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Abstract Purpose 46,XY disorders of sex development (46,XY DSD) are characterized by incomplete masculinization of genitalia with reduced androgenization. Accurate clinical management remains challenging, especially based solely on physical examination. Targeted next-generation sequencing (NGS) with known pathogenic genes provides a powerful tool for diagnosis efficiency. This study aims to identify the prevalent genetic variants by targeted NGS technology and investigate the diagnostic rate in a large cohort of 46,XY DSD patients, with most of them presenting atypical phenotypes. Methods Two different DSD panels were developed for sequencing purposes, targeting a cohort of 402 patients diagnosed with 46,XY DSD, who were recruited from the Department of Urology at Children’s Hospital, Zhejiang University School of Medicine (Hangzhou, China). The detailed clinical characteristics were evaluated, and peripheral blood was collected for targeted panels to find the patients’ variants. The clinical significance of these variants was annotated according to American College of Medical Genetics and Genomics (ACMG) guidelines. Results A total of 108 variants across 42 genes were found in 107 patients, including 46 pathogenic or likely pathogenic variants, with 45.7%(21/46) being novel. Among these genes, SRD5A2, AR, FGFR1, LHCGR, NR5A1, CHD7 were the most frequently observed. Besides, we also detected some uncommon causative genes like SOS1, and GNAS. Oligogenic variants were also identified in 9 patients, including several combinations PROKR2/FGFR1/CYP11B1, PROKR2/ATRX, PROKR2/AR, FGFR1/LHCGR/POR, FGFR1/NR5A1, GATA4/NR5A1, WNT4/AR, MAP3K1/FOXL2, WNT4/AR, and SOS1/FOXL2. Conclusion The overall genetic diagnostic rate was 11.2%(45/402), with an additional 15.4% (62/402) having variants of uncertain significance. Additionally, trio/duo patients had a higher genetic diagnostic rate (13.4%) compared to singletons (8.6%), with a higher proportion of singletons (15.1%) presenting variants of uncertain significance. In conclusion, targeted gene panels identified pathogenic variants in a Chinese 46,XY DSD cohort, expanding the genetic understanding and providing evidence for known pathogenic genes’ involvement.

Machine Learning (ML), an Artificial Intelligence (AI) technique that includes both Traditional Machine Learning (TML) and Deep Learning (DL), aims to teach machines to automatically learn tasks by inferring patterns from data. It holds significant promise in aiding medical care and has become increasingly important in improving professional processes, particularly in the diagnosis of psoriasis. This paper presents the findings of a systematic literature review focusing on the research and application of ML in psoriasis analysis over the past decade. We summarized 53 publications by searching the Web of Science, PubMed and IEEE Xplore databases and classified them into three categories: (i) lesion localization and segmentation; (ii) lesion recognition; (iii) lesion severity and area scoring. We have presented the most common models and datasets for psoriasis analysis, discussed the key challenges, and explored future trends in ML within this field. Our aim is to suggest directions for subsequent research.

Abstract Shape-memory materials hold great potential to impart medical devices with functionalities useful during implantation, locomotion, drug delivery, and removal. However, their clinical translation is limited by a lack of non-invasive and precise methods to trigger and control the shape recovery, especially for devices implanted in deep tissues. In this study, the application of image-guided high-intensity focused ultrasound (HIFU) heating is tested. Magnetic resonance-guided HIFU triggered shape-recovery of a device made of polyurethane urea while monitoring its temperature by magnetic resonance thermometry. Deformation of the polyurethane urea in a live canine bladder (5 cm deep) is achieved with 8 seconds of ultrasound-guided HIFU with millimeter resolution energy focus. Tissue sections show no hyperthermic tissue injury. A conceptual application in ureteral stent shape-recovery reduces removal resistance. In conclusion, image-guided HIFU demonstrates deep energy penetration, safety and speed.

Abstract Mast cells are phenotypically and functionally heterogeneous, and their state is possibly controlled by local microenvironment. Therefore, specific analyses are needed to understand whether mast cells function as powerful participants or dispensable bystanders in specific diseases. Here, we show that degranulation of mast cells in inflammatory synovial tissues of patients with rheumatoid arthritis (RA) is induced via MAS-related G protein-coupled receptor X2 (MRGPRX2), and the expression of MHC class II and costimulatory molecules on mast cells are upregulated. Collagen-induced arthritis mice treated with a combination of anti-IL-17A and cromolyn sodium, a mast cell membrane stabilizer, show significantly reduced clinical severity and decreased bone erosion. The findings of the present study suggest that synovial microenvironment-influenced mast cells contribute to disease progression and may provide a further mast cell-targeting therapy for RA.

