Nynrin preserves hematopoietic stem cell function by inhibiting the mitochondrial permeability transition pore opening.

Mitochondria are key regulators of hematopoietic stem cell (HSC) homeostasis. Our research identifies the transcription factor Nynrin as a crucial regulator of HSC maintenance by modulating mitochondrial function. Nynrin is highly expressed in HSCs under both steady-state and stress conditions. The knockout Nynrin diminishes HSC frequency, dormancy, and self-renewal, with increased mitochondrial dysfunction indicated by abnormal mPTP opening, mitochondrial swelling, and elevated ROS levels. These changes reduce HSC radiation tolerance and promote necrosis-like phenotypes. By contrast, Nynrin overexpression in HSCs diminishes irradiation (IR)-induced lethality. The deletion of Nynrin activates Ppif, leading to overexpression of cyclophilin D (CypD) and further mitochondrial dysfunction. Strategies such as Ppif haploinsufficiency or pharmacological inhibition of CypD significantly mitigate these effects, restoring HSC function in Nynrin-deficient mice. This study identifies Nynrin as a critical regulator of mitochondrial function in HSCs, highlighting potential therapeutic targets for preserving stem cell viability during cancer treatment.

Neoadjuvant chemotherapy with or without camrelizumab in resectable esophageal squamous cell carcinoma: the randomized phase 3 ESCORT-NEO/NCCES01 trial.

Recent single-arm studies involving neoadjuvant camrelizumab, a PD-1 inhibitor, plus chemotherapy for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) have shown promising results. This multicenter, randomized, open-label phase 3 trial aimed to further assess the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy followed by adjuvant camrelizumab, compared to neoadjuvant chemotherapy alone. A total of 391 patients with resectable thoracic LA-ESCC (T1b-3N1-3M0 or T3N0M0) were stratified by clinical stage (I/II, III or IVA) and randomized in a 1:1:1 ratio to undergo two cycles of neoadjuvant therapy. Treatments included camrelizumab, albumin-bound paclitaxel and cisplatin (Cam+nab-TP group; n = 132); camrelizumab, paclitaxel and cisplatin (Cam+TP group; n = 130); and paclitaxel with cisplatin (TP group; n = 129), followed by surgical resection. Both the Cam+nab-TP and Cam+TP groups also received adjuvant camrelizumab. The dual primary endpoints were the rate of pathological complete response (pCR), as evaluated by a blind independent review committee, and event-free survival (EFS), as assessed by investigators. This study reports the final analysis of pCR rates. In the intention-to-treat population, the Cam+nab-TP and Cam+TP groups exhibited significantly higher pCR rates of 28.0% and 15.4%, respectively, compared to 4.7% in the TP group (Cam+nab-TP versus TP: difference 23.5%, 95% confidence interval (CI) 15.1-32.0, P < 0.0001; Cam+TP versus TP: difference 10.9%, 95% CI 3.7-18.1, P = 0.0034). The study met its primary endpoint of pCR; however, EFS is not yet mature. The incidence of grade ≥3 treatment-related adverse events during neoadjuvant treatment was 34.1% for the Cam+nab-TP group, 29.2% for the Cam+TP group and 28.8% for the TP group; the postoperative complication rates were 34.2%, 38.8% and 32.0%, respectively. Neoadjuvant camrelizumab plus chemotherapy demonstrated superior pCR rates compared to chemotherapy alone for LA-ESCC, with a tolerable safety profile. Chinese Clinical Trial Registry identifier: ChiCTR2000040034 .

Efficacy of acupuncture in refractory irritable bowel syndrome patients: a randomized controlled trial.

Previous studies have confirmed that acupuncture for irritable bowel syndrome (IBS) provided an additional benefit over usual care alone. Therefore, we performed a multicenter, randomized, sham-controlled trial to assess the efficacy and safety of acupuncture versus sham acupuncture for refractory IBS in patients in the context of conventional treatments. Patients in the acupuncture and sham acupuncture groups received real or sham acupuncture treatment in 3 sessions per week for a total of 12 sessions. The primary outcome was a change in the IBS-Symptom Severity Scale (IBS-SSS) score from baseline to week 4. A total of 521 participants were screened, and 170 patients (85 patients per group) were enrolled and included in the intention-to-treat analysis. Baseline characteristics were comparable across the two groups. From baseline to 4 weeks, the IBS-SSS total score decreased by 140.0 (95% CI: 126.0 to 153.9) in the acupuncture group and 64.4 (95% CI: 50.4 to 78.3) in the sham acupuncture group. The between-group difference was 75.6 (95% CI: 55.8 to 95.4). Acupuncture efficacy was maintained during the 4-week follow-up period. There were no serious adverse events. In conclusion, acupuncture provided benefits when combined with treatment as usual, providing more options for the treatment of refractory IBS.

