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Abstract Background Methylmalonic aciduria (MMA) is a group of rare genetic metabolic disorders resulting from defects in methylmalonyl coenzyme A mutase (MCM) or intracellular cobalamin (cbl) metabolism. MMA patients show diverse clinical and genetic features across different subtypes and populations. Methods We retrospectively recruited 60 MMA patients from a single center and diagnosed them based on their clinical manifestations and biochemical assays. We then performed genetic analysis to confirm the diagnosis and identify the causal variants. Results We confirmed the common clinical manifestations of MMA reported previously. We also described four rare MMA cases with unusual symptoms or genetic variants, such as pulmonary hypertension or limb weakness in late-onset patients. We identified 15 MMACHC and 26 MMUT variants in 57 patients, including 6 novel MMUT variants. Two patients had only one MMAA variant each, and one patient had mild MMA due to mitochondrial DNA depletion syndrome caused by a SUCLA2 variant. Among 12 critically ill patients, isolated MMA was associated with higher C3, blood ammonia, and acidosis, while combined MMA was linked to hydrocephalus on skull MRI. MMACHC c.658-660delAAG and MMUT c.1280G > A variants were correlated with more severe phenotypes. Conclusions Our study demonstrates the clinical and genotypic heterogeneity of MMA patients and indicates that metabolic screening and genetic analysis are useful tools to identify rare cases.

Abstract Background The genus Sulfitobacter, a member of the family Roseobacteraceae, is widely distributed in the ocean and is believed to play crucial roles in the global sulfur cycle. However, gene clusters associated with sulfur oxidation in genomes of the type strains of this genus have been poorly studied. Furthermore, taxonomic errors have been identified in this genus, potentially leading to significant confusion in ecological and evolutionary interpretations in subsequent studies of the genus Sulfitobacter. This study aims to investigate the taxonomic status of this genus and explore the metabolism associated with sulfur oxidation. Results This study suggests that Sulfitobacter algicola does not belong to Sulfitobacter and should be reclassified into a novel genus, for which we propose the name Parasulfitobacter gen. nov., with Parasulfitobacter algicola comb. nov. as the type species. Additionally, enzymes involved in the sulfur oxidation process, such as the sulfur oxidization (Sox) system, the disulfide reductase protein family, and the sulfite dehydrogenase (SoeABC), were identified in almost all Sulfitobacter species. This finding implies that the majority of Sulfitobacter species can oxidize reduced sulfur compounds. Differences in the modular organization of sox gene clusters among Sulfitobacter species were identified, along with the presence of five genes with unknown function located in some of the sox gene clusters. Lastly, this study revealed the presence of the demethylation pathway and the cleavage pathway used by many Sulfitobacter species to degrade dimethylsulfoniopropionate (DMSP). These pathways enable these bacteria to utilize DMSP as important source of sulfur and carbon or as a defence strategy. Conclusions Our findings contribute to interpreting the mechanism by which Sulfitobacter species participate in the global sulfur cycle. The taxonomic rearrangement of S. algicola into the novel genus Parasulfitobacter will prevent confusion in ecological and evolutionary interpretations in future studies of the genus Sulfitobacter.

Abstract To investigate the relationship between serum uric acid level and glomerular ischemic lesions (GIL) in patients with primary membranous nephropathy (PMN) and identify relevant risk factors. A total of 201 patients with PMN but normal renal function confirmed by renal biopsy executed in the Liaocheng People’s Hospital, China, during January 2020-January 2023 were analyzed retrospectively. The enrolled patients were divided into a hyperuricemia group and a normal serum uric acid group (control group) according to their serum uric acid levels. Then, the participants were further divided into a non-GIL group or a GIL group based on the patient’s renal biopsy results. The two groups’ clinical and pathological data and meaningful indicators for differences were analyzed by binary logistic regression analysis. Additionally, the serum uric acid level prediction value on GIL was investigated using receiver operating characteristic (ROC) curves. Compared with the control group, the hyperuricemia group exhibited high serum uric acid, the prevalence of GIL, serum albumin, the prevalence of hypertension, and low-density lipoprotein cholesterol (LDL) levels (P

IntroductionNonketotic hyperglycinemia (NKH) is a rare, life-threatening genetic disorder. The patients usually show heterogeneous and nonspecific symptoms, resulting in diagnosis challenges using conventional approaches. Here, the clinical presentation and genetic features of 20 Chinese patients were examined and reported in order to clarify the natural history and prognosis of NKH in China.MethodsThe Human Gene Mutation Database and literature regarding NKH in China were reviewed. Age of onset, clinical characteristics, genetic analysis, cranial magnetic resonance imaging (MRI) and electroencephalography (EEG) examinations, and outcome of the patients were analyzed. Natural history experiences and follow-up assays for five patients who were followed in our center were described.ResultsAmong all 20 NKH patients, 17 (85%) had the neonatal type and 3 (15%) had the infantile type, no late-onset cases were detected. Patients showed up for admission with a history of seizures (15/20), lethargy (14/20), hypotonia (11/20), apnea (9/20), and feeble sobbing (4/20). Brain MRI findings included abnormal signals in the internal capsule, cerebellum, or brainstem (6/14), dysplasia of the corpus callosum (5/14), and white matter abnormalities (3/14). EEG evaluations showed anomalies such as burst suppression (4/8) and hypsarrhythmia and/or epileptic activity (6/8). Median values of cerebrospinal fluid (CSF) glycine levels, plasma glycine levels and CSF/plasma glycine ratios were135.2 (range, 6.3–546.3) μmol/L, 998.2 (range,75–3,084) μmol/L, 0.16 (range, 0.03–0.60) respectively. Genetic analyses revealed four new variations and GLDC, AMT gene abnormalities in 13 (65%), 7 (35%) case, respectively. Prognosis information was available for 18 cases: nine patients died, eight in the neonatal period. Among the nine survivors, varying developmental disorders were observed.DiscussionDifferent disease processes and outcomes were found in Chinese NKH patients, according to this study. The initial clinical presentations, CSF glycine levels and CSF to plasma glycine ratios do not reliably predict prognosis, while MRI and EEG abnormalities may indicate a poor outlook. NKH diagnosis should be considered for neonates presenting specific symptoms. The present survey provides clinical data that support the development of a standardized protocol for diagnosing and treating NKH in China.

H-type finned tube heat exchangers have been widely used in boilers and waste heat recovery devices due to their advantages of wear resistance and anti-fouling. In order to improve the energy-saving effect, the flow and heat transfer characteristics of H-type finned tube heat exchangers with different tube bundle arrangements were studied. It was found that, at the same Re number, the column staggered arrangement can compensate for the limited heat transfer performance of the in-line arrangement and reduce the high pressure drop associated with the row staggered arrangement. Honeycomb arrangement was proposed based on the column staggered arrangement. Then, the effects of Re and tube pitches thermal-hydraulic performance of tube bundles with in-line and honeycomb arrangements were examined. The critical tube pitch or velocity at which the honeycomb tube bundle achieves the same thermal performance as the in-line tube bundle are determined. The results provide valuable insights for the practical application of flue gas heat exchangers with honeycomb arrangement.

Introduction: Epstein-Barr virus-positive (EBV+) inflammatory follicular dendritic cell (FDC) sarcoma is a rare neoplasm characterized by spindle-shaped follicular dendritic cells, marked lymphoplasmacytic infiltration, and a consistent link to EBV. While it typically affects the liver and spleen, it is exceptionally rare in the digestive tract. We present a special case of EBV + inflammatory FDC sarcoma arising in the colon with clonal immunoglobulin (IG) gene rearrangement. Case presentation: A 70-year-old man presented with a one-month history of abdominal distension. Colonoscopy revealed a pedunculated polyp in the ascending colon, which was subsequently removed via endoscopic polypectomy. Histological examination of the colonic polyp demonstrated a pronounced lymphoplasmacytic infiltrate with scattered EBV + neoplastic cells, as evidenced by EBV-encoded small RNA in situ hybridization (EBER ISH). The neoplastic cells were positive for FDC-specific markers, including CD21, CD35, and CD23. Additionally, the tumor exhibited clonal rearrangement of the immunoglobulin heavy chain (IGH) gene. The diagnosis was confirmed as EBV + inflammatory follicular dendritic cell sarcoma. Conclusions: We described an exceptional case of EBV + inflammatory FDC sarcoma presenting as a colonic polyp, featuring a clonal IGH gene rearrangement not previously documented in this colonic tumor type. Heightened awareness of this rare neoplasm within the gastrointestinal tract is essential for both accurate diagnosis and effective patient management.

