Hydrodynamics and dissolved organic matter components shaped the fate of dissolved heavy metals in an intensely anthropogenically disturbed estuary.

Anthropogenic activities and natural erosion caused abundant influx of heavy metals (HMs) and organic matter (OM) into estuaries characterized by the dynamic environments governed by tidal action and river flow. Similarities and differences in the fate of HM and OM as well as the influences of OM on HMs remain incomplete in estuaries with seasonal human activity and hydrodynamic force. To address this gap, dissolved HMs (dHMs) and fluorescence dissolved OM (FDOM) were investigated in the Pearl River Estuary, a highly seasonally anthropogenic and dynamic estuary. It aimed to elucidate the effects of hydrodynamic conditions and DOM on the seasonal fate of dHMs via the multivariate statistical methods. Our findings indicated dHMs and FDOM exhibited consistently higher levels in the upper estuarine and coastal waters in both seasons, predominantly controlled by the terrestrial/anthropogenic discharge. In the wet season, dHMs and humic-like substances (HULIS) were positively correlated, showing that dHMs readily combined with HULIS. This association led to a synchronous decrease offshore along the axis of the estuary and the transport following the river plume in the surface affected by the salt wedge. Contrarily, dHMs were prone to complex with protein-like components impacted by the hydrodynamics during the dry season. Principal component analysis (PCA) results revealed the terrestrial/anthropogenic inputs and the fresh-seawater mixing process were the most crucial factors responsible for the fate of dHM in wet and dry seasons, respectively, with DOM identified as a secondary but significant influencing factor in both seasons. This study holds significance in providing valuable insights into the migration, transformation, the ultimate fate of dHMs in anthropogenically influenced estuaries, as well as the intricate dynamics governing coastal ecosystems.

miR-940 modulates CD47 to suppress biological functions of lung adenocarcinoma cells.

OBJECTIVE: mir-940 and CD47 play regulatory and immunoregulatory roles in lung cancer. While previous study found that the expression of mir-940 decreased, associated with the increasing of CD47 in lung adenocarcinoma. However, their inherent correlations remain elusive. Herein, this experiment intends to search for the relevant molecular mechanisms regulating the biological function of non-small cell lung cancer. METHODS: The cancer and adjacent tissue samples were collected from 20 pairs of newly diagnosed non-small cell lung cancer patients without applying radiotherapy and chemotherapy. We performed immunohistochemistry containing 45 lung adenocarcinoma tissues to investigate the relationship between the clinicopathological features and CD47 expression. The expressions of mir-940 and CD47 were detected by real-time quantitative polymerase chain reaction (qRT-PCR). Lung epithelial and lung adenocarcinoma (A549, H1299, GLC-82, PC-9) cell lines were cultured to detect the expression of mir-940 and CD47 molecules in each cell line. According to the expression situation, 2 cell lines were selected for mimic and siRNA transfection, and the transfection efficiency was also verified by qRT-PCR and western blot. CCK-8, transwell migration, transwell invasion, and colony formation assays were used to detect the changes in biological functions of lung adenocarcinoma cells after transfection, such as enhanced proliferation, migration, invasion, and cloning. The changes of related protein molecules after transfection were detected by western blot. The dual-luciferase experiment verified the targeting regulation relationship between mir-940 and CD47. Finally, flow cytometry analysis of apoptosis and cell cycle were carried out to detect apoptosis cells and change phase of cell cycle distribution. RESULTS: CD47 expression was not associated with clinicopathologic factors in lung adenocarcinoma. The proliferation, migration, invasion, and cloning abilities of lung adenocarcinoma cells were weakened after transfection with mir-940 mimic and siRNA-CD47. Overexpression of CD47 could promote proliferation, migration, invasion, cloning abilities, reduce apoptosis rate and attenuate the antitumor effect of mir-940 on lung adenocarcinoma. Dual luciferase experiments confirmed that mir-940 can target CD47 molecules. CONCLUSION: mir-940 can inhibit the biological function of lung adenocarcinoma cells by targeting CD47.