Electric Field-Enhanced Ion Rejection Rate in Freeze Desalination.

Freeze desalination is an appealing method for seawater desalination through freezing seawater. The percentage of ions in the liquid phase, which is termed ion rejection rate, is a critical factor affecting the performance of freeze desalination. Improving the ion rejection rate is an important topic for freeze desalination. In this work, we investigate the effects of electric fields on the ion rejection rate during the freezing of seawater through molecular dynamics simulations.  It is found that the ion rejection rate increases with increasing electric field strength.  The enhanced ion rejection rate is due to the reduction of the energy barrier at the ice-water interface caused by the electric field, which affects the orientation of water molecules and ion-water interactions. However, the electric field hinders the ice growth rate, which affects the productivity of freeze desalination. Nevertheless, the finding in this work offers a new idea to improve the ion rejection rate. Practically, a trade-off needs to be found to optimize the overall performance of freeze desalination.

An efficient and high-water-content enzymatic esterification method for the synthesis of ß-sitosterol conjugated linoleate via a sodium citrate-based three-liquid-phase system.

Three-liquid-phase systems (TLPSs) are novel interfacial enzymatic reaction systems that have been successfully applied in many valuable reactions. However, these systems are suitable only for hydrolysis reactions and not for more widely used esterification reactions. Surprisingly, our recent research revealed that two water-insoluble substrates (ß-sitosterol and conjugated linoleic acid) could be rapidly esterified in this system. The initial rate of the esterification reaction in the TLPS based on sodium citrate was enhanced by approximately 10-fold relative to that in a traditional water/n-hexane system. The special emulsion structure (S/W1/W2 emulsion) formed may be vital because it not only provides a larger reaction interface but also spontaneously generates a middle phase that might regulate water activity to facilitate esterification. Furthermore, the lipase-enriched phase could be reused at least 8 times without significant loss of catalytic efficiency. Therefore, this TLPS is an ideal enzymatic esterification platform for ester synthesis because it is efficient, convenient to use, and cost-effective.

RNA Helicase DDX5 Maintains Cardiac Function by Regulating CamkIIδ Alternative Splicing.

BACKGROUND: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. RNA-binding proteins are identified as regulators of cardiac disease; DDX5 (dead-box helicase 5) is a master regulator of many RNA processes, although its function in heart physiology remains unclear. METHODS: We assessed DDX5 expression in human failing hearts and a mouse HF model. To study the function of DDX5 in heart, we engineered cardiomyocyte-specific Ddx5 knockout mice. We overexpressed DDX5 in cardiomyocytes using adeno-associated virus serotype 9 and performed transverse aortic constriction to establish the murine HF model. The mechanisms underlined were subsequently investigated using immunoprecipitation-mass spectrometry, RNA-sequencing, alternative splicing analysis, and RNA immunoprecipitation sequencing. RESULTS: We screened transcriptome databases of murine HF and human dilated cardiomyopathy samples and found that DDX5 was significantly downregulated in both. Cardiomyocyte-specific deletion of Ddx5 resulted in HF with reduced cardiac function, an enlarged heart chamber, and increased fibrosis in mice. DDX5 overexpression improved cardiac function and protected against adverse cardiac remodeling in mice with transverse aortic constriction-induced HF. Furthermore, proteomics revealed that DDX5 is involved in RNA splicing in cardiomyocytes. We found that DDX5 regulated the aberrant splicing of Ca2+/calmodulin-dependent protein kinase IIδ (CamkIIδ), thus preventing the production of CaMKIIδA, which phosphorylates L-type calcium channel by serine residues of Cacna1c, leading to impaired Ca2+ homeostasis. In line with this, we found increased intracellular Ca2+ transients and increased sarcoplasmic reticulum Ca2+ content in DDX5-depleted cardiomyocytes. Using adeno-associated virus serotype 9 knockdown of CaMKIIδA partially rescued the cardiac dysfunction and HF in Ddx5 knockout mice. CONCLUSIONS: These findings reveal a role for DDX5 in maintaining calcium homeostasis and cardiac function by regulating alternative splicing in cardiomyocytes, identifying the DDX5 as a potential target for therapeutic intervention in HF.