IntroductionThe macrobenthos are crucial for the stability of estuarine ecosystems due to their burrowing behavior in the sediment and their uptake of nutrients from plants. These activities lead to significant alterations in both the morphological and biogeochemical processes within the region.MethodsHowever, there is limited investigation into carbon cycling processes specifically related to crab bioturbation. Additionally, few studies have examined enzymatic activities and carbon fractions in sediments from crab burrow walls at different crab growth stages. This study aims to explore the impact of both plant invasiveness and crab bioturbation on carbon storage.ResultsOur findings suggest that plant invasion leads to higher organic accumulation due to the reduction of recalcitrant organic carbon (ROC) (decreased by 11.6% in invasive and 62.6% in native site from April to December), faster photosynthetic rates (25.8 μmol/m2 s in invasive and 10.7 μmol/m2 s in native site), and an increased presence of arbuscular mycorrhizal fungi (AMF) in the soil over time. However, the increase of easy oxidized carbon (EOC) may lead to less carbon storage in soil (increase by 67.7% in invasive and 48.8% in native site from April to December). In addition to invasiveness, the bioturbation activities of macrobenthos also affect carbon storage. Sediments from crab burrows exhibit higher EOC content (33.6% more than the bulk soil) and higher levels of carbon cycling-related enzymes, including S-ACT, S-β-GC, and S-ACP activities (24.2%, 8.99%, and 135.6% higher than the bulk soil, respectively).DiscussionThese changes contribute to reduced carbon accumulation in the soil. Therefore, crab bioturbation is a more significant factor affecting carbon sink capacity than plant invasion.

Abstract Monolayer molybdenum disulfide (MoS2), an emergent two-dimensional (2D) semiconductor, holds great promise for transcending the fundamental limits of silicon electronics and continue the downscaling of field-effect transistors. To realize its full potential and high-end applications, controlled synthesis of wafer-scale monolayer MoS2 single crystals on general commercial substrates is highly desired yet challenging. Here, we demonstrate the successful epitaxial growth of 2-inch single-crystal MoS2 monolayers on industry-compatible substrates of c-plane sapphire by engineering the formation of a specific interfacial reconstructed layer through the S/MoO3 precursor ratio control. The unidirectional alignment and seamless stitching of MoS2 domains across the entire wafer are demonstrated through cross-dimensional characterizations ranging from atomic- to centimeter-scale. The epitaxial monolayer MoS2 single crystal shows good wafer-scale uniformity and state-of-the-art quality, as evidenced from the ~100% phonon circular dichroism, exciton valley polarization of ~70%, room-temperature mobility of ~140 cm2v−1s−1, and on/off ratio of ~109. Our work provides a simple strategy to produce wafer-scale single-crystal 2D semiconductors on commercial insulator substrates, paving the way towards the further extension of Moore’s law and industrial applications of 2D electronic circuits.

Abstract Stacking order plays a crucial role in determining the crystal symmetry and has significant impacts on electronic, optical, magnetic, and topological properties. Electron-phonon coupling, which is central to a wide range of intriguing quantum phenomena, is expected to be intricately connected with stacking order. Understanding the stacking order-dependent electron-phonon coupling is essential for understanding peculiar physical phenomena associated with electron-phonon coupling, such as superconductivity and charge density waves. In this study, we investigate the effect of stacking order on electron-infrared phonon coupling in graphene trilayers. By using gate-tunable Raman spectroscopy and excitation frequency-dependent near-field infrared nanoscopy, we show that rhombohedral ABC-stacked trilayer graphene has a significant electron-infrared phonon coupling strength. Our findings provide novel insights into the superconductivity and other fundamental physical properties of rhombohedral ABC-stacked trilayer graphene, and can enable nondestructive and high-throughput imaging of trilayer graphene stacking order using Raman scattering.

Abstract Lung cancer is the second most common and the deadliest type of cancer worldwide. Clinically, non‐small cell lung cancer (NSCLC) is the most common pathological type of lung cancer; approximately one‐third of affected patients have locally advanced NSCLC (LA‐NSCLC, stage III NSCLC) at diagnosis. Because of its heterogeneity, LA‐NSCLC often requires multidisciplinary assessment. Moreover, the prognosis of affected patients is much below satisfaction, and the efficacy of traditional therapeutic strategies has reached a plateau. With the emergence of targeted therapies and immunotherapies, as well as the continuous development of novel radiotherapies, we have entered an era of novel treatment paradigm for LA‐NSCLC. Here, we reviewed the landscape of relevant therapeutic modalities, including adjuvant, neoadjuvant, and perioperative targeted and immune strategies in patients with resectable LA‐NSCLC with/without oncogenic alterations; as well as novel combinations of chemoradiation and immunotherapy/targeted therapy in unresectable LA‐NSCLC. We addressed the unresolved challenges that remain in the field, and examined future directions to optimize clinical management and increase the cure rate of LA‐NSCLC.

Dwarfing rootstocks enhance planting density, lower tree height, and reduce both labor in peach production. Cerasus humilis is distinguished by its dwarf stature, rapid growth, and robust fruiting capabilities, presenting substantial potential for further development. In this study, Ruipan 4 was used as the scion and grafted onto Amygdalus persica and Cerasus humilis, respectively. The results indicate that compared to grafting combination R/M (Ruipan 4/Amygdalus persica), grafting combination R/O (Ruipan 4/Cerasus humilis) plants show a significant reduction in height and a significant increase in flower buds. RNA-seq indicates that genes related to gibberellin (GA) and auxin metabolism are involved in the dwarfing process of scions mediated by C. humilis. The expression levels of the GA metabolism-related gene PpGA2ox7 significantly increased in R/O and are strongly correlated with plant height, branch length, and internode length. Furthermore, GA levels were significantly reduced in R/O. The transcription factor PpGATA21 was identified through yeast one-hybrid screening of the PpGA2ox7 promoter. Yeast one-hybrid (Y1H) and dual-luciferase reporter (DLR) demonstrate that PpGATA21 can bind to the promoter of PpGA2ox7 and activate its expression. Overall, PpGATA21 activates the expression of the GA-related gene PpGA2ox7, resulting in reduced GA levels and consequent dwarfing of plants mediated by C. humilis. This study provides new insights into the mechanisms of C. humilis and offers a scientific foundation for the dwarfing and high-density cultivation of peach trees.

The conversion of tidal wetlands to open water has become a major concern for coastal managers worldwide. Collecting spatial information regarding the lost tidal wetlands resulting from open-water conversion and the degraded tidal wetlands that are exhibiting a significant transition towards open water is the prerequisite for employing conservation and restoration efforts. Previous studies have focused on the former information while often neglecting the latter. This will hamper coastal managers to make comprehensive decisions. In this study, tidal wetlands along the mainland coast of China are taken as a case. Using a linear regression model, we first verify that the time series water percent maps can capture the changes in inundation of tidal wetlands at the local scale, and then employ this dataset and method to identify the portions within the current tidal wetlands (2020) that are exhibiting a significant transition toward open-water at the national scale. Furthermore, we optimize the spatial information of the lost tidal wetlands resulting from open-water conversion on the mainland coast of China from 1999 to 2019 based on a global intertidal change database. The results suggest that a total of 5.3 × 104 ha of tidal wetlands were converted into open-water on the mainland coast of China between 1999 and 2019, with over 57% of this occurring in Jiangsu Province and Shandong Province. Nearly 12% of China’s current tidal wetlands, equivalent to 10.1 × 104 ha, are undergoing a significant transition toward open water. The area proportion of these degraded wetlands in the provinces north of Shanghai is generally higher than that in the provinces south of Shanghai, except for Hainan Province. The four-quadrant model is utilized to provide conservation and restoration recommendations for different coastal segments based on the comprehensive spatial information on the open-water conversion of tidal wetlands. The datasets and methods used in this study provide novel insights for determining open-water conversion of tidal wetlands. Our findings have the potential to assist coastal managers in optimizing the spatial patterns of the national restoration projects along the mainland coast of China.