Effect of respiratory muscle training in patients with stable chronic obstructive pulmonary disease: A systematic review and meta-analysis.

Objectives: Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory disorder characterized by progressive airflow limitation. This meta-analysis aims to evaluate the effectiveness of respiratory muscle training (RMT) on key pulmonary function parameters, inspiratory muscle strength and quality of life in patients with stable COPD. Methods: A comprehensive search was conducted in the databases including PubMed, Cochrane, Web of Science, Embase, and ClinicalTrials.gov, from their inception to June 12, 2023. Randomized controlled trials (RCTs) evaluating the impact of RMT on stable COPD were included for meta-analysis. Results: In total, 12 RCTs involving 453 participants were included in the meta-analysis. RMT demonstrated a significant increase in maximal inspiratory pressure (PImax, MD, 95% CI: 14.34, 8.17 to 20.51, P < 0.001) but not on maximal expiratory pressure (PEmax). No significant improvement was observed in 6-Min walk test (6MWT), dyspnea, forced expiratory volume in 1 s (FEV1), forced vital capacity ratio (FVC) and quality of life between RMT and control groups. However, subgroup analysis revealed a significant negative effect of RMT alone on FEV1/FVC (MD, 95% CI: 2.59, -5.11 to -0.06, P = 0.04). When RMT was combined with other interventions, improvements in FEV1/FVC and FEV1 were found, although not statistically significant. Conclusion: RMT can effectively improve maximal inspiratory pressure in stable COPD patients, but the effect is slight in improving lung function, dyspnea and quality of life. It is recommended to combine with other treatment strategies to comprehensively improve the prognosis of COPD patients.

Design and Analysis of the Dual-Band Far-Field Super-Resolution Metalens with Large Aperture.

The resolving power of metalens telescopes rely on their aperture size. Flat telescopes are advancing with the research on super-resolution confocal metalenses with large aperture. However, the aperture sizes of metalenses are usually bound within hundreds of micrometers due to computational and fabrication challenges, limiting their usage on practical optical devices like telescopes. In this work, we demonstrated a two-step designing method for the design of dual-band far-field super-resolution metalens with aperture sizes from the micro-scale to macro-scale. By utilizing two types of inserted unit cells, the phase profile of a dual-wavelength metalens with a small aperture of 100 µm was constructed. Through numerical simulation, the measured FWHM values of the focal spots of 5.81 µm and 6.81 µm at working wavelengths of 632.8 nm and 1265.6 nm were found to all be slightly smaller than the values of 0.61 λ/NA, demonstrating the super-resolution imaging of the designed metalens. By measuring the optical power ratio of the focal plane and the incident plane, the focusing efficiencies were 76% at 632.8 nm and 64% at 1265.6 nm. Based on the design method for small-aperture metalens, far-field imaging properties through the macro metalens with an aperture of 40 mm were simulated by using the Huygens-Fresnel principle. The simulation results demonstrate confocal far-field imaging behavior at the target wavelengths of 632.8 nm and 1265.6 nm, with a focal length of 200 mm. The design method for dual-band far-field super-resolution metalens with a large aperture opens a door towards the practical applications in the dual-band space telescope system.

DELE1 promotes translation-associated homeostasis, growth, and survival in mitochondrial myopathy.

Mitochondrial dysfunction causes devastating disorders, including mitochondrial myopathy. Here, we identified that diverse mitochondrial myopathy models elicit a protective mitochondrial integrated stress response (mt-ISR), mediated by OMA1-DELE1 signaling. The response was similar following disruptions in mtDNA maintenance, from knockout of Tfam, and mitochondrial protein unfolding, from disease-causing mutations in CHCHD10 (G58R and S59L). The preponderance of the response was directed at upregulating pathways for aminoacyl-tRNA biosynthesis, the intermediates for protein synthesis, and was similar in heart and skeletal muscle but more limited in brown adipose challenged with cold stress. Strikingly, models with early DELE1 mt-ISR activation failed to grow and survive to adulthood in the absence of Dele1, accounting for some but not all of OMA1's protection. Notably, the DELE1 mt-ISR did not slow net protein synthesis in stressed striated muscle, but instead prevented loss of translation-associated proteostasis in muscle fibers. Together our findings identify that the DELE1 mt-ISR mediates a stereotyped response to diverse forms of mitochondrial stress and is particularly critical for maintaining growth and survival in early-onset mitochondrial myopathy.