Abstract Excessive host immune responses contribute to severe malaria with high mortality. Here, we show that PRL2 in innate immune cells is highly related to experimental malaria disease progression, especially the development of murine severe malaria. In the absence of PRL2 in myeloid cells, Plasmodium berghei infection results in augmented lung injury, leading to significantly increased mortality. Intravital imaging revealed greater neutrophilic inflammation and NET formation in the lungs of PRL2 myeloid conditional knockout mice. Depletion of neutrophils prior to the onset of severe disease protected mice from NETs associated lung injury, and eliminated the difference between WT and PRL2 CKO mice. PRL2 regulates neutrophil activation and NET accumulation via the Rac-ROS pathway, thus contributing to NETs associated ALI. Hydroxychloroquine, an inhibitor of PRL2 degradation alleviates NETs associated tissue damage in vivo. Our findings suggest that PRL2 serves as an indicator of progression to severe malaria and ALI. In addition, our study indicated the importance of PRL2 in NET formation and tissue injury. It might open a promising path for adjunctive treatment of NET-associated disease.

Eutrophication has become prominent in many lakes of the world, resulting in a continuous rise of suspended particulate organic matter (POM) that can be of vital consequence for water quality and carbon cycling. While the accumulation and decomposition of POM can enhance nutrient cycling at a rate depending on the property of lake-water organic carbon, it is important to identify the source of suspended POM for evaluating eutrophication and carbon burial. Here we analyzed the distribution of stable isotopic ratios (δ13C and δ15N) and the carbon/nitrogen ratio (C/N) in suspended POM in a shallow eutrophic lake of subtropical China, for apportioning the POM sources using Bayesian mixing model. Specifically, we collected seasonal samples of lake-water POM (>0.7 μm) from 20 sites in Yilong Lake from September 2020 to June 2022, as well as six types of modern samples covering the main carbon sources in the catchment. The spatial surveys showed that in the dry year (low water level) the δ13C of POM was more enriched in the western basin than those in the central and eastern basins, while the seasonal surveys showed the most enriched δ13C of POM in September. However, this spatio-temporal heterogeneity disappeared in the wet year (high water level). It was also found that the δ13C, δ15N and C/N values of POM varied significantly with those of phytoplankton across sites and seasons. Application of the MixSIAR model further showed that phytoplankton was the predominant source of POM in Yilong Lake (79.8 ± 13.4 %), but with large annual difference, 68.9 ± 10.3 % in the dry year and 90.7 ± 3.7 % in the wet year. In comparison, the contribution of the other five endmembers was much more moderate. In particular, the proportion of allochthonous organic carbon in POM was relatively low, with terrestrial plants and soils contributing 6.1 ± 4.8 % and 4.3 ± 2.5 % of POM, respectively. Our quantitative evidence for the dominance of the autochthonous source (i.e., phytoplankton) in lake-water POM over time and space suggested a determining role of eutrophication in the composition of lake organic carbon. Therefore, the coupling of algal blooms with organic carbon cycling in inland waters can be enhanced with continuous catchment development and regional warming.

Study region: Changwu Tableland, Chinese Loess Plateau Study focus: Soil water status and water demand are two important factors to influence root water uptake (RWU) patterns, but the mechanisms involved in deep-rooted plants remain unknown. This study addresses this knowledge gap by investigating diurnal variations in RWU patterns for two different-aged apple orchards (7 vs. 19 years) on the Chinese Loess Plateau (CLP). We achieved this by inputting measured plant and soil information into a physical-based numerical RWU model. New hydrological insights for the region: The results showed that the 19-year-old orchard exhibits distinct characteristics compared to the 7-year-old orchard. Specifically, the 19-year-old orchard had less deep soil water content, resulting in lower matric potential and hydraulic conductance. In contrast to cropland soil water, the cumulative deep soil water (>2 m) deficits were 17.6 and 1108.3 mm in the 7-year-old and 19-year-old orchards, respectively. Despite the 19-year-old orchard having 67% of its fine roots below 5 m soil depth, their contribution ratio to total RWU was only 30–40%, indicating less available deep soil water for the older orchard.Sap flow and leaf water potential had bell-shaped diurnal variations, leading to shifting soil water contributions to RWU in the 7-year-old and 19-year-old orchards. These changes were particularly evident when soil water potential in the root zone was heterogeneous, resulting in contrasting RWU patterns during different water demand periods. Notably, the 7-year-old orchard exhibited less water contribution from deep 2–5 m layer and enriched xylem water isotopes at midday with high water demand, while the 19-year-old orchard had more water contribution from deep 5–21.6 m layer and depleted xylem water isotopes. These contrasting RWU variations shed light on the profound impact of orchard age on deep RWU patterns, especially under the varying water demand conditions after CLP afforestation.