Abstract In the process of contemporary agricultural production, the application of intelligent connection and automatic navigation technology of modern agricultural machinery is increasingly common. The application of visual navigation technology in the field of intelligent connection of agricultural machines can provide accurate and reliable positioning signals for agricultural machines so as to carry out intelligent and automatic agricultural machinery operations. In order to realise precision agricultural operation and intelligent navigation, a network of combining decision‐making by using visual navigation recognition and image processing is proposed. The system design mainly includes two parts: visual navigation system and control network. Agricultural machinery uses monocular vision image acquisition to collect farmland image. The computer analyzes the image, extracts the navigation centreline, obtains the navigation path information, and completes the identification and positioning of the navigation path. The simulation process verifies that the designed image navigation precision agricultural intelligent connection network can provide efficient, precise, and intelligent control of agricultural machinery.

Abstract Monolayer molybdenum disulfide (ML-MoS2) is an emergent two-dimensional (2D) semiconductor holding potential for flexible integrated circuits (ICs). The most important demands for the application of such ML-MoS2 ICs are low power consumption and high performance. However, these are currently challenging to satisfy due to limitations in the material quality and device fabrication technology. In this work, we develop an ultra-thin high-κ dielectric/metal gate fabrication technique for the realization of thin film transistors based on high-quality wafer scale ML-MoS2 on both rigid and flexible substrates. The rigid devices can be operated in the deep-subthreshold regime with low power consumption and show negligible hysteresis, sharp subthreshold slope, high current density, and ultra-low leakage currents. Moreover, we realize fully functional large-scale flexible ICs operating at voltages below 1 V. Our process could represent a key step towards using energy-efficient flexible ML-MoS2 ICs in portable, wearable, and implantable electronics.

Based on air-, water-, and ground-source heat pump systems, a novel type of heat pump system, named the heat-source tower heat pump system (HSTHPS), has recently been developed in the southern area of China. The HSTHPS overcomes the evaporator frosting problems of the air-source heat pump system (ASHPS) when the ambient temperature is lower, and it avoids the geological condition constraints of the water- and ground-source heat pump systems. However, studies on the HSTHPS are insufficient, thereby limiting its development and applications. Thus, the present review provides a detailed literature review on the advancements of HSTHPSs in China, including the HSTHPS operation principle, heat-source tower (HST) structure, heat and mass transfer characteristics, HSTHPS performance, antifreeze solution use, and antifreeze solution regeneration. Studies on the heat and mass transfer characteristics of HSTs are sufficient for guiding the application. Regarding open systems, the solution drifting to the air needs to resolved, and future studies need to focus on structure optimization for heat exchangers in closed systems. Moreover, advanced defrosting technology should be applied to closed-type HSTs, and a suitable operation strategy for HSTHPSs should be developed. Future priorities should involve integrating HSTHPSs with additional renewable energy in order to achieve continuous, stable, and efficient heating in winter based on the characteristics of local climate and renewable energy.

Anthracnose is extremely detrimental to walnut production, because it seriously affects its yield. Therefore, this study aimed to identify anthracnose resistance genes in walnuts, to lay the foundation for cultivating novel anthracnose-resistant walnut varieties. In this study, the fruits of walnut varieties “Qinyou 1” and “Qinyou 2”, exhibiting relatively weak resistance to anthracnose, were used for transcriptome sequencing and identifying differentially expressed genes (DEGs). Thereafter, we used a quantitative real-time polymerase chain reaction to verify the reliability of the transcriptome data using the walnut varieties Qinyou 1, Qinyou 2, Qinyou 3, Liaohe 1, and Diamond 1. We identified 6326 DEGs post-infection in Qinyou 1, of which 3065 were upregulated and 3261 were downregulated. We also found 2055 DEGs (969 upregulated and 1086 downregulated genes) in the two varieties, after 6 days of anthracnose infection. Based on GO and KEGG enrichment analyses of the transcriptome data, we noted that the DEGs were primarily involved in metabolic processes, cell composition, cell structure, catalytic activity, and binding activity. Furthermore, KEGG functional enrichment analysis showed that the amino acid biosynthesis pathway and plant–pathogen interaction may be activated under anthracnose infection. We also noted that the expression levels of anthracnose resistance genes in different walnut varieties were significantly different. Thus, the findings of this study provide important genetic resources and molecular markers for the cultivation of novel anthracnose-resistant walnut varieties.

Coastlines with extensive estuaries and broad tidal flats are acutely vulnerable to coastal development. The tidal wetlands of the Yellow Sea are globally important for waterbirds, yet river mouths have disproportionately been developed as industrial ports, fishing ports, or have become abandoned fishing ports, with the type of management strategies depending on biophysical attributes and regional economic drivers. However, river mouths also support extensive upper tidal flat ecosystems, in contrast to many open coastal regions of the Yellow Sea, where reclamation has excised many of the upper tidal flats and dramatically reduced the time that tidal flats are available for foraging and roosting waterbirds each day. However, the extent to which waterbirds disproportionately occurs in river mouths compared to the open coast in the region remains unclear. We used a paired survey design to quantify the waterbird communities and habitat attributes (i.e., areas of upper tidal flats, Spartina alterniflora, and human activity) of 15 river mouths and 15 otherwise similar adjacent open coasts areas along the Yellow Sea coast. Waterbird species richness and abundance were higher in river mouths than open coasts. Among river mouths, the most species rich waterbird communities occurred in fishing ports and the most species poor in industrial ports. Notably, upper tidal flats were absent in many of the open coast regions, which had been subject to reclamation. Our results suggest that river mouths, especially those river mouths currently used as fishing ports, are probably of crucial importance for waterbird conservation on the Jiangsu coast due to their larger areas of upper tidal flats. Our work highlights the need to ensure that the tidal flats in river mouth systems are effectively protected to promote the completion of the annual cycle of migratory waterbirds.

To achieve the Paris Agreement, China pledged to become “Carbon Neutral” by the 2060s. In addition to massive decarbonization, this would require significant changes in ecosystems toward negative CO2 emissions. The ability of coastal blue carbon ecosystems (BCEs), including mangrove, salt marsh, and seagrass meadows, to sequester large amounts of CO2 makes their conservation and restoration an important “nature-based solution (NbS)” for climate adaptation and mitigation. In this review, we examine how BCEs in China can contribute to climate mitigation. On the national scale, the BCEs in China store up to 118 Tg C across a total area of 1,440,377 ha, including over 75% as unvegetated tidal flats. The annual sedimental C burial of these BCEs reaches up to 2.06 Tg C year−1, of which most occurs in salt marshes and tidal flats. The lateral C flux of mangroves and salt marshes contributes to 1.17 Tg C year−1 along the Chinese coastline. Conservation and restoration of BCEs benefit climate change mitigation and provide other ecological services with a value of $32,000 ha−1 year−1. The potential practices and technologies that can be implemented in China to improve BCE C sequestration, including their constraints and feasibility, are also outlined. Future directions are suggested to improve blue carbon estimates on aerial extent, carbon stocks, sequestration, and mitigation potential. Restoring and preserving BCEs would be a cost-effective step to achieve Carbon Neutral by 2060 in China despite various barriers that should be removed. Public summary: • Protecting and restoring coastal ecosystems such as mangroves, salt marshes, tidal flats, and seagrass meadows can be a key strategy for China to achieve its goal of carbon neutrality by 2060. • Coastal ecosystems in China alone have stored large amounts of carbon, approximately 118 Tg C. • In addition to helping fight climate change, protecting these ecosystems also provides other cost-effective benefits, including storm protection, shoreline stabilization, water conservation, purification, high biodiversity, and productivity.

Growth hormone deficiency (GHD) has become a serious healthcare burden, and presents a huge impact on the physical and mental health of patients. Here, we developed an actively separated microneedle patch (PAA/NaHCO3-Silk MN) based on silk protein for sustained release of recombinant human growth hormone (rhGH). Silk protein, as a friendly carrier material for proteins, could be constructed in mild full-water conditions and ensure the activity of rhGH. After manually pressing PAA/NaHCO3-Silk MN patch to skin for 1 min, active separation is achieved by absorbing the interstitial fluid (ISF) to trigger HCO3‒ in the active backing layer to produce carbon dioxide gas (CO2). In rats, the MN patch could maintain the sustained release of rhGH for more than 7 days, and produce similar effects as daily subcutaneous (S.C.) injections of rhGH in promoting height and weight with well tolerated. Moreover, the PAA/NaHCO3-Silk MN patch with the potential of painless self-administration, does not require cold chain transportation and storage possess great economic benefits. Overall, the PAA/NaHCO3-Silk MN patch can significantly improve patient compliance and increase the availability of drugs, meet current unmet clinical needs, improve clinical treatment effects of GHD patients.