A better method to evaluate the reliability of echocardiography for assessment of pulmonary hypertension: comparison of tricuspid regurgitant spectrum quality grading and tricuspid valve regurgitation degree.

Background: Transthoracic echocardiography (TTE) is recommended as the most important noninvasive screening tool for the diagnosis of pulmonary hypertension (PH), sonographers usually measure the volume of regurgitant flow rather than evaluating the spectral quality, so physicians will determine whether the ultrasound measurements of pulmonary arterial systolic pressure (US-PASP) are reliable based on the volume of tricuspid regurgitation (TR). Therefore, for the first time, we grade the quality of TR spectrum (TRS) based on its integrity and clarity, aiming to assess clinical application value of different tricuspid regurgitant spectrum quality grades (TR-SQG), and investigate whether the accuracy of US-PASP is more trustworthy than TR. Methods: We retrospectively analyzed 108 patients with chronic thromboembolic PH (CTEPH) to compare the correlation and agreement between US-PASP and right heart catheterization measurements of PASP (RHC-PASP). TR area (TRA) and TRS were measured in each patient, and TR-SQG was performed. Results: The correlation coefficients between US-PASP and RHC-PASP were r=0.622 (P<0.001), r=0.754 (P<0.001), r=0.595 (P<0.001) in mild, moderate, severe TR, and r=0.301 (P=0.135), r=0.747 (P<0.001), r=0.739 (P<0.001), r=0.828 (P<0.001) in TR-SQG I-IV, respectively. Bland-Altman analysis revealed the mean biases of 5.05, 3.06, 7.62 mmHg in mild, moderate, severe TR, and -16.47, -8.07, 1.82, 6.09 mmHg in TR-SQG I-IV, respectively. In mild TR with the TR-SQG III and IV, the correlation coefficients between US-PASP and RHC-PASP were r=0.779 (P<0.001), intraclass correlation coefficient (ICC) =0.774, paired t-test P=0.160, respectively; and the consistency was significantly higher than that of mild TR without considering TR-SQG. In moderate TR with the TR-SQG III and IV, the r=0.749, ICC =0.746, paired t-test P=0.298 between US-PASP and RHC-PASP. Conclusions: The US-PASP with TR-SQG III or IV is trustworthy, and its accuracy and consistency are better than those predicted by the traditional severity of TR. The establishment of the ultrasound evaluation system of TR-SQG helps clinicians to judge whether the US-PASP is accurate, credible, and reliable.

Estuarine hydrodynamic processes driving the molecular changes of terrestrial dissolved organic nitrogen: From mixing to biological modification.