Novel insights into immune cells modulation of tumor resistance.

Tumor resistance poses a significant challenge to effective cancer treatment, making it imperative to explore new therapeutic strategies. Recent studies have highlighted the profound involvement of immune cells in the development of tumor resistance. Within the tumor microenvironment, macrophages undergo polarization into the M2 phenotype, thus promoting the emergence of drug-resistant tumors. Neutrophils contribute to tumor resistance by forming extracellular traps. While T cells and natural killer (NK) cells exert their impact through direct cytotoxicity against tumor cells. Additionally, dendritic cells (DCs) have been implicated in preventing tumor drug resistance by stimulating T cell activation. In this review, we provide a comprehensive summary of the current knowledge regarding immune cell-mediated modulation of tumor resistance at the molecular level, with a particular focus on macrophages, neutrophils, DCs, T cells, and NK cells. The targeting of immune cell modulation exhibits considerable potential for addressing drug resistance, and an in-depth understanding of the molecular interactions between immune cells and tumor cells holds promise for the development of innovative therapies. Furthermore, we explore the clinical implications of these immune cells in the treatment of drug-resistant tumors. This review emphasizes the exploration of novel approaches that harness the functional capabilities of immune cells to effectively overcome drug-resistant tumors.

Multicentre randomized clinical trial on robot-assisted versus video-assisted thoracoscopic oesophagectomy (REVATE trial).

BACKGROUND: Surgery for oesophageal squamous cell carcinoma involves dissecting lymph nodes along the recurrent laryngeal nerve. This is technically challenging and injury to the recurrent laryngeal nerve may lead to vocal cord palsy, which increases the risk of pulmonary complications. The aim of this study was to compare the efficacy and safety of robot-assisted oesophagectomy (RAO) versus video-assisted thoracoscopic oesophagectomy (VAO) for dissection of lymph nodes along the left RLN. METHODS: Patients with oesophageal squamous cell carcinoma who were scheduled for minimally invasive McKeown oesophagectomy were allocated randomly to RAO or VAO, stratified by centre. The primary endpoint was the success rate of left recurrent laryngeal nerve lymph node dissection. Success was defined as the removal of at least one lymph node without causing nerve damage lasting longer than 6 months. Secondary endpoints were perioperative and oncological outcomes. RESULTS: From June 2018 to March 2022, 212 patients from 3 centres in Asia were randomized, and 203 were included in the analysis (RAO group 103; VAO group 100). Successful left recurrent laryngeal nerve lymph node dissection was achieved in 88.3% of the RAO group and 69% of the VAO group (P < 0.001). The rate of removal of at least one lymph node according to pathology was 94.2% for the RAO and 86% for the VAO group (P = 0.051). At 1 week after surgery, the RAO group had a lower incidence of left recurrent laryngeal nerve palsy than the VAO group (20.4 versus 34%; P = 0.029); permanent recurrent laryngeal nerve palsy rates at 6 months were 5.8 and 20% respectively (P = 0.003). More mediastinal lymph nodes were dissected in the RAO group (median 16 (i.q.r. 12-22) versus 14 (10-20); P = 0.035). Postoperative complication rates were comparable between the two groups and there were no in-hospital deaths. CONCLUSION: In patients with oesophageal squamous cell carcinoma, RAO leads to more successful left recurrent laryngeal nerve lymph node dissection than VAO, including a lower rate of short- and long-term recurrent laryngeal nerve injury. Registration number: NCT03713749 (http://www.clinicaltrials.gov).

Oesophageal cancer often requires complex surgery. Recently, minimally invasive techniques like robot- and video-assisted surgery have emerged to improve outcomes. This study compared robot- and video-assisted surgery for oesophageal cancer, focusing on removing lymph nodes near a critical nerve. Patients with a specific oesophageal cancer type were assigned randomly to robot- or video-assisted surgery at three Asian hospitals. Robot-assisted surgery had a higher success rate in removing lymph nodes near the important nerve without permanent damage. It also had shorter operating times, more lymph nodes removed, and faster drain removal after surgery. In summary, for oesophageal cancer surgery, the robotic approach may provide better lymph node removal and less nerve injury than video-assisted techniques.