Abstract Latexin (LXN) plays an important role in tumorigenesis and inflammatory response and as a tumor suppressor in many tumors. However, whether LXN regulates tumorigenesis through immune regulation remains uncertain. Here, we demonstrate that LXN deficiency increases hematopoietic stem cells, as well as affects the proportion of immune cells in the peripheral system. Animal studies show that mice loss of LXN promotes tumor growth in subcutaneous tumor model and AOM/DSS-induced colorectal cancer model. We found that loss of LXN promotes macrophage M2 polarization and PD-L2 expression in macrophage, thus, inhibits the function of T cells. Adoptive transfer of wild-type macrophage rescues the function of T cells in LXN-deficient mice. LXN deficiency in hematopoietic lineage exacerbates colorectal carcinogenesis, and targeted inhibition of PD-L2 ameliorates cancer growth in LXN-deficient mice. Mechanistically, we demonstrate that LXN inhibits STAT3 transcriptional activity by targeting inhibition of JAK1 in macrophages. LXN deficiency enhances PD-L2 expression rather than PD-L1 in macrophages, which lead to inhibition of T cells in tumor microenvironment. Collectively, we define a critical role of LXN/JAK1/STAT3 signal in macrophage and highlights the potential role of LXN in tumor immune-escape by regulating macrophage polarization, as well as the expression of immune checkpoint PD-L2.

Vitiligo is a common depigmentation disease. Childhood vitiligo exhibits some characteristics in epidemiology, clinical manifestations, comorbidities, etc. In addition, considering the unique features of children's growth and development stages, the therapeutic approaches for pediatric vitiligo are different from those for adults. Although traditional therapy is still the main treatment for childhood vitiligo, glucocorticoids, calcipotriol and other conventional methods have limited efficacy. Hence, new therapies, including Janus kinase inhibitor, afamelanotide and prostaglandin analogues, are introduced in the treatment of vitiligo and are expected to be applied to children. Therefore, this article summarizes the characteristics, domestic and foreign guidelines, clinical trials and the latest research progress in the treatment of childhood vitiligo.

Saltmarshes are valued as key buffering ecosystems against global climate change and sea level rise. However, the knowledge deficit regarding links between colonization of saltmarsh fringes by plants and mud cracking in the lateral dimension considerably limits our understanding of marsh resilience. Here, the role of mud cracks in colonization by saltmarsh plants was investigated. A combination of field experiments, remote sensing, and experimental results revealed that: (1) potential mud cracking zones were formed at the seaward edge of saltmarshes under the influence of tide-induced wetting–drying cycles, where mud cracks were extensively distributed and colonized by new seedlings. (2) The seedling density in the mud cracks was higher than that in the patches, and seedlings in the mud cracks sprouted earlier than those in the patches. The results implied that mud cracking enhanced colonization by saltmarsh plants, rather than being a water stressor. (3) The two main ecological functions of mud cracks in saltmarsh colonization were acting as “seed traps” and “seedling growth promoters.” (4) Mud cracking could be a key factor influencing saltmarsh resilience, especially by promoting the colonization and dispersal of saltmarsh plants. Rapid colonization of potential zones with mud cracks could occur as soon as seeds are available. Our results could facilitate the development of appropriate saltmarsh rehabilitation strategies.

With the capacity to reduce wave energy and trap sediment, Scirpus mariqueter has become an important native species of annual grass for ecology restoration at the Yangtze Estuary in eastern China. Due to seasonal variances of biophysical characteristics, S. mariqueter usually bends and breaks in winter, resulting in flattened stems that may reduce its wave attenuation capacity. To investigate the effects of vegetation flattening on wave attenuation, a set of flume experiments were conducted for flattened and standing vegetation under different wave conditions. The model vegetation was designed to represent the wilted S. mariqueter collected in winter with dynamic similarity. Results showed that the wave damping coefficient for flattened vegetation (βF) was 33.6%-72.4% of that for standing vegetation (βS) with the same vegetation length. Both βF and βS increased with wave height but decreased with water depth. A wave attenuation indicator (WAI) was defined to generate empirical formulas for βS and βF as well as their ratio βF/βS. The empirical formulas were then applied to modify the existing standing vegetation-based wave attenuation model for flattened vegetation and performed successfully. Understanding the wave attenuation characteristics of flattened vegetation is essential for the management of ecological restoration and coastal protection.

Objective: Wiedemann-Steiner syndrome (WSS) is a rare autosomal dominant disorder caused by deleterious heterozygous variants of the KMT2A gene. This study aims to describe the phenotypic and genotypic features of Chinese WSS patients, and assess therapeutic effects of recombinant human growth hormone (rhGH).Methods: Eleven Chinese children with WSS were enrolled in our cohort. Their clinical, imaging, biochemical and molecular findings were analyzed retrospectively. Moreover, the phenotypic features of 41 previously reported Chinese WSS patients were reviewed and included in our analysis.Results: In our cohort, the 11 WSS patients presented with classic clinical manifestations, but with different frequencies. The most common clinical features were short stature (90.9%) and developmental delay (90.9%), followed by intellectual disability (72.7%). The most frequent imaging features were patent ductus arteriosus (57.1%) and patent foramen ovale (42.9%) in cardiovascular system, and abnormal corpus callosum (50.0%) in the brain. In the set comprising 52 Chinese WSS patients, the most common clinical and imaging manifestations were developmental delay (84.6%), intellectual disability (84.6%), short stature (80.8%) and delayed bone age (68.0%), respectively. Eleven different variants, including three known and eight novel variants, of the KMT2A gene were identified in our 11 WSS patients without a hotspot variant. Two patients were treated with rhGH and yielded satisfactory height gains, but one developed acceleration of bone age.Conclusion: Our study adds 11 new patients with WSS, reveals different clinical characteristics in Chinese WSS patients, and extends the mutational spectrum of the KMT2A gene. Our study also shares the therapeutic effects of rhGH in two WSS patients without GH deficiency.

Abstract Background Pathogenic mutations in the PHKG2 are associated with a very rare disease—glycogen storage disease IXc (GSD-IXc)—and are characterized by severe liver disease. Case presentation Here, we report a patient with jaundice, hypoglycaemia, growth retardation, progressive increase in liver transaminase and prominent hepatomegaly from the neonatal period. Genetic testing revealed two novel, previously unreported PHKG2 mutations (F233S and R320DfsX5). Functional experiments indicated that both F223S and R320DfsX5 lead to a decrease in key phosphorylase b kinase enzyme activity. With raw cornstarch therapy, hypoglycaemia and lactic acidosis were ameliorated and serum aminotransferases decreased. Conclusion These findings expand the gene spectrum and contribute to the interpretation of clinical presentations of these two novel PHKG2 mutations.

Abstract Background To investigate hypothalamic-pituitary-thyroid function in children of different ages, nutritional phases, and genotypes that were diagnosed with Prader-Willi syndrome (PWS), as well as the effects of recombinant human growth hormone (rhGH) treatment on thyroid hormones in PWS patients. Methods One hundred and thirty PWS patients (87 boys and 43 girls) aged from newborn to 15 years (y) (median 1.25 y, mean, SD: 2.95 ± 3.45 y), were surveyed in this study. Serum thyroid hormone levels were examined at least once per3-6 months during the 2 years follow-up study. Central hypothyroidism (C-HT) was identified as low/normal thyroid-stimulating hormone (TSH) and low free thyroxine 4 (FT4). Results All study participants had normal neonatal TSH screening test results. The prevalence of C-HT is 36.2% (47/130). No C-HT cases were diagnosed in PWS either below 1 month (m) or above 12 y. The prevalence of C-TH would be increased with age before 3 y until reaching the peak, followed by a gradual decline over the years. The prevalence of C-HT varies significantly at different ages (Pearson's χ2 = 19.915; p

Abstract The striking realism of the life-sized ceramic terracotta warriors has been attracting the interest of the public and archaeologists since they were discovered from the mausoleum complex of the first Chinese Emperor Qin Shihuang in the 1970s. It is still debated whether the life-size models were based on individual people or were just crafted from the standardized models. This research examined the facial features of the terracotta warriors in a quantitative and contactless way with the support of the High-precision 3D point cloud modelling technology and the anthropometric method. The similarities and dissimilarities were analyzed among the facial features of terracotta warriors and 29 modern Chinese ethnic groups using mathematical statistics methods such as MDS, ANOVA, ranking analysis and cluster analysis. The results reveal that the features of the terracotta warriors highly resemble those of contemporary Chinese people and indicate that terracotta warriors were crafted from real portraits and intended to constitute a real army to protect the Emperor Qin Shihuang in the afterlife.