Estuaries receive substantial amounts of terrestrial dissolved organic nitrogen (tDON), which will be transported from the freshwater to the oceanic terminus through vigorous exchange processes. However, the intricate migration and transformation dynamics of tDON during this transportation, particularly at a molecular level, remain constrained. To address this knowledge gap, Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) was used for the analysis of DON molecular composition in the Pearl River Estuary (PRE), a river-dominated estuarine system influenced by intensified anthropogenic activities in southern China. The results showed a pronounced spatial-temporal variation in DON concentration in the study area. At the molecular level, tDON exhibited reduced unsaturation and aromaticity, coupled with an elevated abundance of DON compounds containing one­nitrogen atom (1 N-DON, 53.17 %) and compounds containing carbon, hydrogen, oxygen, nitrogen, and sulfur (CHONS) (27.46 %). It was evident that lignin was depleted while more oxygenated tannin compounds were generated in the freshwater-seawater mixing zone. This transformation is attributed to heightened biological activities, likely influenced by the priming effect of terrestrial nutrient inputs. In summer, the prevailing plume combined with biological activities in the strong mixing area and outer estuary increased the abundance of 3 N-DON molecules and a concurrent rise in the abundance of DON compounds containing only carbon, hydrogen, oxygen, and nitrogen (CHON), DON compounds containing carbon, hydrogen, oxygen, nitrogen, sulfur, and phosphorus (CHONSP), and CHONS. This trend also underscores the expanding role of marine plankton and microbes in the utilization of DON compounds containing carbon, hydrogen, oxygen, nitrogen, and phosphorus (CHONP). These findings provide details of tDON transformation processes at the molecular level in a river-dominated estuary and underline the estuarine hydrodynamics involved in transporting and altering DON within the estuary.

Association between cytomegalovirus seropositivity and all-cause mortality: An original cohort study.

To examine the association between cytomegalovirus (CMV) seropositivity and all-cause mortality in a nationwide cohort of US adults. We obtained data from the National Health and Nutrition Examination Survey III (1988-1994), including 16,547 participants aged 18-90 years old with CMV serology assessments. Mortality status was ascertained until December 2019 using the National Death Index linkage data. The Cox proportional hazard model was applied to estimate the association between CMV seropositivity and mortality. During a median follow-up of 26.3 years, 6,930 deaths were recorded. CMV seropositivity was associated with a higher hazard of all-cause mortality after adjusting for attained age, sex, and ethnicity (HR: 1.22, 95% CI: 1.10, 1.36, p < 0.001). The magnitude of the association attenuated slightly after adjusting further for body mass index, family income, smoking status, diabetes, and self-reported cancer history (HR = 1.11, 95% CI: 1.00, 1.23, p = 0.04). While the association was observed for both men and women, it was only statistically significant among non-Hispanic white people (HR: 1.16, 95% CI: 1.06, 1.26, p = 0.001) but not among other ethnic populations. CMV seropositivity might be an independent risk factor for all-cause mortality among US adults. If the findings are validated in an independent population, further research is needed to unveil the biological mechanisms driving the increased mortality with CMV seropositivity.

Coordinated Transcriptome and Metabolome Analyses of a Barley hvhggt Mutant Reveal a Critical Role of Tocotrienols in Endosperm Starch Accumulation.

Tocotrienols and tocopherols (vitamin E) are potent antioxidants that are synthesized in green plants. Unlike ubiquitous tocopherols, tocotrienols predominantly accumulate in the endosperm of monocot grains, catalyzed by homogentiate geranylgeranyl transferase (HGGT). Previously, we generated a tocotrienol-deficient hvhggt mutant with shrunken barley grains. However, the relationship between tocotrienols and grain development remains unclear. Here, we found that the hvhggt lines displayed hollow endosperms with defective transfer cells and reduced aleurone layers. The carbohydrate and starch contents of the hvhggt endosperm decreased by approximately 20 and 23%, respectively. Weighted gene coexpression network analyses identified a critical gene module containing HvHGGT, which was strongly associated with the hvhggt mutation and enriched with gene functions in starch and sucrose metabolism. Metabolome measurements revealed an elevated soluble sugar content in the hvhggt endosperm, which was significantly associated with the identified gene modules. The hvhggt endosperm had significantly higher NAD(H) and NADP(H) contents and lower levels of ADPGlc (regulated by redox balance) than the wild-type, consistent with the absence of tocotrienols. Interestingly, exogenous α-tocotrienol spraying on developing hvhggt spikes partially rescued starch accumulation and endosperm defects. Our study supports a potential novel function of tocotrienols in grain starch accumulation and endosperm development in monocot crops.

Identification of anthropogenic source of Pb and Cd within two tropical seagrass species in South China: Insight from Pb and Cd isotopes.

