte trajectories, and a rising trajectory was associated with higher short-term and midterm mortality.

Differential expression of microRNAs in giant freshwater prawn (Macrobrachium rosenbergii) during the infection of Vibrio parahaemolyticus.

MicroRNAs (miRNAs) are a category of small non-coding RNAs regarded as vital regulatory factors in various biological processes, especially immune regulation. The differently expressed miRNAs in Macrobrachium rosenbergii after the challenge of Vibrio parahaemolyticus were identified using high-throughput sequencing. A total of 18 known as well as 12 novel miRNAs were markedly differently expressed during the bacterial infection. The results of the target gene prediction and enrichment analysis indicated that a total of 230 target genes involved in a large variety of signaling pathways and biological processes were mediated by the miRNAs identified in the current research. Additionally, the effects of novel-miR-56, a representative differentially expressed miRNA identified in the previous infection experiment, on the immune-related gene expression in M. rosenbergii were explored. The expression of the immune-related genes including Spätzle1(Spz1), Spz4, Toll-like receptor 1 (TLR1), TLR2, TLR3, immune deficiency (IMD), myeloid differentiation factor 88 (MyD88), anti-lipopolysaccharide factor 1 (ALF1), crustin1, as well as prophenoloxidase (proPO) was significantly repressed in the novel-miR-56-overexpressed prawns. The expression of these genes tested in the novel-miR-56-overexpressed M. rosenbergii was still signally lower than the control in the subsequent V. parahaemolyticus challenge, despite the gene expression in each treatment increased significantly after the infection. Additionally, the cumulative mortality of the agomiR-56-treated prawns was significantly higher than the other treatments post the bacterial challenge. These results suggested that novel-miR-56 might function as a negative regulator of the immune-related gene expression of M. rosenbergii in the innate immune defense against V. parahaemolyticus.

Prevalence and genotype distribution of human papillomavirus infection among 66000 women from 2014 to 2023 in the plateau region of Southwest China.

BACKGROUND: Persistent infection with high-risk human papillomavirus (HR-HPV) plays a key role in the onset of cervical cancer. This study was designed to examine the epidemiological trends and genotype distribution of HPV from 2014 to 2023 in the plateau region of Southwest China. METHODS: The findings could offer valuable insights for clinical screening of cervical cancer and the formulation of HPV vaccination policies. This retrospective study analyzed 66,000 women who received HPV-DNA testing at the First People's Hospital of Qujing, Yunnan, China, between 2014 and 2023. The cohort consisted of 33,512 outpatients, 3,816 inpatients, and 28,672 individuals undergoing health examinations. Cervical cells were collected for DNA extraction, and PCR amplification along with Luminex xMAP technology were used to detect 27 HPV genotypes. The data analysis was conducted using GraphPad Prism and IBM SPSS Statistics 27 software. RESULTS: The overall HPV infection rate at the First People's Hospital of Qujing declined from 24.92% in 2014 to 16.29% in 2023, averaging 16.02%. Specific infection rates were 18.50% among outpatients, 12.97% among inpatients, and 13.53% for health examination attendees. The predominant high-risk HPV genotypes identified were HPV52 (2.61%), HPV16 (2.06%), HPV58 (1.81%), HPV53 (1.55%), and HPV39 (1.09%). Meanwhile, the most frequent low-risk HPV genotypes were HPV6 (1.30%), HPV61 (1.21%), and HPV11 (0.85%). In HPV-positive cases, the distribution of single, double, triple, and quadruple or more infections were 79.90%, 15.17%, 3.59%, and 1.33%, respectively. The proportions of pure LR-HPV, pure HR-HPV, and mixed infections were 22.16%, 67.82%, and 10.02%, respectively. Age-specific analysis revealed a bimodal distribution of HPV infection, with the infection rate rapidly decreasing from 44.02% in the ≤ 19 age group to 19.55% in the 20-29 age group and 13.84% in the 30-39 age group, followed by a gradual increase to 14.64% in the 40-49 age group, 16.65% in the 50-59 age group, and 22.98% in the ≥ 60 age group. The coverage rates of the three available vaccines are all below 50%. The results of this study indicated a declining trend in HPV prevalence in the plateau region of Southwest China over the period from 2014 to 2023, especially in the reduction of genotypes targeted by vaccines. CONCLUSION: There were significant variations in the genotypes prevalent among different age groups, years, and patient sources within the same region. The underwhelming vaccination rates emphasize the critical need for developing either a multivalent vaccine or a personalized vaccine that targets the HPV genotypes common in the Chinese population. Furthermore, vaccinating adolescents to curb HPV infection and ensuring regular cervical cancer screenings for postmenopausal women are crucial steps.