Abstract Background Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common human genetic abnormalities, with a high prevalence in Guangdong, China. The purpose of this study was to explore the characteristics of newly diagnosed type 1 diabetes (T1D) patients with G6PD deficiency in a cohort of Chinese children and to investigate the relationship between the diabetic ketoacidosis (DKA) and hemolysis due to G6PD deficiency in these patients. Methods A total of 503 newly diagnosed T1D children aged 6 months–18 years were collected and their G6PD enzyme activity were measured. Fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), and G6PD gene were analysed. The pH, HCO3, and plasma osmotic pressure between DKA patients with and without hemolysis at the presentation were compared. Results In the present study, G6PD deficiency accounted for 5.3% of newly diagnosed T1D children. There were no significant differences in FPG/HbA1c and HbA1c levels between T1D children alone and T1D children with G6PD deficiency. Hemolysis appeared in five of the twenty-two DKA patients with G6PD deficiency. Two patients had fever at onset and were given ibuprofen and cefazolin. The other three patients did not have infection or ingestion of hemolytic drugs. There were no significant difference in pH, HCO3, and osmotic pressure between the children with DKA with and without hemolysis at the presentation. The hemolysis occurred between 2 and 7 days after admission and the hyperglycaemia had been corrected by the time hemolysis occurs. Four G6PD gene mutations were found in the diabetes with G6PD deficiency patients: c.1376G > T, c.1388G > A, c.95A > G, and c.871G > A, all of which were genes with high frequency of G6PD deficiency in Guangdong Province. No correlation between genotype and hemolysis was found. Conclusion In the present study, we found the frequency of G6PD deficiency among newly diagnosed T1D children was similar to that of the general population. However, DKA children with G6PD deficiency are prone to occur hemolytic anemia, and these hemolysis usually occurs when DKA is corrected and blood glucose is in homeostatic state, which is easy to be ignored. To reduce the risk of this complication, especially in areas with high incidence of G6PD deficiency, screening for G6PD activity in people with newly diagnosed diabetes should be considered.

Abstract Background Sitosterolemia is a lipid disorder characterized by the accumulation of phytosterols in plasma and organs, caused by mutations in the ABCG5 and/or ABCG8 genes. The disease is frequently misdiagnosed and mistreated as familial hypercholesterolemia (FH). To gain a better understanding of the disease, the current status of diagnosis and treatment of Chinese patients with sitosterolemia was reviewed and summarized. Method Literature search was performed. The clinical features and molecular characteristics of Chinese patients with sitosterolemia were analysed. Four children with sitosterolemia and the treatment experience were described. Results Fifty-five patients with sitosterolemia have been reported in China. These patients were aged from 3 months to 67 years at diagnosis, and the median was 8 years of age. Several complications, such as xanthomas in 47 patients (85%), thrombocytopenia in 17 patients (31%), anemia in 14 patients (25%), and cardiovascular damage in 12 patients (22%), were observed. Thirty-nine patients (71%) exhibited mutations in the ABCG5 gene, 15 patients (27%) showed mutations in ABCG8, and variations in both genes occurred in one patient (2%). A patient with two clinically rare diseases, namely, sitosterolemia and glycogen storage disease type VI (GSD VI)), is reported here for the first time. The four reported patients were treated with low cholesterol and phytosterol-limited diet alone or combined with cholestyramine. Even though decreases were observed for total plasma cholesterol (TC) and low-density-lipoprotein cholesterol (LDL-C), and these levels were as low as normal in some patients, the levels of plant sterols remained above the normal range. However, TC, LDL-C and plant sterol levels remained at high levels in patients treated with a control diet control only. Conclusions The analysis reveals that different from Caucasians carrying mainly variations in ABCG8, most Chinese patients have mutations in the ABCG5 gene, and Arg446Ter, Gln251Ter, anArg389His might be hot-spot mutations in Chinese patients. The current survey provides clinical data to enable the development of a standardized protocol for the diagnosis and treatment of sitosterolemia in China.

Governments and non-governmental organizations have widely recognized tidal wetland restoration as a sustainable instrument to lessen the threat of climate change, which is reflected by the expansion of the spatial scale of coastal restoration projects. However, approaches to large-scale spatial planning of tidal wetland restoration remain sparse. Previous studies on site selection for restoration planning have focused on the potential supply of ecosystem services (ES) or restoration feasibility with less emphasis on the mitigation of the status of regional ES supply and demand mismatches. We developed a five-step workflow based on systematic conservation planning to identify priority areas for tidal wetland restoration and applied it to the coastal reclaimed areas of Shanghai, China. With this workflow, we analyzed the changes in spatial distribution and the potential ecosystem services supply and restoration costs of priority areas between the two different scenarios of ES demand ignored and ES demand considered. Results showed that the potential restorable areas only accounted for 31.4% (425.2 km²) of the original reclaimed area because of other land use demands (e.g., permanent basic farmland conservation). We extracted 50% of the potential restorable areas as priority areas based on Aichi Target 15. Compared with the ES demand-ignored scenario, the ES demand scenario resulted in a substantial increase in the priority areas of Baoshan District (~177%) and Pudong New Area (~15%) and a small decrease in Chongming District (~4%). No significant change in the potential ES supply for all priority areas was observed between the two scenarios. However, the total restoration cost of the ES demand scenario is 10% higher than that of the ES demand-ignored scenario. Our study highlights the importance of considering the status of regional ES supply and demand (mis)matches in large-scale spatial planning for tidal wetland restoration.

Peach trees play an essential role as an economic crop in China. However, the increasing cost of labor has led to a decline in the benefits of peach cultivation. The use of dwarfing rootstock technology can increase planting density, reduce tree height, decrease labor requirements, and reduce production costs. The Cerasus humilis (Bge). Sok. is a promising dwarfing rootstock for peaches owing to its small tree size, abundant resources, strong resistance, and adaptability. In this study, we investigated the effect of Cerasus humilis rootstocks on peach growth and development, and related gene expression. We used Ruipan 4/Cerasus humilis and Ruipan 4/Amygdalus persica L. as experimental materials to measure the growth and fruiting characteristics of two-year-old Cerasus humilis rootstocks. In addition, we used bioinformatic methods to explore the effect of Cerasus humilis rootstock on peach growth gene expression. Our results showed that Cerasus humilis rootstocks can dwarf peach trees, reduce branches, increase pollen count and stigma receptivity, shorten spore development, and promote protein accumulation in the late stage of fruit maturity. The Cerasus humilis rootstock reduced the growth hormone content in peach trees while upregulating the expression of growth-related PpYucca5 and PpYucca2 genes. PpYucca6 expression was downregulated in the early stage of shoot growth and upregulated in the middle stage. By reducing the content of growth hormones, peach trees can be dwarfed, but their impact on fruit quality is minimal. These results indicate that Cerasus humilis is a suitable peach dwarfing rootstock and can provide a theoretical reference for the future breeding of peach dwarfing rootstocks.