Seagrass beds are susceptible to deterioration and heavy metals represent a crucial impact factor. The accumulation of heavy metal in two tropical seagrass species were studied in South China in this study and multiple methods were used to identify the heavy metal sources. E. acoroides (Enhalus acoroides) and T. hemperichii (Thalassia hemperichii) belong to the genus of Enhalus and Thalassia in the Hydrocharitaceae family, respectively. Heavy metal concentrations in the two seagrasses followed the order of Cr > Zn > Cu > Ni > As > Pb > Co > Cd based on the whole plant, and their bioconcentration factors were 31.8 ± 29.3 (Cr), 5.7 ± 1.3 (Zn), 7.0 ± 3.8 (Cu), 3.0 ± 1.9 (Ni), 1.2 ± 0.3 (As), 1.7 ± 0.9 (Pb), 9.1 ± 11.1 (Co) and 2.8 ± 0.6 (Cd), indicating the intense enrichment in Co and Cr within the two seagrasses. The two seagrasses were prone to accumulate all the listed heavy metals (except for As in E. acoroides), especially Co (BCFs of 1124) and Cr (BCFs of 2689) in the aboveground parts, and the belowground parts of both seagrasses also accumulated most metals (BCFs of 27) excluding Co and Pb. The Pb isotopic ratios (mean 208Pb/204Pb, 207Pb/204Pb and 206Pb/204Pb values of 38.2054, 15.5000 and 18.3240, respectively) and Cd isotopic compositions (δ114/110Cd values ranging from -0.09‰ to 0.58‰) within seagrasses indicated the anthropogenic sources of Pb and Cd including coal combustion, traffic emissions and agricultural activities. This study described the absorption characteristics of E. acoroides and T. hemperichii to some heavy metals, and further demonstrated the successful utilization of Pb and Cd isotopes as discerning markers to trace anthropogenic origins of heavy metals (mainly Pb and Cd) in seagrasses. Pb and Cd isotopes can mutually verify and be helpful to understand more information in pollution sources and improve the reliability of conclusion deduced from concentrations or a single isotope.

Photochemically Controlled Release of the Glucose Transporter 1 Inhibitor for Glucose Deprivation Responses and Cancer Suppression Research.

Cancer cells need a greater supply of glucose mainly due to their aerobic glycolysis, known as the Warburg effect. Glucose transport by glucose transporter 1 (GLUT1) is the rate-limiting step for glucose uptake, making it a potential cancer therapeutic target. However, GLUT1 is widely expressed and performs crucial functions in a variety of cells, and its indiscriminate inhibition will cause serious side effects. In this study, we designed and synthesized a photocaged GLUT1 inhibitor WZB117-PPG to suppress the growth of cancer cells in a spatiotemporally controllable manner. WZB117-PPG exhibited remarkable photolysis efficiency and substantial cytotoxicity toward cancer cells under visible light illumination with minimal side effects, ensuring its safety as a potential cancer therapy. Furthermore, our quantitative proteomics data delineated a comprehensive portrait of responses in cancer cells under glucose deprivation, underlining the mechanism of cell death via necrosis rather than apoptosis. We reason that our study provides a potentially reliable cancer treatment strategy and can be used as a spatiotemporally controllable trigger for studying nutrient deprivation-related stress responses.

Bleomycin promotes rAAV2 transduction via DNA-PKcs/Artemis-mediated DNA break repair pathways.