Anthropogenic shrub encroachment has accelerated the degradation of desert steppe soil over the past four decades.

Anthropogenic and natural shrub encroachment have similar ecological consequences on native grassland ecosystems. In fact, there is an accelerating trend toward anthropogenic shrub encroachment, as opposed to the century-long process of natural shrub encroachment. However, the soil quality during the transition of anthropogenic shrub encroachment into grasslands remains insufficiently understood. Here, we used a soil quality assessment method that utilized three datasets and two scoring methods to evaluate changes in soil quality during the anthropogenic transition from temperate desert grassland to shrubland. Our findings demonstrated that the soil quality index decreased with increasing shrub cover, from 0.49 in the desert grassland to 0.31 in the shrubland. Our final results revealed a gradual and significant decline of 36.73 % in soil quality during the transition from desert grassland to shrubland. Reduced soil moisture levels, nutrient availability, and microbial activity characterized this decline. Nearly four decades of anthropogenic shrub encroachment have exacerbated soil drought conditions while leading to a decrease in perennial herbaceous plants and an increase in bare ground cover; these factors can explain the observed decline in soil quality. These findings emphasize the importance of considering soil moisture availability and potential thresholds when implementing revegetation strategies in arid and semiarid regions.

The Main Failure Modes of Hot-Work Die Steel and the Development Status of Traditional Strengthening Methods and Nano-Strengthening Technology.

As an important part of die steels, hot-work die steels are mainly used to manufacture molds made of solid metal or high-temperature liquid metal from heating to recrystallization temperature. In view of the requirements for mechanical properties and service life for hot-work die steel, it is conducive to improve the thermal fatigue resistance, wear resistance, and oxidation resistance of hot work die steel. In this review, the main failure modes of hot-work die steel were analyzed. Four traditional methods of strengthening and toughening die steel were summarized, including optimizing alloying elements, electroslag remelting, increasing the forging ratio, and heat treatment process enhancement. A new nano-strengthening method was introduced that aimed to refine the microstructure of hot-work abrasive steel and improve its service performance by adding nanoparticles into molten steel to achieve uniform dispersion. This review provides an overview to improve the service performance and service life of hot work die steel.

Anti-inflammatory effects and beneficial effects of the feed additive Urtica cannabina L. in zebrafish.

Urtica cannabina L. (UL) has been used clinically for centuries because of its anti-inflammatory properties. This study aimed to investigate the underlying mechanisms and anti-inflammatory effects of different UL concentrations in zebrafish. To elucidate UL's anti-inflammatory properties, two inflammation zebrafish models were designed 1) by severing the zebrafish's caudal fin to assess the repairing effect of UL on the tail inflammation, and 2) by inducing lipopolysaccharides (LPS)-mediated intestinal inflammation to assess the protective and reparative effects of UL on intestinal inflammation at the histological and genetic levels. Furthermore, the effect of UL on the LPS-induced intestinal flora changes was also assessed. After caudal fin resection, a scar formed on the tail of the zebrafish, and the area of the caudal fin increased by 1.30 times as much as that of the control group (P < 0.01). Moreover, this tail scar was alleviated after 10 mg/g UL supplementation but not after 30 mg/g UL dose. LPS decreased the feed intake and body weight of the zebrafish; however, these effects were reversed after 10 and 30 mg/g doses of UL. In addition, the LPS treatment also reduced the intestinal goblet cells by 49% in the zebrafish when compared with the control, which was significantly restored after 10 and 30 mg/g UL treatments. At the genetics level, the expression of the pro-inflammatory cytokine genes (TNF-α, IL6, and IL8) showed that 10 and 30 mg/g UL doses could rescue LPS-induced expression. The gut microbiota analysis revealed changes in the abundance of four major bacterial phyla in the 10 and 30 mg/g UL-treated groups, with an increased probiotic Bacteroidota and decreased pathogenic bacteria. These results indicate that UL strongly inhibits inflammation caused by caudal fin removal and LPS-induced inflammatory changes in the zebrafish intensity, suggesting that UL is a feed additive that could be developed to improve resistance to inflammation in livestock.

Analysis on the minimum structure of harmonic spectra from MgO crystals.