With the rapid growth in the number of EVs, a huge number of EVs are connected to the power grid for charging, which places a great amount of pressure on the stable operation of the power grid. This paper focuses on the development of V2G applications, based on the current research status of V2G technology. Firstly, the standards on V2G applications and some pilot projects involving more representative V2G systems are introduced. Comparing V2G applications with ordered charging and unordered charging, the social and economic benefits of V2G applications are highlighted. Analysis of the social benefits of V2G applications concerns three points: the grid demand response, personalized charging, and the coordination of renewable energy sources. And analysis of the economic benefits of V2G applications is divided into three parties: the grid, the aggregator, and individuals. From the perspective of innovative EVs expanding the application scenarios through V2G technology, V2G applications for commercial EVs, emergency power applications, and vehicle-to-vehicle energy trading are introduced. The current challenges related to V2G applications are presented: users’ willingness to participate in V2G applications, battery loss, charging and discharging tariffs, privacy and security, and power loss. Finally, some research recommendations for the development of V2G applications are given and the current state of research in regard to those recommendations is presented.

Summary: Objective: To compare the characteristics of conventional laparoscopic pyeloplasty (LP) and robotic-assisted laparoscopic pyeloplasty (RALP) in infants and young children with ureteropelvic junction obstruction (UPJO). Methods: We performed a retrospective study of patients (age: 0–36 months) who underwent dismembered pyeloplasty (Anderson-Hynes) with the fourth-generation RALP or traditional LP between April 2020 and December 2020. Results: A total of 33 patients with UPJO were enrolled: 12 underwent RALP (9 left side; 3 right side) and 21 underwent LP (18 left side; 3 right side). In the RALP group, the median patient age was 17 months (range: 5–36 months). In the LP group, the median patient age was 9 months (range: 2–36 months) (P = 0.182). The mean operation times were 120.25 ± 37.54 min (RALP) and 156.10 ± 51.11 min (LP) (P = 0.042), and the mean lengths of hospital stay were 6.42 ± 1.62 days (RALP) and 8.19 ± 2.25 days (LP) (P = 0.023). Removal of the drainage tube was performed after 3.08 ± 0.69 days (RALP) and after 4.76 ± 1.81 days (LP) (P = 0.001). The postoperative pain showed no significant difference. The mean hospitalization costs were 61464.75 ± 2800.53 yuan (RALP) and 22169.52 ± 3442.15 yuan (LP) (P

Study region: Xindiangou Watershed in Suide, the Loess Plateau, China Study focus: Deep soil water (DSW) is gradually depleted as vegetation stand age increases, resulting in dried soil layers (DSLs) in the Loess Plateau in China. However, it is unclear whether old-aged vegetation continues to use DSW under DSLs. This study monitored soil water five times (2001, 2005, 2006, 2007, 2020) in the deep profile for three common vegetation types [Pinus tabuliformis Carr. (P. tabuliformis), Caragana korshinskii Kom. (C. korshinskii), Platycladus orientalis L. Franco (P. orientalis)] planted in 1985. In 2020, we measured soil water content, root characteristics, and soil particle composition to investigate DSW status and the influencing factors. New hydrologic insights for the region: Soil water in the 2–10 m soil layer did not significantly differ from 17- to 36-year stand for the three vegetation types (p

Abstract Background Disorders of sex development (DSD) are congenital disorders in which the development of the chromosomal, gonadal, or anatomical sex is atypical. Mutations in various genes can impede gonadal development, hormone synthesis, or hormone function and cause DSD. Methods Exome sequencing was performed for two siblings with 46,XY DSD. All mutations identified by exome sequencing were confirmed by Sanger sequencing. Results The 13-month-old younger sibling had a female appearance of the external genital with a clitoris that was assessed as Prader III and scored 2 in the external masculinization score evaluative test. The 16-year-old elder sibling had severe hypospadias. Exome sequencing revealed compound heterozygous mutations in exon 3 of DHH in the siblings with 46,XY DSD. The frameshift mutation (NM_021044.3: c.602delC) was derived from the father and was predicted to be deleterious. The (c.937G > T) substitution mutation was derived from the mother. Conclusions Novel compound heterozygous mutations of DHH led to 46,XY DSD in two siblings. This study expands the phenotypic mutation spectra of DHH in patients with 46,XY DSD.

The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is an essential component of the human innate immune system, and is closely associated with adaptive immunity. In most cases, the activation of the NLRP3 inflammasome requires priming and activating, which are influenced by various ion flux signals and regulated by various enzymes. Aberrant functions of intracellular NLRP3 inflammasomes promote the occurrence and development of autoimmune diseases, with the majority of studies currently focused on rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis. In recent years, a number of bioactive substances have shown new potentiality for regulating the NLRP3 inflammasome in autoimmune diseases. This review provides a concise overview of the composition, functions, and regulation of the NLRP3 inflammasome. Additionally, we focus on the newly discovered bioactive substances for regulating the NLRP3 inflammasome in autoimmune diseases in the past three years.