Sichuan—Tibet Railway is the national important infrastructure construction projects, and ensuring the smooth construction and the safe post operation of the railway is very important. The large-scale landslides with extensive development and serious damage along the railway have become the key control nodes of the railway and even the whole line, which is related to the success of the project construction. This paper takes large landslides along the railway (including giant landslides) as the main research object. Based on the field investigation and remote sensing interpretation of the large-scale landslides, the contributing weights model is used to assess the large-scale landslides hazard along the railway area in the ArcGIS platform and the Natural Breaks method is used to partition and statistically analyze the hazard assessment results. The results show that there are 147 large and extra-large landslides along the Sichuan—Tibet Railway, including 106 large landslides and 41 large landslides, mainly distributed in the zone of Baiyu to Jiangda, Changdu to Basu, Lang County to Jiacha. The areas along the railway in the three-level (high, moderate and low) dangerous areas are 35918.5 km2, 95484.3 km2 and 12039.7 km2 respectively, and the distribution density of large-scale landslides in the high hazard area is 0.00199/km−2, which is approximately two times of the moderate and the low hazard area. The high hazard area is mainly concentrated in the zone of Bangda to Basu, Guxiang to Layue, and Baiyu to Jiangda. It can be seen that the hazard scale of the large landslide along the Sichuan-Tibet Railway calculated by the contributing weights model is consistent with the landslide distribution density of the field survey. Relevant research results can provide scientific reference and basis for the construction of Sichuan—Tibet Railway project.

Tumor protein 53 (TP53) mutation predicts an unfavorable prognosis in diffuse large B-cell lymphoma (DLBCL), but the molecular basis for this association remains unclear. In several malignancies, the cytidine deaminase apolipoprotein B mRNA editing enzyme catalytic subunit 3B (APOBEC3B) has been reported to be associated with the TP53 G/C-to-A/T mutation. Here, we show that the frequency of this mutation was significantly higher in relapsed/refractory (R/R) than in non-R/R DLBCL, which was positively associated with the APOBEC3B expression level. APOBEC3B overexpression induced the TP53 G/C-to-A/T mutation in vitro, resulting in a phenotype similar to that of DLBCL specimens. Additionally, APOBEC3B-induced p53 mutants promoted the growth of DLBCL cells and enhanced drug resistance. These results suggest that APOBEC3B is a critical factor in mutant p53-driven R/R DLBCL and is therefore a potential therapeutic target.

ObjectivesTo reveal the effects of repetitive transcranial magnetic stimulation (rTMS) on the improvement of cognitive function in patients with stress-related depression, and to enrich the neural mechanism(s) underlying rTMS so as to improve cognitive function in patients with stress-related depression.MethodsWe conducted a randomized, double-blind, placebo-controlled study of rTMS in patients with stress-related depression who were 18–40 years of age. Patients were randomly allocated to either a sham or experimental group in a 1:1 ratio. A 10-session rTMS protocol was used with 10-Hz stimulation over the left dorsolateral prefrontal cortex (DLPFC). Clinical assessments (HAMD, HAMA, DASS, MoCA), neuropsychologic (Stroop, WCST), and resting state fMRI and 1H-MRS assessments were executed at two time points—baseline and after the 10th rTMS session.ResultsrTMS relieved the mental symptoms of patients in both groups. The MoCA score of patients in the experimental group increased; the number of correct answers increased significantly in Stroop testing, and the number of errors and omissions decreased significantly; the number of persistent errors decreased significantly; and the time used to complete the test decreased to an even greater extent in the WCST experimental group. The ReHo value in the lingual gyrus of the right hemisphere and the cuneus of the left and right hemispheres in the experimental group decreased after treatment. The DC value in the left and right hemispheric cuneus and postcentral gyrus of the left hemisphere in the experimental group diminished after treatment. The functional connections of these brain regions also changed as the Cho and NAA/Cr of the left DLPFC changed, with alterations related to the improvement in cognitive function. The level of choline (Cho) in the left DLPFC of the experimental group was significantly lower than that of the control group, and the level of N-acetylaspartate/creatine (NAA/Cr) in the left DLPFC of the control group was significantly higher than that of the experimental group. These changes were related to the overall improvement in cognitive function.ConclusionsTen-Hz rTMS over the left DLPFC improved the cognitive function of patients with stress-related depression. The governing mechanism for this phenomenon may be via rTMS effects on multiple visual-related brain regions and their functional connections, and on the somatosensory cortex and its functional connection with visual and auditory cortex, reducing the level of Cho and stabilizing the level of NAA/Cr in the left DLPFC.

Both insect ecdysone receptors and ultraspiracle belong to the nuclear receptor family. They form a nanoscale self-assembling complex with ecdysteroids in cells, transit into the nucleus, bind with genes to initiate transcription, and perform specific biological functions to regulate the molting, metamorphosis, and growth processes of insects. Therefore, this complex is an important target for the development of eco-friendly insecticides. The diamondback moth (Plutella xylostella) is a devastating pest of cruciferous vegetable crops, wreaking havoc worldwide and causing severe economic losses, and this pest has developed resistance to most chemical insecticides. In this study, highly pure EcR and USP functional domains were obtained by constructing a prokaryotic expression system for the diamondback moth EcR and USP functional domain genes, and the differences between EcR and USP binding domain monomers and dimers were analyzed using transmission electron microscopy and zeta potential. Radioisotope experiments further confirmed that the binding affinity of PonA to the EcR/USP dimer was enhanced approximately 20-fold compared with the binding affinity to the PxGST−EcR monomer. The differences between PonA and tebufenozide in binding with EcR/USP were examined. Molecular simulations showed that the hydrogen bonding network formed by Glu307 and Arg382 on the EcR/USP dimer was a key factor in the affinity enhancement. This study provides a rapid and sensitive method for screening ecdysone agonists for ecdysone receptor studies in vitro.

A numerical simulation on the heat transport augmentation and flow drag behavior of spirally corrugated pipes was performed. The simulation was conducted on the basis of the experimental results documented in the published literature. The influence of the thread height and pitch on the hydraulic–thermal performance as well as the mechanism of the convection heat transport development inside the spirally corrugated pipe were explored. It was discovered that the convection heat transport performance elevates in the Reynolds number region of 4000~13,000 as the thread height rises or the Reynolds number enlarges, but it declines when the thread pitch extends. The convection heat transport performance marked by the Nusselt number of the spirally corrugated pipe could reach 2.77 times that of the plain pipe, while the flow resistance coefficients of spirally corrugated pipes are 89~324% above that of the plain pipe. It enlarges with the rise in thread height but declines with the extension of the thread pitch. It also reduces when the Reynolds number enlarges. The factors of overall heat transmission performance for all the spirally corrugated pipes are above 1.00, and they increase in the Reynolds number region of 4000~7000 and then decrease in the Reynolds number region of 7000 to 13,000. The secondary flow at the cross-sections and the vortex between two adjacent corrugated grooves are the basic causes of the promotion of convection heat transport inside the spirally corrugated pipes. The secondary flow near the pipe wall both disrupts the border layer and boosts the radial interfusion of the fluid. In addition, the existence of vortexes makes the secondary flow act on the convection heat transmission continuously and positively in the region close to the pipe wall.

Transaldolase (TALDO) deficiency is a rare autosomal recessive disorder caused by variants in the TALDO1 gene that commonly results in multisystem dysfunction. Herein, we reported compound heterozygous variants in a Chinese prenatal case with TALDO deficiency using whole-exome sequencing (WES) for trios and Sanger sequencing. The heterozygous variants were located on the TALDO1 gene: NM_006755.2:c.574C > T(Chr11:g.763456C > T), a missense variant in exon 5 paternally inherited; NM_006755.2:c.462-2A > G(Chr11:g.763342A > G), a splicing aberration in intron 4 maternally inherited. The qualitative analysis of urinary polyols in neonatal urine indicated that xylitol + arabitol and ribitol in the proband’s urine were significantly increased. These findings expand the variation spectrum of the TALDO1 gene, provide solid evidence for the counseling of the family in regard to future pregnancies, strongly support the application of WES in prenatal diagnosis, and further prove that effective postpartum treatments could improve prognosis.