Recent theoretical and experimental findings have demonstrated the minimum characteristic in the harmonic spectrum of bulk MgO crystals subjected to intense laser pulses. However, the dominant mechanism behind this minimum structure is still under debate. This study simulates the harmonic spectrum from a MgO crystal in a linearly polarized laser pulse by solving multi-band semiconductor Bloch equations. The results show that the minimum feature at 20 eV in the MgO harmonic spectra from 1700 and 800 nm laser pulses is due to band dispersion and interference between interband harmonics. Notably, the disappearance of the minimum structure at 14 eV in the harmonic spectrum from the 800 nm laser is attributed to the intensity suppression of higher energy harmonics, caused by decreased electron population at the boundary of the first Brillouin zone in the multi-band case. These findings offer insights into the spectral structure of solid-state harmonics, contributing to the all-optical reconstruction of the crystal band based on its harmonic spectrum.

Drag on nanoparticles in a liquid: from slip to stick boundary conditions.

Stokes' law with stick boundary conditions has been widely accepted for the transport of microscale particles in a liquid. For nanoparticles, however, the hydrodynamic boundary conditions become unclear. In this work, the drag force acting on nanoparticles suspended in a liquid and the hydrodynamic boundary coefficient were calculated by using molecular dynamics simulations. For weak interfacial couplings, slip boundary conditions can be used to describe the particle transport, whereas at strong interfacial couplings, the hydrodynamic boundary coefficient converges to a value greater than the prediction by Stokes' law. In the present paper, we propose a density accumulation length to determine the effective particle size, which makes Stokes' law valid for nanoparticles. For a copper nanoparticle suspended in an argon liquid, the density accumulation length increases to 0.32 nm with increasing solid-liquid coupling strength. Furthermore, it is found that there exists a transition from slip to stick boundary conditions as the solid-liquid intermolecular coupling strength increases. The results presented in this work provide guidance for the prediction and manipulation of the transport properties of nanoparticles in a liquid.

Post-transcriptional regulation of DEAD-box RNA helicases in hematopoietic malignancies.

Hematopoiesis represents a meticulously regulated and dynamic biological process. Genetic aberrations affecting blood cells, induced by various factors, frequently give rise to hematological tumors. These instances are often accompanied by a multitude of abnormal post-transcriptional regulatory events, including RNA alternative splicing, RNA localization, RNA degradation, and storage. Notably, post-transcriptional regulation plays a pivotal role in preserving hematopoietic homeostasis. The DEAD-Box RNA helicase genes emerge as crucial post-transcriptional regulatory factors, intricately involved in sustaining normal hematopoiesis through diverse mechanisms such as RNA alternative splicing, RNA modification, and ribosome assembly. This review consolidates the existing knowledge on the role of DEAD-box RNA helicases in regulating normal hematopoiesis and underscores the pathogenicity of mutant DEAD-Box RNA helicases in malignant hematopoiesis. Emphasis is placed on elucidating both the positive and negative contributions of DEAD-box RNA helicases within the hematopoietic system.

Association between gait video information and general cardiovascular diseases: a prospective cross-sectional study.

Aims: Cardiovascular disease (CVD) may not be detected in time with conventional clinical approaches. Abnormal gait patterns have been associated with pathological conditions and can be monitored continuously by gait video. We aim to test the association between non-contact, video-based gait information and general CVD status. Methods and results: Individuals undergoing confirmatory CVD evaluation were included in a prospective, cross-sectional study. Gait videos were recorded with a Kinect camera. Gait features were extracted from gait videos to correlate with the composite and individual components of CVD, including coronary artery disease, peripheral artery disease, heart failure, and cerebrovascular events. The incremental value of incorporating gait information with traditional CVD clinical variables was also evaluated. Three hundred fifty-two participants were included in the final analysis [mean (standard deviation) age, 59.4 (9.8) years; 25.3% were female]. Compared with the baseline clinical variable model [area under the receiver operating curve (AUC) 0.717, (0.690-0.743)], the gait feature model demonstrated statistically better performance [AUC 0.753, (0.726-0.780)] in predicting the composite CVD, with further incremental value when incorporated with the clinical variables [AUC 0.764, (0.741-0.786)]. Notably, gait features exhibited varied association with different CVD component conditions, especially for peripheral artery disease [AUC 0.752, (0.728-0.775)] and heart failure [0.733, (0.707-0.758)]. Additional analyses also revealed association of gait information with CVD risk factors and the established CVD risk score. Conclusion: We demonstrated the association and predictive value of non-contact, video-based gait information for general CVD status. Further studies for gait video-based daily living CVD monitoring are promising.