Uremic neuropathy in children encompasses a wide range of central nervous system (CNS), peripheral nervous system (PNS), autonomic nervous system (ANS), and psychological abnormalities, which is associated with progressive renal dysfunction. Clinically, the diagnosis of uremic neuropathy in children is often made retrospectively when symptoms improve after dialysis or transplantation, due to there is no defining signs or laboratory and imaging findings. These neurological disorders consequently result in increased morbidity and mortality among children population, making uremia an urgent public health problem worldwide. In this review, we discuss the epidemiology, potential mechanisms, possible treatments, and the shortcomings of current research of uremic neuropathy in children. Mechanistically, the uremic neuropathy may be caused by retention of uremic solutes, increased oxidative stress, neurotransmitter imbalance, and disturbance of the blood-brain barrier (BBB). Neuroimmune, including the change of inflammatory factors and immune cells, may also play a crucial role in the progression of uremic neuropathy. Different from the invasive treatment of dialysis and kidney transplantation, intervention in neuroimmune and targeted anti-inflammatory therapy may provide a new insight for the treatment of uremia.

Abstract Background Splenogondal fusion (SGF) is a rare congenital anomaly characterized by abnormal association between the splenic tissue and the gonads or mesonephric remnants. SGF that requires separate two-stage laparoscopic staged Fowler-Stephen orchiopexy on both the left and right sides is extremely rare. SGF could be misdiagnosed as testicular malignancy and leads to unnecessary orchiectomy. Case presentation This is a case of an 8-month old male infant presented with bilateral cryptorchidism, B-mode ultrasound visualized the left and right testes in the lower abdominal cavity and the upper margin of the left testicle as a hypoechoic mass extending to the spleen, indicating an undescended right testis and possible SGF on the left side. Single-site laparoscopic examination confirmed the diagnosis of SGF on the left side and an undescended right testis. As both testes were high and the right spermatic vessel was poorly developed and short, a routine single stage orchiopexy would be difficult and risky, therefore, separate two-stage laparoscopic staged Fowler-Stephen orchiopexies for both sides were implemented. Stage 1 of the staged Fowler-Stephen orchiopexy for the right side was performed first without treating the left side, Stage 2 for the right side, separation of the left testis from the spleen as well as Stage 1 for the left side were performed 7 months later, and Stage 2 for the left side was performed 7 months after that. Follow-up ultrasound 1 year after the surgery revealed no obvious abnormalities in the shapes of the testes or their blood supply. This treatment strategy prevented unnecessary orchiectomy. Conclusions We reported a rare case of SGF that needed separate two-stage laparoscopic staged Fowler-Stephen orchiopexies for both sides, and a review of the recent literature. SGF is a rare congenital anomaly often diagnosed incidentally during exploration/surgery for scrotal swelling/mass, cryptorchidism or inguinal hernia in young patients. Surgeons, especially pediatric surgeons should be aware of this rare condition to avoid unnecessary, life-altering radical orchiectomy. When routine single stage orchiopexy is not feasible or risky for either side, separate two-stage laparoscopic staged Fowler-Stephen orchiopexies could be performed on both the left and right sides to avoid unnecessary orchiectomy.

Hydrological regulation and land uses are known to alter lake organic carbon stock, while inorganic carbon cycling in karst landscapes may as well be shifted due to its rapid kinetic rate. To date, the synchronous pattern in the variations of sediment organic carbon (TOC) and inorganic carbon (TIC) burial in karst lakes largely remains to be quantified along the gradient of catchment development. Two karst lakes with contrasting nutrient level and water depth from Southwest China, both of which were converted to medium-sized reservoirs in ∼1985, were selected for sediment multi-proxy analyses on the temporal and spatial variation of carbon burial in the last ∼80 years. While hydrological fluctuations were well recorded by the sediment variation of particle size, the gradual decrease in median grain size showed a trend of increasing water depth that is consistent with the damming events for both lakes. Meanwhile, the nutrient variables revealed an acceleration of eutrophication since ∼2000 when a rapid expansion of catchment croplands was documented for both lakes. While diatom assemblage showed a significant response to hydro-climatic fluctuation and nutrients at both lakes, algal production (i.e. chlorophyll and cyanobacterial pigments) significantly increased with eutrophication at both lakes. The TIC content in the mesotrophic Taiping Lake and the TOC content in the eutrophic lake of Sanjiaohai both showed a significant increase with agricultural expansion, however, the contents of TOC in Taiping and of TIC in Sanjiaohai remained relatively stable over time. While a significant increase in the sediment flux with decreasing bulk sediment C:N ratios suggests elevated autochthonous input, the temporal change of TIC and TOC flux showed a significant synchrony at both lakes. Meanwhile, the sediment content and flux of TIC is significantly higher than those of TOC in Taiping Lake with a higher rate of carbon turnover, but lower than those of TOC in Sanjiaohai. Thus, the accumulation of TIC was disproportionally promoted in deep lakes while the burial of TOC is more favorable in eutrophic and shallow lakes. Overall, our sediment evidence highlights that agricultural expansion and hydrological regulation could interact in altering the sediment stock of TIC and TOC, and their synchronous variation in Karst landscapes.