Association between metabolic score for insulin resistance and regression to normoglycemia from prediabetes in Chinese adults: A retrospective cohort study.

BACKGROUND: Metabolic score for insulin resistance (METS-IR) is a surrogate index to estimate insulin sensitivity. The aim of this study was to examine the association between METS-IR and regression to normoglycemia in Chinese adults with prediabetes. METHODS: A total of 15,415 Chinese adults with prediabetes defined by their fasting blood glucose were included in this retrospective study. The association between METS-IR and regression to normoglycemia from prediabetes was evaluated using the Cox proportional hazards regression model. A Cox proportional hazards regression with cubic spline function was performed to explore the nonlinear association between METS-IR and regression to normoglycemia. Kaplan-Meier curves was used to describe the probability of regression to normoglycemia from prediabetes. RESULTS: In multivariate Cox proportional hazards regression analyses, the increase in METS-IR was independently associated with a reduced probability of regression to normoglycemia from prediabetes (all p < 0.01 in models 1-3). A nonlinear association between METS-IR and the probability of regression to normoglycemia was observed, with an inflection point of 49.3. The hazard ratio on the left side of the inflection point was 0.965 (95% CI 0.953-0.976). Subgroup analyses demonstrated the robustness of our findings. CONCLUSION: This study demonstrated a negative and nonlinear association between METS-IR and regression to normoglycemia in Chinese adults with prediabetes. When METS-IR is below 49.3, reducing METS-IR could significantly increase the probability of regression to normoglycemia from prediabetes.

Performance Limits and Advancements in Single 2D Transition Metal Dichalcogenide Transistor.

Two-dimensional (2D) transition metal dichalcogenides (TMDs) allow for atomic-scale manipulation, challenging the conventional limitations of semiconductor materials. This capability may overcome the short-channel effect, sparking significant advancements in electronic devices that utilize 2D TMDs. Exploring the dimension and performance limits of transistors based on 2D TMDs has gained substantial importance. This review provides a comprehensive investigation into these limits of the single 2D-TMD transistor. It delves into the impacts of miniaturization, including the reduction of channel length, gate length, source/drain contact length, and dielectric thickness on transistor operation and performance. In addition, this review provides a detailed analysis of performance parameters such as source/drain contact resistance, subthreshold swing, hysteresis loop, carrier mobility, on/off ratio, and the development of p-type and single logic transistors. This review details the two logical expressions of the single 2D-TMD logic transistor, including current and voltage. It also emphasizes the role of 2D TMD-based transistors as memory devices, focusing on enhancing memory operation speed, endurance, data retention, and extinction ratio, as well as reducing energy consumption in memory devices functioning as artificial synapses. This review demonstrates the two calculating methods for dynamic energy consumption of 2D synaptic devices. This review not only summarizes the current state of the art in this field but also highlights potential future research directions and applications. It underscores the anticipated challenges, opportunities, and potential solutions in navigating the dimension and performance boundaries of 2D transistors.

Association between serum uric acid to serum creatinine ratio with cardiovascular and all-cause mortality in adults with hypertension.