Because it is safe and has a simple genome, recombinant adeno-associated virus (rAAV) is an extremely appealing vector for delivery in in vivo gene therapy. However, its low transduction efficiency for some cells, limits its further application in the field of gene therapy. Bleomycin is a chemotherapeutic agent approved by the FDA whose effect on rAAV transduction has not been studied. In this study, we systematically investigated the effect of Bleomycin on the second-strand synthesis and used CRISPR/CAS9 and RNAi methods to understand the effects of Bleomycin on rAAV vector transduction, particularly the effect of DNA repair enzymes. The results showed that Bleomycin could promote rAAV2 transduction both in vivo and in vitro. Increased transduction was discovered to be a direct result of decreased cytoplasmic rAAV particle degradation and increased second-strand synthesis. TDP1, PNKP, and SETMAR are required to repair the DNA damage gap caused by Bleomycin, TDP1, PNKP, and SETMAR promote rAAV second-strand synthesis. Bleomycin induced DNA-PKcs phosphorylation and phosphorylated DNA-PKcs and Artemis promoted second-strand synthesis. The current study identifies an effective method for increasing the capability and scope of in-vivo and in-vitro rAAV applications, which can amplify cell transduction at Bleomycin concentrations. It also supplies information on combining tumor gene therapy with chemotherapy.

Plant growth and development of tropical seagrass determined rhizodeposition and its related microbial community.

In the recent study, we investigated the seasonal variations in root exudation and microbial community structure in the rhizosphere of seagrass Enhalus acoroides in the South China Sea. We found that the quantity and quality of root exudates varied seasonally, with higher exudation rates and more bioavailable dissolved organic matter (DOM) during the seedling and vegetative stages in spring and summer. Using Illumina NovaSeq sequencing, we analyzed bacterial and fungal communities and discovered that microbial diversity and composition were influenced by root exudate characteristics s and seagrass biomass, which were strongly dependent on seagrass growth stages. Certain bacterial groups, such as Ruegeria, Sulfurovum, Photobacterium, and Ralstonia were closely associated with root exudation and may contribute to sulfur cycling, nitrogen fixation, and carbon remineralization, which were important for plant early development. Similarly, specific fungal taxa, including Astraeus, Alternaria, Rocella, and Tomentella, were enriched in spring and summer and showed growth-promoting abilities. Overall, our study suggests that seagrass secretes different compounds in its exudates at various developmental stages, shaping the rhizosphere microbial assemblages.

Comparing the immune response and protective effect of COVID-19 vaccine under different vaccination strategies.

Although highly infectious respiratory viral infections spread rapidly, humans have evolved a precise and complex immune mechanism to deal with respiratory viruses, with strong intrinsic, highly adaptive and specific humoral and cellular immunity. At the same time, vaccination against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is one of the most cost-effective and efficient means of preventing morbidity, severe illness, and death from Coronavirus disease 2019 (COVID-19). As the global epidemic of COVID-19 continues to evolve and vaccines are being developed, it is important to conduct studies on immunization strategies to optimize vaccination strategies when appropriate. This review was conducted to investigate the relationship between the immune response and the protective effect of different vaccination scenarios (including booster, sequential and hybrid immunity), and to provide a basis for the optimization of vaccination strategies and the development of new vaccines in the future.

Association between cytomegalovirus infection and cancer­related mortality in the US adults.

PURPOSE: In a nationwide cohort of US adults, an exploration of the association between cytomegalovirus (CMV) infection and cancer­related mortality was conducted. MATERIALS AND METHODS: We acquired data from the National Health and Nutrition Examination Survey III (1988-1994), including 11,138 individuals who were aged 18-90 years at enrollment and underwent CMV serology assessments. CMV infection was determined by CMV antibody testing. Cancer­related mortality status was ascertained until December 2019 utilizing the National Death Index linkage data and determined by neoplasms. The Cox proportional hazard model was applied to estimate the potential association between CMV infection and the risk of cancer-related mortality. RESULTS: During a median follow-up of 26.1 years, 1514 cancer­related deaths were identified in the study cohort. After adjusting for age, sex, and ethnicity, CMV infection was associated with a higher hazard of cancer­related mortality (hazard ratio [HR]: 1.39, 95 % CI: 1.13, 1.70). Further adjustments for body mass index, family income, and smoking status slightly attenuated the magnitude of the association (HR: 1.24, 95 % CI: 1.00, 1.53). However, no significant interaction was observed among gender by subgroup analysis. CONCLUSIONS: CMV infection might be an independent risk factor for cancer­related mortality among US adults. Future studies could focus on the mechanisms through which CMV infection influences mortality induced by neoplasms and develop targeted interventions to reduce the risk.