In this multi-proxy palaeo study, the response of primary producers and consumers to anthropogenic disturbances in a large shallow lake was investigated. Overall, eutrophication and water-level changes (partly inferred by bisaccate pollen grains) are well-reflected in changes in sedimentation rates of pigments, diatom and cladoceran species composition and other proxies (e.g. Rhabdocoela oocytes). In particular, the stepwise decrease in relative abundance of Pediastrum simplex compared to P. boryanum/P. duplex proved to be a good indicator for eutrophication intensity. Furthermore, reductions in the body size (i.e. coenobia diameter) of Pediastrum simplex were clearly related to phases of low visibility that were caused by lake damming in the 1950 s and by accelerating eutrophication in the 1990 s. During the latter period, strong algal growth led to turbid conditions, which are indicated by the co-occurrence of the diatoms Fragilaria crotonensis, Aulacoseira ambigua and A. granulata, the green algae Staurastrum sp. as well as the cladoceran Anthalona cf. milleri. This study highlights that subfossil remains, which are often found in, for instance, standard cladoceran analysis (green algae such as Pediastrum spp. and Staurastrum spp. or bisaccate pollen grains), can add valuable information to the reconstruction of past environmental conditions and biotic response. Such better and more holistic understanding of freshwater ecosystems is crucial to meet future challenges in a rapidly changing world.

Abstract High levels of ROS cause oxidative stress, which plays a critical role in cell death. As a ROS effector protein, PRL2 senses ROS and controls phagocyte bactericidal activity during infection. Here we report PRL2 regulates oxidative stress induced cell death. PRL2 senses oxidative stress via highly reactive cysteine residues at 46 and 101. The oxidation of PRL2 causes protein degradation and supports pro-survival PDK1/AKT signal which in turn to protect cells against oxidative stress. As a result, PRL2 levels have a high correlation with oxidative stress induced cell death. In vivo experiments showed PRL2 deficient cells survive better in inflammatory oxidative environment and resist to ionizing radiation. Our finding suggests PRL2 serves as a negative regulator in cell adaptation to oxidative stress. Therefore, PRL2 could be targeted to modulate cell viability in inflammation or irradiation associated therapy.

CD4+ T cells play a vital role in the adaptive immune system and are involved in the pathogenesis of many diseases, including cancer, autoimmune diseases, and chronic inflammation. As an important mechanism for energy storage, a lot of researches have clarified that metabolism imbalance interacts with immune disorder, and one leads to the other. Lipid metabolism has close relationship with CD4+ T cells. In this review, we discuss fatty acid, cholesterol, prostaglandin, and phospholipid metabolism in CD4+ T cell subsets. Fatty acid β-oxidation (FAO) is activated in Th17 cell to support the proinflammatory function. Cholesterol promotes Th1, Th2, and Treg cell differentiation. In addition to glucose metabolism, lipid metabolism is also very important for immunity. Here, it is highlighted that lipid metabolism regulates CD4+ T cell differentiation and function and is related to diseases.

Schistosome infection contributes to cancer development, but the mechanisms are still not well-understood. SjE16.7 is an EF-hand calcium-binding protein secreted from Schistosoma japonicum eggs. It is a neutrophil attractant and macrophage activator and, as such, plays an important role in the inflammatory granuloma response in schistosomiasis. Here, we show that SjE16.7 binds to host cells by interacting with receptors for advanced glycation end products (RAGE). This ligation leads to activation of the NF-κB signaling pathway, an increase in the generation of reactive oxygen species, and production of the pro-inflammatory cytokines IL-6 and TNF-α. Using a mouse model of colorectal cancer, we demonstrate that intraperitoneal injection of SjE16.7 promotes colorectal cancer progression along with systemic myeloid cell accumulation. Thus, our results identify a new helminth antigen contributing to tumor development in the mammalian host.

Rheumatoid arthritis (RA) is a common autoimmune disease with characteristics of synovial inflammation, pannus formation, cartilage destruction, and bone erosion. Further, the inflammation is linked to increased oxygen consumption, resulting in hypoxia within the inflammatory area. Hypoxia-inducible factor (HIF) was reported to be associated with adaptation to the hypoxic microenvironment in the RA synovium. Here, we have briefly summarized the structure and expression of HIF. Moreover, the function of HIF in inflammation, angiogenesis, cartilage damage, and immune cells of RA has been discussed.