The serum uric acid to serum creatinine ratio (SUA/sCr) is a standardized index of renal function. More importance was attached to the significance of this ratio in the progression of hypertension. While the association between the prognosis of hypertension and SUA/sCr is unknown. Therefore, we aimed to prospectively examine the associations of serum uric acid to serum creatinine ratio and all-cause and CVD mortality in adults with hypertension. Participants with hypertension from NHANES 1999-2018 (n = 15,269) were included. They were stratified by 1 increment of SUA/sCr ratio and categorized into 6 groups as ≤ 4, > 4 to 5, > 5 to 6, > 6 to 7, > 7 to 8, and > 8. The reason for categorization in 6 groups was to analyze the influence of different ratios on outcomes accurately and provide more precise guidance. The sample size is large enough that even if divided into 6 groups, it does not affect the statistical power. The primary outcomes were all-cause and CVD mortality. Weighted multivariable Cox proportional hazards regression models were used to estimate hazard ratio (HRs) of mortality. Restricted cubic spline regression models were utilized to examine dose-response associations between the serum uric acid to serum creatinine ratio and all-cause and CVD mortality. Relatively comprehensive stratified analyses were conducted to confirm the accuracy and stability of the results. There were 15,269 total participants, 49.4% of whom were men, with an average age of 56.6 years. Weighted multivariable Cox proportional hazards regression models demonstrated participants in the lowest group (≤ 4) had the HRs (95% CIs) of 1.43 (1.18, 1.73) for all-cause mortality and 2.8 (1.92, 4.10) for CVD mortality when compared to the reference group. Participants in the highest group (> 8) had the HRs (95% CIs) of 0.47 (0.25, 0.89) for CVD mortality when compared to the reference group. There were progressively lower risks for all-cause and CVD mortality with the SUA/sCr ratio increased (both P trend < 0.01). The SUA/sCr ratio was (P for nonlinearity < 0.01) nonlinearly correlated with all-cause mortality, with inflection points of 6.25. In addition, the restricted cubic splines results indicated that the SUA/sCr ratio (P for nonlinearity = 0.32) showed linear and negative associations with cardiovascular mortality with inflection points of 6.54. The inverse associations between SUA/sCr ratio and all-cause mortality were consistent across all subgroups except for the subgroup of eGFR < 45 ml/min/1.73 m2 and never smokers (P trend = 0.20 and 0.13, respectively), and the inverse associations between low SUA/sCr ratio and CVD mortality were consistent across all subgroups (P trend < 0.01). Contrary to previous studies, outcomes suggest that lower SUA/sCr ratio was associated with higher risks of all-cause and CVD mortality in adults with hypertension.

Discovery of Curcuminoids as Pancreatic Lipase Inhibitors from Medicine-and-Food Homology Plants.

Researchers are increasingly interested in discovering new pancreatic lipase inhibitors as anti-obesity ingredients. Medicine-and-food homology plants contain a diverse set of natural bioactive compounds with promising development potential. This study screened and identified potent pancreatic lipase inhibitors from 20 commonly consumed medicine-and-food homology plants using affinity ultrafiltration combined with spectroscopy and docking simulations. The results showed that turmeric exhibited the highest pancreatic lipase-inhibitory activity, and curcumin, demethoxycurcumin, and bisdemethoxycurcumin were discovered to be potent pancreatic lipase inhibitors within the turmeric extract, with IC50 values of 0.52 ± 0.04, 1.12 ± 0.05, and 3.30 ± 0.08 mg/mL, respectively. In addition, the enzymatic kinetics analyses demonstrated that the inhibition type of the three curcuminoids was the reversible competitive model, and curcumin exhibited a higher binding affinity and greater impact on the secondary structure of pancreatic lipase than found with demethoxycurcumin or bisdemethoxycurcumin, as observed through fluorescence spectroscopy and circular dichroism. Furthermore, docking simulations supported the above experimental findings, and revealed that the three curcuminoids might interact with amino acid residues in the binding pocket of pancreatic lipase through non-covalent actions, such as hydrogen bonding and π-π stacking, thereby inhibiting the pancreatic lipase. Collectively, these findings suggest that the bioactive compounds of turmeric, in particular curcumin, can be promising dietary pancreatic lipase inhibitors for the prevention and management of obesity.

Precise detection of cell-type-specific domains in spatial transcriptomics.

Cell-type-specific domains are the anatomical domains in spatially resolved transcriptome (SRT) tissues where particular cell types are enriched coincidentally. It is challenging to use existing computational methods to detect specific domains with low-proportion cell types, which are partly overlapped with or even inside other cell-type-specific domains. Here, we propose De-spot, which synthesizes segmentation and deconvolution as an ensemble to generate cell-type patterns, detect low-proportion cell-type-specific domains, and display these domains intuitively. Experimental evaluation showed that De-spot enabled us to discover the co-localizations between cancer-associated fibroblasts and immune-related cells that indicate potential tumor microenvironment (TME) domains in given slices, which were obscured by previous computational methods. We further elucidated the identified domains and found that Srgn may be a critical TME marker in SRT slices. By deciphering T cell-specific domains in breast cancer tissues, De-spot also revealed that the proportions of exhausted T cells were significantly increased in invasive vs. ductal carcinoma.

Prospective, multicenter, self-controlled clinical trial on the effectiveness and safety of cable-transmission magnetically controlled capsule endoscope system for the examination of upper gastrointestinal diseases.