Association between dietary inflammatory index and fecal incontinence in American adults: a cross-sectional study from NHANES 2005-2010.

Objective: Recent studies have demonstrated that the Dietary Inflammatory Index (DII) is relevant to abnormal gut health. However, there is a lack of studies that have explicitly explored the link between fecal incontinence (FI) and DII. The current study aims to explore the relationship between DII and FI. Methods: The cross-sectional study enrolled a total of 11,747 participants aged 20-85 from NHANES 2005-2010. Weighted logistic regression was conducted to evaluate the relationship between DII and FI, and restricted cubic spline (RCS) was employed to assess the dose-response relationship between DII and FI. Subgroup analyses were performed according to age, gender, race, and BMI. Result: DII levels were found to be significantly higher in patients with FI than in the normal population (p = 0.016). After adjusting for all covariates, DII was found to be significantly correlated with FI (model 2: Q4 vs. Q1, OR = 1.49, 95% CI: 1.04-2.14, p = 0.032, p for trend = 0.039). The dose-response curve revealed that there was no non-linear correlation between DII and FI (p-non-linear = 0.234). Subsequent subgroup analyses uncovered that DII was notably associated with FI in the old (Q4 vs. Q1, OR = 1.84, 95% CI: 1.07-3.18, p = 0.030), female (Q4 vs. Q1: OR = 2.02, 95% CI: 1.23-3.33, p = 0.008), non-Hispanic white (Q4 vs. Q1: OR = 1.70, 95% CI: 1.12-2.59, p = 0.015) populations. Conclusion: DII was positively associated with FI, particularly among old, female and non-Hispanic white individuals. Decreasing daily dietary inflammatory levels may be an effective tactic to prevent FI, but the precise mechanisms need to be further investigated.

The correlation analysis between incisal guidance angle and occlusal plane angles and temporomandibular joint morphology.

OBJECTIVES: The correlations between the incisal guidance angle (IGA) and occlusal plane angles and temporomandibular joint (TMJ) morphology were investigated in adults with skeletal Class II division II malocclusion. MATERIALS AND METHODS: CBCT images of 37 patients were analyzed. It included 19 cases of skeletal Class II division II malocclusion with low angle (study group) and 18 cases of skeletal Class I average angle (control group). The Invivo Dental 5 software was employed to acquire the data of the incisal guidance angle (IGA), occlusal plane angle (FH-OP), anterior occlusal plane angle (FH-AOP) and the TMJ measurement items. RESULTS: The results of IGA, FH-AOP angle and FH-OP angle showed the study group > the control group (P < 0.05). There were statistically difference in the condylar mediolateral diameters, articular eminence inclination and height, and posterior joint spaces between two groups. No differences were revealed in the condylar anteroposterior diameters, the condylar inclination angle, condylar head width and height, condylar length, glenoid fossa depth and width between two groups. In the study group, IGA showed a moderate correlation with FH-AOP, a weak correlation with FH-OP and condylar mediolateral diameters. Meanwhile, there was a correlation between FH-AOP, FH-OP, and TMJ indicators. CONCLUSIONS: The IGA was not only related to FH-AOP and FH-OP, but also to the condylar mediolateral diameters. In addition, there was a correlation between the occlusal plane angles and TMJ morphology in skeletal Class II division II low angle malocclusion. CLINICAL RELEVANCE: For patients with skeletal Class II division II low angle malocclusion, adjusting the IGA and the occlusal plane angles could improve the esthetic appearance of the anterior teeth, occlusal function, and TMJ morphology.

Clinical Characteristics of Peripheral Lymphocyte Subtypes in Chronic Active Epstein-Barr Virus Infection.