Abstract Rheumatoid arthritis (RA) is a systemic autoimmune disease that results in a chronic and inflammatory disorder. Dynamic balance of helper T cells (Th) 1 and 17 and regulatory T cells (Treg) is broken in RA. Since there is no cure for RA at present, it is necessary to find a truly effective and convenient treatment. Several studies have intended to induce ergotopic regulation to treat autoimmune diseases. This study was undertaken to find potential ergotope peptides and investigate their effects in treating the animal model of RA and their underlying regulatory mechanisms. First, we selected functional ergotope peptides from 25 overlapping peptides derived from the interleukin 2 receptor (IL-2R) α chain, and then used these peptides to treat collagen-induced arthritis (CIA). We showed ergotope peptides as immunomodulatory factors with great benefits at the clinical and pathologic levels. This effect was associated with inhibition of type II collagen (CII)-specific proliferation and autoantibody production as well as induction of antiergotypic immune response, downregulation of both Th1 and Th17 cells and their related components, and emergence of Treg cells that had suppressive action on autoreactive T cells. We also proved that cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and IL-10 are two important mediators that are critical to Treg suppressive function. Inhibition of Th1 and Th17 in established CIA could be attributed to ergotope-induced Treg cells. Our findings reveal that ergotope peptides induce regulatory immune responses and restore immune tolerance, suggesting that treatment with ergotope peptides may be a novel approach to therapy for RA patients and has good application prospects, with cheap, effective, convenient, wide-spectrum features.

Inland lake variations are considered sensitive indicators of global climate change. However, human activity is playing as a more and more important role in inland lake area variations. Therefore, it is critical to identify whether anthropogenic activity or natural events is the dominant factor in inland lake surface area change. In this study, we proposed a method that combines the Douglas-Peucker simplification algorithm and the bend simplification algorithm to locate major lake surface area disturbances. These disturbances were used to extract the features that been used to classify disturbances into anthropogenic or natural. We took the nine lakes in Yunnan Province as test sites, a 31-year long (from 1987 to 2017) time series Landsat TM/OLI images and HJ-1A/1B used as data sources, the official records were used as references to aid the feature extraction and disturbance identification accuracy assessment. Results of our method for disturbance location and disturbance identification could be concluded as follows: (1) The method can accurately locate the main lake changing events based on the time series lake surface area curve. The accuracy of this model for segmenting the time series of lake surface area in our study area was 94.73%. (2) Our proposed method achieved an overall accuracy of 87.75%, with an F-score of 85.71 for anthropogenic disturbances and an F-score of 88.89 for natural disturbances. (3) According to our results, lakes in Yunnan Province of China have undergone intensive disturbances. Human-induced disturbances occurred almost twice as much as natural disturbances, indicating intensified disturbances caused by human activities. This inland lake area disturbance identification method is expected to uncover whether a disturbance to inland lake area is human activity-induced or a natural event, and to monitor whether disturbances of lake surface area are intensified for a region.

Although it is well-recognized that inflammation enhances leukocyte bactericidal activity, the underlying mechanisms are not clear. Here we report that PRL2 is sensitive to oxidative stress at inflamed sites. Reduced PRL2 in phagocytes causes increased respiratory burst activity and enhances phagocyte bactericidal activity. PRL2 (Phosphatase Regenerating Liver 2) is highly expressed in resting immune cells, but is markedly downregulated by inflammation. in vitro experiments showed that PRL2 was sensitive to hydrogen peroxide (H2O2), a common damage signal at inflamed sites. In response to infection, PRL2 knockout (KO) phagocytes were hyper activated, produced more reactive oxygen species (ROS) and exhibited enhanced bactericidal activity. Mice with PRL2 deficiency in the myeloid cell compartment were resistant to lethal listeria infection and cleared the bacteria more rapidly and effectively. Moreover, in vitro experiments demonstrated that PRL2 binds to GTPase Rac and regulates ROS production. Rac GTPases were more active in PRL2 (KO) phagocytes than in wild type cells after bacterium infection. Our findings indicate that PRL2 senses ROS at inflamed sites and regulates ROS production in phagocytes. This positive feedback mechanism promotes bactericidal activity of phagocytes and may play an important role in innate anti-bacterial immunity.