BACKGROUND AND AIMS: Many gastrointestinal (GI) disorders and precancerous conditions often present asymptomatically, leading to delayed patient diagnoses and treatment interventions. This study aimed to develop a novel cable-transmission magnetically controlled capsule endoscopy (CT-MCCE) system for detecting GI diseases and assess its safety and feasibility through clinical trials. METHODS: This prospective, multicenter, trial compared CT-MCCE with conventional gastroscopy in patients aged 18-75 years with upper GI diseases between October 2022 and May 2023. The primary endpoints included the evaluation of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in the detection of focal lesions within the esophagus, stomach, and duodenal bulb using CT-MCCE. RESULTS: A total of 180 individuals (mean age: 43.1 years, 52.22% female) were recruited from three hospitals in China. CT-MCCE detected lesions in esophagus with 97.22% sensitivity, 100% specificity, a PPV of 100%, a NPV of 98.18%, and 98.89% accuracy. CT-MCCE detected gastric focal lesions in the whole stomach with 96.81% sensitivity, 98.84% specificity, a PPV of 98.91%, a NPV of 96.59%, and 97.78% accuracy. CT-MCCE detected lesions in the duodenal bulb with 100% sensitivity, 100% specificity, a PPV of 100%, a NPV of 100%, and 100% accuracy. There were no significant differences between CT-MCCE and EGD regarding the cleanliness of the upper GI tract and visibility of the upper GI mucosa. However, CT-MCCE was associated with a lower incidence of discomfort than EGD (P<0.001). CONCLUSIONS: The diagnostic performance of CT-MCCE is comparable to that of EGD in the completion of upper GI tract examinations and lesion detection. Furthermore, the improved tolerance of CT-MCCE in detecting upper GI diseases was noted without any observed adverse events.

Event-related potentials of familiar monosyllabic words with unexpected lexical tones: A picture-word study of Mandarin-speaking preschoolers with and without a history of late talking.

This study examined how Mandarin-speaking preschoolers with and without a history of late talking (LT) process familiar monosyllabic words with unexpected lexical tones, focusing on both phonological and semantic violations. This study initially enrolled 64 Mandarin-speaking toddlers: 31 with a history of LT (mean age: 27.67 months) and 33 without a history of LT (non-LT) (mean age: 27.85 months). Event-related potentials were recorded at the age of 4 years during a picture-word mismatch task (LT mean age: 51.36 months; non-LT mean age: 51.20 months); in this task, the participants were presented with auditory words either matching (Tone 3) or mismatching with images in terms of their lexical tones; the mismatches encompassed acoustically dissimilar (Tone 1) and similar (Tone 2) mismatches. A significant difference in the phonological mapping negativity (PMN) responses to Tones 1 and 3 was observed only in the non-LT group. However, differences in the N400 responses to Tones 1 and 3 remained consistent across both groups. In addition, greater differences in the PMN responses between Tones 1 and 3 were associated with higher language proficiency during the preschool period. The PMN response serves as an indicator of neural correlates in lexical tone processing, reflecting challenges encountered by preschoolers with a history of LT when processing the lexical tones of familiar words. Furthermore, the PMN response was correlated with concurrent language abilities. These findings indicate the importance of early tonal perception development for Mandarin speakers with a history of LT. RESEARCH HIGHLIGHTS: Preschoolers with a history of late talking (LT), similar to preschoolers without such a history, can establish word expectations and detect the lexical tone violation in real time. However, those with a history of LT require additional time to process acoustic cues and differentiate between word semantics based on lexical tone information. The phonological mapping negativity response serves as an indicator of neural correlates in lexical tone processing, reflecting challenges encountered by preschoolers with a history of LT when processing the lexical tones of familiar words. The present findings indicate the importance of early intervention for Mandarin speakers with a history of LT, with an emphasis on lexical tone processing from toddlerhood.

Corrigendum: LC-MS/MS untargeted lipidomics uncovers placenta lipid signatures from intrahepatic cholestasis of pregnancy.

[This corrects the article DOI: 10.3389/fphys.2024.1276722.].

Etiologies of Persistent Aminotransferase Elevations in Chronic Hepatitis B Patients Treated with Nucleos(t)ide Analogs.