BACKGROUND: We aimed to analyze the clinical characteristics of peripheral Epstein-Barr virus (EBV)-infected lymphocyte subtypes in children with chronic active EBV infection (CAEBV). METHODS: The levels of peripheral EBV infection of CD4+ T cells, CD8+ T cells, and CD56+ natural killer (NK) cells were determined by flow cytometry and quantitative polymerase chain reaction (qPCR) in patients with CAEBV from July 2017 to July 2022. RESULTS: In total, 112 children with CAEBV were evaluated. Of these, CD4+ type, CD8+ type, and CD56+ type were defined in 44, 21, and 47 patients, respectively. Patients with CD8+ T-cell type had a significantly higher frequency of rash, while hepatomegaly was more common in patients with CD4+ T-cell type. Generally, patients with CD8+ T-cell type had the lowest overall survival rate (P = .017). Patients treated with chemotherapy and hematopoietic stem cell transplantation (HSCT) had a better prognosis (P = .001). In multivariate analysis, rash, hemophagocytic lymphohistiocytosis, CD8+ T-cell type, and no decrease of plasma EBV-DNA after treatment were independent indicators of poor prognosis (P = .002, .024, .022, and .012, respectively). CONCLUSIONS: In children with CAEBV, rash was more frequent in patients with CD8+ T-cell type, whereas patients with CD4+ T-cell type were more likely to develop hepatomegaly. Patients with CD8+ T-cell type had a poor prognosis despite receiving chemotherapy or further HSCT.

Characteristics of disinfection byproducts from dissolved organic matter during chlor(am)ination of source water in Tibetan Plateau, China.

The Tibetan Plateau, a typical high-altitude area, is less affected by human activities such as industrial development, and the external pollution to water sources is extremely low. Then it is also an important source of water samples for exploring the molecular characteristics of precursors in the dissolved organic matter (DOM) of disinfection byproducts (DBPs) in drinking water. Research data on DBPs in drinking water on the Tibet Plateau remains insufficient, leading to uncertainty about DBP contamination in the area. This study explores the formation potential of 35 typical DBPs, including 6 trihalomethanes (THMs), 9 haloacetic acids (HAAs), 2 halogenated ketones (HKs), 9 nitrosamines (NAs), and 9 aromatic DBPs, during chlorination and chloramination of typical source water samples in the Tibet Plateau of China. Moreover, in order to further investigate the characteristics of the generation of DBPs, the molecular composition of DOM in the collected water samples was characterized by Fourier transform ion cyclotron resonance mass spectrometry. The findings reveal that, for chlorination and chloramination, the average concentration of the five classes of DBPs was ranked as follows (chlorination, chloramination): HAAs (268.1 µg/L, 54.2 µg/L) > THMs (44.0 µg/L, 2.0 µg/L) > HKs (0.7 µg/L, 1.8 µg/L) > NAs (26.5 ng/L, 74.6 ng/L) > Aromatics (20.4 ng/L, 19.5 ng/L). The dominant compounds in THMs, HAAs, and NAs are trichloromethane, dichloroacetic acid, trichloroacetic acid, and nitrosopyrrolidine, respectively. This study highlights a significant positive correlation between DBP generation and UV254, SUV254, and the double bond equivalents of DOM in the source water. It systematically elucidates DOM molecular composition characteristics and DBP formation potential in high-altitude water sources, shedding light on key factors influencing DBP generation at the molecular level in high-altitude areas.

Enhanced hypoxanthine utilization for cAMP salvage synthesis efficiently by Arthrobacter sp. CCTCC 2013431 via xanthine oxidase inhibition.

When hypoxanthine was utilized as the activator for the salvage pathway in cAMP synthesis, xanthine oxidase would generate in quantity leading to low hypoxanthine conversion ratios and cell viability. To enhance cAMP salvage synthesis, fermentations with citrate/luteolin and hypoxanthine coupling added were conducted in a 7 L bioreactor and then multiple physiological indicators of fermentation with luteolin addition were assayed. Due to hypoxanthine feeding, cAMP productivity reached 0.066 g/(L·h) with 43.5% higher than control, however, cAMP synthesis, cell growth and glucose uptake all ceased at 50 h which was shortened by 22 h in comparison to control. The addition of citrate resulted in the cessation of fermentation at 61 h, on the contrary, owing to luteolin addition, cAMP fermentation performance was enhanced significantly during the whole fermentation period (72 h) with higher hypoxanthine conversion ratios and cAMP contents when compared with citrate and only hypoxanthine added batches. Multiple physiological indicators revealed that luteolin inhibited xanthine oxidase activity reducing hypoxanthine decomposition and ROS generation. ATP/AMP, NADH/NAD+ and NADPH/NADP+ were significantly increased especially at the late phase. Moreover, HPRT, PUP expression contents and corresponding gene transcription levels were also elevated. Luteolin could inhibit xanthine oxidase activity and further decrease hypoxanthine decomposition and ROS generation leading to higher hypoxanthine conversion and less cell damage for cAMP salvage synthesis efficiently.