Polyploid species generally occupy harsher habitats (characterized by cold, drought and/or high altitude) than diploids, but the converse was observed for Chamerion angustifolium, in which diploid plants generally inhabit higher altitudes than their polyploid derivatives. Plants at high altitudes may experience cold-induced water stress, and we therefore examined the physiological responses of diploid and hexaploid C. angustifolium to water stress to better understand the ecological differentiation of plants with different ploidy levels. We conducted a common garden experiment by subjecting seedlings of different ploidy levels to low, moderate and severe water stress. Fourteen indicators of physiological fitness were measured, and the anatomical characteristics of the leaves of each cytotype were determined. Both cytotypes were influenced by drought, and diploids exhibited higher fitness in terms of constant root:shoot ratio (R:S ratio) and maximum quantum yield of PSⅡ (Fv/Fm), less reduced maximal photosynthetic rate (Amax), transpiration rate (E), intercellular CO2 concentration (Ci) and stomatal conductance (gs), and higher long-term water use efficiency (WUEL) under severe water stress than did hexaploids. Analysis of leaf anatomy revealed morphological adjustments for tolerating water deficiency in diploids, in the form of closely packed mesophyll cells and small conduits in the midvein. Our results indicate that diploid C. angustifolium is more tolerant of drought than hexaploid plants, ensuring the successful survival of the diploid at high altitudes. This eco-physiological divergence may facilitate the species with different cytotypes to colonize new and large geographic ranges with heterogeneous environmental conditions.

Multiple sclerosis is the most common autoimmune disease of the central nervous system. It is believed that the increased migration of autoreactive lymphocytes across the blood-brain barrier (BBB) may be responsible for axonal demyelination of neurons. In this review, we discuss microRNAs participating in the pathological processes of MS, including periphery inflammation, blood-brain barrier disruption, and CNS lesions, and in its therapeutic response, in order to find biomarkers of disease severity and to predict the response to therapy of the diseases.

Mast cells are important in innate immune system. They have been appreciated as potent contributors to allergic reaction. However, increasing evidence implicates the important role of mast cells in autoimmune disease like rheumatoid arthritis and multiple sclerosis. Here we review the current stage of knowledge about mast cells in autoimmune diseases.

Objective. To expand upon the role of iguratimod (T-614) in the treatment of rheumatoid arthritis (RA), we investigated whether the Th1, Th17, follicular helper T cells (Tfh), and regulatory T cells (Treg) imbalance could be reversed by iguratimod and the clinical implications of this reversal. Methods. In this trial, 74 patients were randomized into iguratimod-treated (group A) and control (broup B) group for a 24-week treatment period. In the subsequent 28 weeks, both groups were given iguratimod. Frequencies of Th1, Th17, Tfh, and Treg were quantified using flow cytometry, and serum cytokines were detected by enzyme-linked immunosorbent assay. mRNA expression of cytokines and transcriptional factor were quantified by RT-PCR. The composite Disease Activity Score, erythrocyte sedimentation rate, and C-reactive protein were assessed at each visit. Result. The clinical scores demonstrated effective suppression of disease after treatment with iguratimod. In addition, iguratimod downregulated Th1, Th17-type response and upregulated Treg. Furthermore, the levels of Th1, Th17, and Tfh associated inflammatory cytokines and transcription factors were reduced after treatment with iguratimod, while the levels of Treg associated cytokines and transcription factors were increased.

Sediments from Xinyun Lake in central Yunnan, southwest China, provide a record of environmental history since the Holocene. With the application of multi-proxy indicators (total organic carbon (TOC), total nitrogen (TN), δ13C and δ15N isotopes, C/N ratio, grain size, magnetic susceptibility (MS) and CaCO3 content), as well as accelerator mass spectrometry (AMS) 14C datings, four major climatic stages during the Holocene have been identified in Xingyun's catchment. A marked increase in lacustrine palaeoproductivity occurred from 11.06 to 9.98 cal. ka BP, which likely resulted from an enhanced Asian southwest monsoon and warm-humid climate. Between 9.98 and 5.93 cal. ka BP, a gradually increased lake level might have reached the optimum water depth, causing a marked decline in coverage by aquatic plants and lake productivity of the lake. This was caused by strong Asian southwest monsoon, and coincided with the global Holocene Optimum. During the period of 5.60-1.35 cal. ka BP, it resulted in a warm and dry climate at this stage, which is comparable to the aridification of India during the mid- and late Holocene. The intensifying human activity and land-use in the lake catchment since the early Tang Dynasty (∼1.35 cal. ka BP) were associated with the ancient Dian culture within Xingyun's catchment. The extensive deforestation and development of agriculture in the lake catchment caused heavy soil loss. Our study clearly shows that long-term human activities and land-use change have strongly impacted the evolution of the lake environment and therefore modulated the sediment records of the regional climate in central Yunnan for more than one thousand years.

Multiple sclerosis is an autoimmune disease with classical traits of demyelination, axonal damage, and neurodegeneration. The migration of autoimmune T cells and macrophages from blood to central nervous system as well as the destruction of blood brain barrier are thought to be the major processes in the development of this disease. Chemokines, which are small peptide mediators, can attract pathogenic cells to the sites of inflammation. Each helper T cell subset expresses different chemokine receptors so as to exert their different functions in the pathogenesis of MS. Recently published results have shown that the levels of some chemokines and chemokine receptors are increased in blood and cerebrospinal fluid of MS patients. This review describes the advanced researches on the role of chemokines and chemokine receptors in the development of MS and discusses the potential therapy of this disease targeting the chemokine network.