Background/Aims: Recent studies revealed that patients with persistent aminotransferase elevations after antiviral treatment had higher risk of hepatic events; yet its underlying causes remain unclear. Our study aimed to investigate the etiologies of persistent aminotransferase elevations in patients treated with nucleos(t)ide analogs (NAs). Materials and Methods: A retrospective study was conducted on chronic hepatitis B (CHB) patients who had been receiving NA treatment for over a year and had an aminotransferase level greater than 40 IU/mL (more than twice, with a 3-month interval) and subsequently underwent a liver biopsy. Results: The study group included 46 patients (34 males) with a mean age of 44.8 ± 20.3 years (range: 24-71 years).The average dura- tion of NA therapy was 3.7 years (1.1-10.6 years). The etiologies of persistant transaminase elevation were categorized into 4 groups: patients with low hepatitis B virus (HBV) viral load (LVL, n = 11); concurrent non-alcoholic fatty liver disease (NAFLD, n = 12); concurrent other liver diseases (OLD, n = 12); and unknown liver dysfunction (ULD, n = 11). The proportion of G ≥ 2 inflammation was significantly higher in the LVL group (90.9%) compared to NAFLD (33.3%), OLD (50%), and ULD (27.2%) groups (P = .012). The hepatitis B e-antigen (HBeAg)-positive group exhibited a younger age (34.5 ± 10.2 vs. 48.1 ± 9.4 years, P < .001), a lower proportion of fibrosis F ≥ 2 (36.3% vs. 77.1%, P = .012), and a higher prevalence of detectable HBV DNA (54.5% vs.14.2%, P = .00632) compared to the HBeAg-negative group. Conclusion: The etiology of persistent aminotransferase elevations in CHB patients undergoing NAs treatment warrants investigation. Besides the commonly observed NAFLD and low HBV viral load, concurrent presence of other liver diseases requires elucidation.The proportion of G≥2 inflammation was higher in the LVL group.

Development of a 2A peptide-based multigene expression system and its application for enhanced production of ganoderic acids in Ganoderma lucidum.

Ganoderma has received much attention for its medicinal value, but the manipulation of multiple genes remains a challenge, hindering the genetic engineering of this species for the development of cell factories. Here, we first showed that the presence of an intron is necessary for the efficient expression of the endogenous cDNA of carboxin-resistant gene (cbx) in G. lucidum. Then, the self-cleaving function of 2 A peptide was investigated in G. lucidum by linking cbx cDNA to the codon-optimized hygromycin B-resistant gene (ophph) using the 2A-peptide sequence. The results showed that cbx cDNA and ophph can be successfully expressed in G. lucidum in a bicistronic manner from a single transcript. Moreover, the expression of both genes was not affected by the order within the 2 A cassette. In addition, simultaneous expression of cbx cDNA, ophph, and codon-optimized yellow fluorescent protein gene (opyfp) was conducted for the first time in G. lucidum using the 2 A peptide-based approach. The developed method was successfully applied to express both cDNA of the 3-hydroxy-3-methylglutaryl coenzyme A reductase (hmgr) and squalene epoxidase gene (se) for enhanced production of ganoderic acids (GAs) in G. lucidum. The engineered strain produced the maximum content of GA-Mk, GA-T, GA-S, and GA-Me were 26.56±3.53,39.58±3.75, 16.54±2.16, and 19.1±1.87 µg/100 mg dry weight, respectively. These values were 3.85-, 4.74-, 3.65-, and 3.23-fold higher than those produced by the control strain. The developed method will be useful for the manipulation of complex metabolic or regulatory pathways involving multiple genes in Ganoderma.

Gut-derived memory γδ T17 cells exacerbate sepsis-induced acute lung injury in mice.

Sepsis is a critical global health concern linked to high mortality rates, often due to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). While the gut-lung axis involvement in ALI is recognized, direct migration of gut immune cells to the lung remains unclear. Our study reveals sepsis-induced migration of γδ T17 cells from the small intestine to the lung, triggering an IL-17A-dominated inflammatory response in mice. Wnt signaling activation in alveolar macrophages drives CCL1 upregulation, facilitating γδ T17 cell migration. CD44+ Ly6C- IL-7Rhigh CD8low cells are the primary migratory subtype exacerbating ALI. Esketamine attenuates ALI by inhibiting pulmonary Wnt/ß-catenin signaling-mediated migration. This work underscores the pivotal role of direct gut-to-lung memory γδ T17 cell migration in septic ALI and clarifies the importance of localized IL-17A elevation in the lung.