The distinct phases of fresh-seawater mixing intricately regulate the nitrogen transformation processes in a high run-off estuary: Insight from multi-isotopes and microbial function analysis.

Excessive anthropogenic nitrogen inputs lead to the accumulation of nitrogen, and significantly impact the nitrogen transformation processes in estuaries. However, the governing of nitrogen during its transport from terrestrial to estuary under the influence of diverse human activities and hydrodynamic environments, particularly in the fresh-seawater mixing zone, remains insufficient researched and lack of basis. To address this gap, we employed multi-isotopes, including δ15N-NO3-, δ18O-NO3-, δ15N-NH4+, and δ15N-PN, as well as microbial function analysis, to investigate the nitrogen transformation processes in the Pearl River Estuary (PRE), a highly anthropogenic and terrestrial estuary. Principle component analysis (PCA) confirmed that the PRE could clearly partitioned into three zone, e.g., terrestrial area (T zone), mixing area (M zone) and seawater area (S zone), in terms of nitrogen transportation and transformation processes. The δ15N-NO3- (3.38±0.60‰) and δ18O-NO3- (6.35±2.45‰) results in the inner estuary (T area) indicate that NO3-attributed to the domestic sewage and groundwater discharge in the river outlets lead to a higher nitrification rate in the outlets of the Pearl River than in the reaching and seawater intrusion areas, although nitrate is rapidly diluted by seawater after entering the estuary. The transformation of nitrogen in the T zone was under significant nitrogen fixation (0.61 ± 0.22 %) and nitrification processes (0.0043 ± 0.0032 %) (presumably driven by Exiguobacterium sp. (14.1 %) and Cyanobium_PCC-6307 (8.1 %)). In contrast, relatively low δ15N-NO3- (6.83 ± 1.24‰) and high δ18O-NO3- (22.13±6.01‰) imply that atmospheric deposition has increased its contribution to seawater nitrate and denitrification (0.53±0.13 %) was enhanced by phytoplankton/bacterial (such as Psychrobacter sp. and Rhodococcus) in the S zone. The assimilation of NH4 results from the ammonification of NO3- reduces δ15N-NH4+ (5.36 ± 1.49‰) and is then absorbed by particulate nitrogen (PN). The retention of nitrogen when fresh-seawater mixing enhances the elevation of δ15N-NH4+ (8.19 ± 2.19‰) and assimilation of NH4+, leading to an increase in PN and δ15N-PN (6.91 ± 1.52‰) from biological biomass (mainly Psychrobacter sp. and Rhodococcus). The results of this research demonstrate a clear and comprehensive characterization of the nitrogen transformation process in an anthropogenic dominated estuary, highlighting its importance for regulating the nitrogen dissipation in the fresh-seawater mixing process in estuarine ecosystems.

CHCHD10 mutations induce tissue-specific mitochondrial DNA deletions with a distinct signature.

Mutations affecting the mitochondrial intermembrane space protein CHCHD10 cause human disease, but it is not known why different amino acid substitutions cause markedly different clinical phenotypes, including amyotrophic lateral sclerosis-frontotemporal dementia, spinal muscular atrophy Jokela-type, isolated autosomal dominant mitochondrial myopathy and cardiomyopathy. CHCHD10 mutations have been associated with deletions of mitochondrial DNA (mtDNA deletions), raising the possibility that these explain the clinical variability. Here, we sequenced mtDNA obtained from hearts, skeletal muscle, livers and spinal cords of WT and Chchd10 G58R or S59L knockin mice to characterise the mtDNA deletion signatures of the two mutant lines. We found that the deletion levels were higher in G58R and S59L mice than in WT mice in some tissues depending on the Chchd10 genotype, and the deletion burden increased with age. Furthermore, we observed that the spinal cord was less prone to the development of mtDNA deletions than the other tissues examined. Finally, in addition to accelerating the rate of naturally occurring deletions, Chchd10 mutations also led to the accumulation of a novel set of deletions characterised by shorter direct repeats flanking the deletion breakpoints. Our results indicate that Chchd10 mutations in mice induce tissue-specific deletions which may also contribute to the clinical phenotype associated with these mutations in humans.