Rheumatoid arthritis (RA) is a common autoimmune disease with unknown etiology and pathogenesis. Although major therapeutic advances have been made in recent years, there is no cure for the disease. Current medications mainly reduce inflammation in order to relieve pain and slow joint damage, but many have potentially serious side effects. Therefore, to find specific biomarkers will benefit both RA patients to find relief from the disease and physicians to monitor the disease development. A number of biomarkers have been discovered and used clinically, and others are still under investigation. The autoantibodies, which are widely used in diagnosis and prognosis, novel biomarkers, which reflect clinical disease activity, and newly found biomarkers and pathogenic-related cytokines are discussed in this review.

The aim of this study is to determine whether the regulatory role of T cell vaccination (TCV) is through inhibition of Th1/Th17/Tfh and production of autoantibodies on collagen-induced arthritis (CIA). First, CIA mice were treated with TCV. After disease onset, the incidence and severity of change in joint histopathology were evaluated. Mice in the TCV-treated group showed less disease severity and less infiltration of inflammatory cells in the joint sections. TCV decreased the frequencies of Th1/Th17/Tfh cells and related cytokines. Reduction of IL-21 may be associated with both Tfh and Th17, which further influence B cell and T cell responses. In addition, inhibition of Th1/Th17/Tfh frequencies led to the reduced expression of T-bet, RORα, RORγt, and Bcl6. Lastly, the proliferation of type-II-collagen-(CII-) specific T cells and the production of anti-CII antibodies were inhibited in the TCV-treated group. The results provide novel evidence that the therapeutic effects of TCV on CIA are associated with the inhibition of Th1/Th17/Tfh frequencies and autoantibodies production.

Microbes are key components of aquatic ecosystems and play crucial roles in global biogeochemical cycles. However, the spatiotemporal dynamics of planktonic microbial community composition in riverine ecosystems are still poorly understood. In this study, we used denaturing gradient gel electrophoresis of PCR-amplified 16S and 18S rRNA gene fragments and multivariate statistical methods to explore the spatiotemporal patterns and driving factors of planktonic bacterial and microbial eukaryotic communities in the subtropical Jiulong River, southeast China. Both bacterial and microbial eukaryotic communities varied significantly in time and were spatially structured according to upper stream, middle-lower stream and estuary. Among all the environmental factors measured, water temperature, conductivity, PO4-P and TN/TP were best related to the spatiotemporal distribution of bacterial community, while water temperature, conductivity, NOx-N and transparency were closest related to the variation of eukaryotic community. Variation partitioning, based on partial RDA, revealed that environmental factors played the most important roles in structuring the microbial assemblages by explaining 11.3% of bacterial variation and 17.5% of eukaryotic variation. However, pure spatial factors (6.5% for bacteria and 9.6% for eukaryotes) and temporal factors (3.3% for bacteria and 5.5% for eukaryotes) also explained some variation in microbial distribution, thus inherent spatial and temporal variation of microbial assemblages should be considered when assessing the impact of environmental factors on microbial communities.

Aim: The present study aimed to assess the diagnostic efficacy of contrast-enhanced voiding urosonography (ceVUS) using SonoVue for evaluating duplex kidneys, and to compare it with fluoroscopic voiding cystourethrography (VCUG). Material and methods: Forty-six children with duplex kidneys confirmed by surgical intervention or cystoscopy were included in the study, resulting in a total of 46 duplex kidneys and 46 normal kidneys (138 pyeloureteral units). Results: The overall sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of RBUS for diagnosing duplex kidney disease were 73.91%, 80.43%, 79.07%, and 75.51%, respectively. The diagnostic performance of RBUS and ceVUS in detecting duplex kidney yielded an overall sensitivity, specificity, PPV, and NPV of 89.13%, 84.78%, 85.42%, and 88.64%, respectively. The sensitivity, specificity, PPV, and NPV of VCUG in diagnosing duplex kidney disease were 17.31%, 86.96%, 57.14%, and 51.23%, respectively. For the 42 pyeloureteral units with VUR, Cohen's weighted kappa value for the agreement between ceVUS and VCUG in grading VUR was 0.702 (95% CI, 0.551 ~ 0.854; p <0.05). Conclusions: RBUS effectively diagnoses duplex kidneys with renal pelvic dilation, while ceVUS can further elucidate whether reflux occurs in the upper or lower moiety in cases of duplex kidneys with VUR. Compared to VCUG, both RBUS and ceVUS provide more intuitive diagnoses for duplex kidneys with VUR and ureterocele. Additionally, there is good consistency between ceVUS and VCUG in grading VUR. CeVUS is recommended as an initial evaluation method for patients suspected of having duplex kidneys associated with urinary tract infections. [ABSTRACT FROM AUTHOR]