San-Huang-Yi-Shen capsule (SHYS) has been used in the treatment of diabetic nephropathy (DN) in clinic. However, the mechanisms of SHYS on DN remain unknown. In this study, we used a high-fat diet (HFD) combined with streptozotocin (STZ) injection to establish a DN rat model. Next, we used 16S rRNA sequencing and untargeted metabolomics to study the potential mechanisms of SHYS on DN. Our results showed that SHYS treatment alleviated the body weight loss, hyperglycemia, proteinuria, pathological changes in kidney in DN rats. SHYS could also inhibite the oxidative stress and inflammatory response in kidney. 16S rRNA sequencing analysis showed that SHYS affected the beta diversity of gut microbiota community in DN model rats. SHYX could also decrease the Firmicutes to Bacteroidetes (F to B) ratio in phylum level. In genus level, SHYX treatment affected the relative abundances of Lactobacillus, Ruminococcaceae UCG-005, Allobaculum, Anaerovibrio, Bacteroides and Candidatus_Saccharimonas. Untargeted metabolomics analysis showed that SHYX treatment altered the serum metabolic profile in DN model rats through affecting the levels of guanidineacetic acid, L-kynurenine, prostaglandin F1α, threonine, creatine, acetylcholine and other 21 kind of metabolites. These metabolites are mainly involved in glycerophospholipid metabolism, tryptophan metabolism, alanine, aspartate and glutamate metabolism, arginine biosynthesis, tricarboxylic acid (TCA) cycle, tyrosine metabolism, arginine and proline metabolism, arginine and proline metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, and D-glutamine and D-glutamate metabolism pathways. Spearman correlation analysis showed that Lactobacillus, Candidatus_Saccharimonas, Ruminococcaceae UCG-005, Anaerovibrio, Bacteroides, and Christensenellaceae_R-7_group were closely correlated with most of physiological data and the differential metabolites following SHYS treatment. In conclusion, our study revealed multiple ameliorative effects of SHYS on DN including the alleviation of hyperglycemia and the improvement of renal function, pathological changes in kidney, oxidative stress, and the inflammatory response. The mechanism of SHYS on DN may be related to the improvement of gut microbiota which regulates arginine biosynthesis, TCA cycle, tyrosine metabolism, and arginine and proline metabolism.

Blue carbon (C) ecosystems (mangroves, salt marshes, and seagrass beds) sequester high amounts of C, which can be respired back into the atmosphere, buried for long periods, or exported to adjacent ecosystems by tides. The lateral exchange of C between a salt marsh and adjacent water is a key factor that determines whether a salt marsh is a C source (i.e., outwelling) or sink in an estuary. We measured salinity, particulate organic carbon (POC), and dissolved organic carbon (DOC) seasonally over eight tidal cycles in a tidal creek at the Chongming Dongtan wetland from July 2017 to April 2018 to determine whether the marsh was a source or sink for estuarine C. POC and DOC fluxes were significantly correlated in the four seasons driven by water fluxes, but the concentration of DOC and POC were positively correlated only in autumn and winter. DOC and POC concentrations were the highest in autumn (3.54 mg/L and 4.19 mg/L, respectively) and the lowest in winter and spring (1.87 mg/L and 1.51 mg/L, respectively). The tidal creek system in different seasons showed organic carbon (OC) export, and the organic carbon fluxes during tidal cycles ranged from –12.65 to 4.04 g C/m2. The intensity showed significant seasonal differences, with the highest in summer, the second in autumn, and the lowest in spring. In different seasons, organic carbon fluxes during spring tides were significantly higher than that during neap tides. Due to the tidal asymmetry of the Yangtze River estuary and the relatively young stage, the salt marshes in the study area acted as a strong lateral carbon source.

For the development of safe and effective EBV (Epstein-Barr virus) vaccines, the Ag85A signal peptide from M. tuberculosis H37Rv was used to construct a recombinant secretory BCG (Bacillus Chalmette-Guérin) plasmid. The Ag85A gene, fused to the EBV LMP2A (latent membrane protein) and hGM-CSF (human granulocyte/macrophage colony-stimulating factor) genes, was inserted into the pMV261 vector (secretory BCG plasmid). The expression levels of the hGM-CSF and LMP2A proteins in rBCG (recombinant BCG) were measured by Western blot analysis. Humoral immunity, cellular immunity, and antitumor effects were determined by a series of experiments. The recombinant pMVGCA plasmid effectively expressed GCA (hGM-CSF and LMP2A fusion protein) in BCG after transformation, and the rBCG proteins were recognized by antibodies against hGM-CSF and LMP2A. Six weeks after immunization, the maximum dose of rBCG resulted in antibody titers of 1:19,800 (hGM-CSF antibody) and 1:21,800 (LMP2A antibody). When the effector:target ratio was 40:1, specific lysis was maximal and approximately two times stronger than that in mice immunized with the control. Tumorigenicity was lower in the rBCG treatment group, with a tumor inhibition rate of 0.81 ± 0.09 compared with the control groups. EB virus-positive tumors are inhibited by rBCG expressing an hGM-CSF and LMP2A fusion protein.

Objective:To explore the clinical presentation and molecular genetic characteristics of a cohort of congenital hyperinsulinism (CHI) patients from southern China and also to explore the most appropriate therapeutic approaches.Methods:We retrospectively reviewed a cohort of 65 children with CHI. Mutational analysis was performed for KCNJ11 and ABCC8 genes. The GLUD1 gene was sequenced in patients with hyperammonaemia. GCK gene sequencing was performed in those patients with no mutation identified in the ABCC8, KCNJ11 or GLUD1 genes.Results:ABCC8 mutations were identified in 16 (25%) of the cohort, GLUD1 mutations were identified in five children, and no KCNJ11 or GCK mutations were identified. Moreover, some unique features of ABCC8 gene mutations in southern Chinese CHI patients were found in this study. The most common mutation was a deletion/insertion mutation p.Thr1042GlnfsX75 was found in five unrelated patients, which possibly represents a relatively common mutation in southern China. Five novel ABCC8 mutations were detected. The mutations were p.Phe5SerfsX72, p.Gln273ArgfsX85, p.Leu724del, p.Asp1447Gly and IVS 25-1G>T. Five compound heterozygous mutations of ABCC8 gene were identified in this study, and three of these patients were diazoxide-responsive. Forty patients were diazoxide-responsive, 13 patients were diazoxide-unresponsive and 12 patients received dietary treatment only. A pancreatectomy was performed in 10 patients who were unresponsive to medical treatment.Conclusion:To the best of our knowledge, this is the first study of CHI in south China. Mutations in ABCC8 are the most common causes of CHI in this cohort. Diazoxide and dietary treatment were effective in most patients. Multicentre studies are necessary to obtain the long-term follow-up characteristics of such patients at a national level.

BackgroundOver the last two decades, the prevalence of colistin resistance among the members of Enterobacteriaceae has been increasing, particularly among Klebsiella pneumoniae isolates; this limits the potential use of colistin and leads to worsened clinical outcomes.MethodsWe investigated the prevalence and genetic characteristics of colistin-resistant K. pneumoniae (COLR-KP) in clinical isolates using genomic sequencing.ResultsIn total, 53 K. pneumoniae isolates (4.5%, 53/1,171) were confirmed as COLR-KP, of which eight isolates carried mobile colistin-resistant (mcr) gene. Although the overall prevalence rate (0.7%, 8/1,171) of mcr-like genes in clinical K. pneumoniae remained relatively low, the presence of mcr (15.1%, 8/53) among the COLR-KP isolates indicated that the mobile resistance gene was already widespread among K. pneumoniae isolates in hospital setting. We randomly selected 13 COLR-KP isolates (four mcr-bearing and nine non-mcr-bearing isolates) for whole-genome sequencing, including two pandrug-resistant and four sequence type 11 (ST11) isolates. Phylogenetic analysis revealed that all COLR-KP isolates were genetically diverse. Among the four mcr-bearing isolates, three (KP4, KP18, and KP30) were positive for mcr-1 and one (KP23) for mcr-8; none of the other mcr genes were detected. The mcr-1 in the KP4 and KP30 isolates were located in an IncX4 plasmid (approximately 33 kb) and could be successfully transferred to Escherichia coli J53AZR. In contrast, for the mcr-8-bearing plasmid in KP23 (IncFII), colistin resistance could not be transferred by conjugation. The mcr-1-producing isolate KP18 coexists a novel plasmid-carried tigecycline resistance gene tmexCD1-toprJ1. The most common chromosomal mutation associated with colistin resistance was a T246A amino acid substitution in PmrB, which was identified in most COLR-KP isolates (11/13, 84.6%). All ST11 isolates additionally had an R256G amino acid substitution. Critical virulence factors associated with hypervirulent K. pneumoniae were detected in four COLR-KP isolates; these virulence factors included aerobactin, salmochelin, and yersiniabactin.ConclusionWe found that mcr-bearing COLR-KP emerged in our hospital and was growing at an increasing rate. Simultaneous emergence of hypervirulence and colistin–tigecycline–carbapenem resistance in the epidemic clone ST11 K. pneumoniae was also observed; this highlights the significance of active and continuous surveillance.