An analysis of sintilimab combined with ruxolitinib as compassionate therapy for 12 adults with EBV-associated hemophagocytic lymphohistiocytosis.

Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a severe hyperinflammatory illness that affects adults and is caused by an EBV infection. Without allogeneic hematopoietic stem cell transplantation (allo-HSCT), the overall survival of adult patients with EBV-HLH is unsatisfactory, necessitating the development of innovative therapeutic approaches. The clinical records of twelve EBV-HLH patients who received sintilimab therapy combined with ruxolitinib on a compassionate basis at the First Affiliated Hospital of Soochow University were retrospectively examined in this investigation. All the patients responded without fever, but three patients relapsed within a week. Among the nine patients achieving complete response (CR), 55.6% (5/9) maintained CR for >4.5 months, and 33.3% (3/9) relapsed following CR. Neither patients with no response (NR) nor relapsed patients were fit for allo-HSCT, and all died soon after discharge. Six patients had clinical CR with a median follow-up of 5 (4.4-14.7) months. There were no documented severe negative effects. Additional information on this innovative treatment for adult EBV-HLH is provided in our report.

Transcriptional and protein structural characterization of homogentisate phytyltransferase genes in barley, wheat, and oat.

BACKGROUND: Homogentisate phytyltransferase (HPT) is the critical enzyme for the biosynthesis of tocopherols (vitamin E), which are the major lipid-soluble antioxidants and help plants adapt to various stress conditions. HPT is generally strictly conserved in various plant genomes; however, a divergent lineage HPT2 was identified recently in some Triticeae species. The molecular function and transcriptional profiles of HPT2 remain to be characterized. RESULTS: In this study, we performed comprehensive transcriptome data mining of HPT1 and HPT2 in different tissues and stages of barley (Hordeum vulgare), wheat (Triticum aestivum), and oat (Avena sativa), followed by qRT-PCR experiments on HPT1 and HPT2 in different tissues of barley and wheat. We found that the common HPT1 genes (HvHPT1, TaHPT1s, and AsHPT1s) displayed a conserved transcriptional pattern in the three target species and were universally transcribed in various tissues, with a notable preference in leaf. In contrast, HPT2 genes (HvHPT2, TaHPT2, and AsHPT2) were specifically transcribed in spike (developmentally up-regulated) and shoot apex tissues, displaying a divergent tissue-specific pattern. Cis-regulatory elements prediction in the promoter region identified common factors related to light-, plant hormone-, low temperature-, drought- and defense- responses in both HPT1s and HPT2s. We observed the transcriptional up-regulation of HvHPT1 and HvHPT2 under various stress conditions, supporting their conserved function in environmental adaption. We detected a clear, relaxed selection pressure in the HPT2 lineage, consistent with the predicted evolution pattern following gene duplication. Protein structural modelling and substrate docking analyses identified putative catalytic amino acid residues for HvHPT1 and HvHPT2, which are strictly conserved and consistent with their function in vitamin E biosynthesis. CONCLUSIONS: We confirmed the presence of two lineages of HPT in Triticeae and Aveninae, including hexaploid oat, and characterized their transcriptional profiles based on transcriptome and qRT-PCR data. HPT1s were ubiquitously transcribed in various tissues, whilst HPT2s were highly expressed in specific stages and tissue. The active transcription of HPT2s, together with its conserved cis-elements and protein structural features, support HPT2s' role in tocopherol production in Triticeae. This study is the first protein structural analysis on the membrane-bound plant HPTs and provides valuable insights into its catalytic mechanism.