Objective: Preeclampsia affects 2–8% of women and doubles the risk of cardiovascular disease in women after preeclampsia. This study aimed to develop a model based on machine learning to predict postpartum cardiovascular risk in preeclamptic women.Methods: Collecting demographic characteristics and clinical serum markers associated with preeclampsia during pregnancy of 907 preeclamptic women retrospectively, we predicted the cardiovascular risk (ischemic heart disease, ischemic cerebrovascular disease, peripheral vascular disease, chronic kidney disease, metabolic system disease or arterial hypertension). The study samples were divided into training sets and test sets randomly in the ratio of 8:2. The prediction model was developed by 5 different machine learning algorithms, including Random Forest. 10-fold cross-validation was performed on the training set, and the performance of the model was evaluated on the test set.Results: Cardiovascular disease risk occurred in 186 (20.5%) of these women. By weighing area under the curve (AUC), the Random Forest algorithm presented the best performance (AUC = 0.711[95%CI: 0.697–0.726]) and was adopted in the feature selection and the establishment of the prediction model. The most important variables in Random Forest algorithm included the systolic blood pressure, Urea nitrogen, neutrophil count, glucose, and D-Dimer. Random Forest algorithm was well calibrated (Brier score = 0.133) in the test group, and obtained the highest net benefit in the decision curve analysis.Conclusion: Based on the general situation of patients and clinical variables, a new machine learning algorithm was developed and verified for the individualized prediction of cardiovascular risk in post-preeclamptic women.

The at-haulback mortality of swordfish (Xiphias gladius), a highly migratory fish, in the Indian Ocean during tuna longline fishery is a concern of the Indian Ocean Tuna Commission Fisheries Management. We obtained the data of 1144 swordfish recorded in 1925 operations in the Indian Ocean by Chinese tuna longline observers from 2012–2018. A generalized linear model was used to analyze the at-haulback mortality of swordfish and the potential influencing factors. The overall mortality rate of swordfish was 64.0%, and the average female size was 166.3 cm (SD = 32.5 cm), with an observed at-haulback mortality rate of 64.3%. The average male size was 155.1 cm (SD = 25.6 cm), which was smaller than females. The observed at-haulback mortality rate was 63.6%. No significant difference was observed between the sexes. Quarter, longitude, hook type, and Lower Jaw-Fork Length (LJFL) had a significant effect on the at-haulback condition when fish were retrieved onboard. Longitude and LJFL had a significant effect on the at-haulback mortality of swordfish. When the capture position was closer to the east, the at-haulback mortality decreased and LJFL increased. The interaction term of hook type and LJFL had a significant effect on at-haulback mortality. When using the circle hook and other hook types, the greater the LFJL, the greater the mortality rate; the opposite was true for Japanese tuna hooks. We provide information for understanding the at-haulback mortality of swordfish bycatch by Chinese tuna longline fishing fleets in the Indian Ocean and its influencing factors, which will help the future conservation and management of swordfish.

Integrating the flow of supply and demand of ecosystem services (ESs) into the ecological security pattern (ESP) of coastal ecosystems with extremely fragile ecological backgrounds and contradictory human–land relationships is beneficial to the coordinated development of human–land systems. However, existing studies ignore the issue of scales of supply–demand linkages, making the ESP not properly guide sustainable development. Based on ESs delivery chain theory and landscape ecology approaches, we developed a sustainable development framework consisting of coupled microscopic natural–social systems. The method was tested using data from the Liao River Delta. In this study area, the natural supply potential and demand mapping distribution of key ESs were assessed to identify ecological sources in the Liao River Delta, a typical coastal zone in northern China. The resistance surface based on land use type assignment was modified using hydrological connectivity frequency and nighttime light intensity. Ecological corridors were extracted and optimized using a minimum cumulative resistance model and connectivity evaluation. The study found that the high supply area and the high demand reflection area are not consistent in location and supply level. Ecological source areas are evenly distributed, accounting for 12% of the total area. The ecological corridors are mainly concentrated in the west and southeast and do not cross the built-up areas in the east. This ESP framework safeguards the local demand for natural products and the natural potential to maintain services over the longer term and to a larger scale while informing the development of environmental management measures.

Candida auris emerged as a pathogenic species of fungus that causes severe and invasive outbreaks worldwide. The fungus exhibits high intrinsic resistance rates to various first-line antifungals, and the underlying molecular mechanism responsible for its multidrug resistance is still unclear. In this study, a transcriptomic analysis was performed between two C. auris isolates that exhibited different anti-drug patterns by RNA-sequencing, namely, CX1 (anti-drug sensitive) and CX2 (resistant). Transcriptomic analysis results revealed 541 upregulated and 453 downregulated genes in the resistant C. auris strain compared with the susceptible strain. In addition, our findings highlight the presence of potential differentially expressed genes (DEGs), which may play a role in drug resistance, including genes involved in ergosterol and efflux pump biosynthesis such as SNQ2, CDR4, ARB1, MDR1, MRR1, and ERG genes. We also found that Hsp related genes were upregulated for expression in the anti-drug-resistant strain. Biofilm formation and growth conditions were also compared between the two isolates. Our study provides novel clues for future studies in terms of understanding multidrug resistance mechanisms of C. auris strains.

PurposeTo investigate the features and treatment status of children with type 1 diabetes mellitus (T1DM) in China.MethodsWe recruited patients

Objective To investigate the utility of 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/magnetic resonance imaging (PET/MRI) for the preoperative diagnosis of cervical cancer. Methods We retrospectively analyzed 114 patients who were diagnosed with cervical cancer and underwent PET/MRI (n = 59) or PET/computed tomography (PET/CT) (n = 65) before surgery. The maximal standardized uptake value (SUV max ) and mean SUV (SUV mean ) were determined for regions of interest in the resultant radiographic images. Results Relative to PET/CT, 18 F-FDG PET/MRI exhibited higher specificity and sensitivity in defining the primary tumor bounds and higher sensitivity for detection of bladder involvement. The SUV max and SUV mean of PET/MRI were remarkably higher than those of PET/CT as a means of detecting primary tumors, bladder involvement, and the lymph node status. However, no significant differences in these values were detected when comparing the two imaging approaches as a means of detecting vaginal involvement or para-aortic lymph node metastasis. Conclusions These outcomes may demonstrate the capability of 18 F-FDG PET/MRI to clarify preoperative cervical cancer diagnoses in the context of unclear PET/CT findings. However, studies directly comparing SUVs in different lesion types from patients who have undergone both PET/MRI and PET/CT scans are essential to validate and expand upon these findings.

Urbanization has a significant influence on amphibian communities, populations, and individuals because of habitat loss, degradation of habitat quality, and habitat fragmentation. Advertisement calls of anurans are used for communication and play an important role in reproduction; however, how anthropogenic noise and habitat change caused by urbanization affect anuran advertisement calls is less well known. In this study, we examined changes in the advertisement calls of two frog species, the ornamented pygmy frog (Microhyla fissipes) and rice frog (Fejervarya multistriata), during the breeding season along an urban–rural gradient in Shanghai, China. We used the percentage of impervious area (including buildings and roads) in each 2 km-radius landscape to represent the urbanization index of 34 study sites. We then measured five advertisement call parameters (call duration, call interval, call rate, pulse rate, and dominant frequency) of these two species (100 males of F. multistriata and 89 males of M. fissipes) in each study site from May to July in 2020 and 2021. We explored how the urbanization index and other variables (air temperature, snout–vent length and calling situation (one frog species calling, or two frog species calling together)) in each study site affected these call parameters. The results showed that the dominant frequency of M. fissipes was significantly negatively related to urbanization index, and call duration and call interval were significantly negatively related to air temperature; furthermore, call rate and pulse rate were significantly positively related to air temperature, and call duration was also significantly positively related to snout–vent length. For F. multistriata, pulse rate was significantly negatively related to urbanization index, snout–vent length, and situation (two frog species calling together), but significantly positively related to air temperature; by contrast, call interval was significantly positively related to snout–vent length. We suggested that these two frog species had different responses to urbanization, which could help us to better understand the change of anuran breeding behaviors and reproductive life-history strategies in the face of rapid urbanization.