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Summary: Cryptorchidism, commonly known as undescended testis, affects 1%–9% of male newborns, posing infertility and testis tumor risks. Despite its prevalence, the detailed pathophysiology underlying male infertility within cryptorchidism remains unclear. Here, we profile and analyze 46,644 single-cell transcriptomes from individual testicular cells obtained from adult males diagnosed with cryptorchidism and healthy controls. Spermatogenesis compromise in cryptorchidism links primarily to spermatogonium self-renewal and differentiation dysfunctions. We illuminate the involvement of testicular somatic cells, including immune cells, thereby unveiling the activation and degranulation of mast cells in cryptorchidism. Mast cells are identified as contributors to interstitial fibrosis via transforming growth factor β1 (TGF-β1) and cathepsin G secretion. Furthermore, significantly increased levels of secretory proteins indicate mast cell activation and testicular fibrosis in the seminal plasma of individuals with cryptorchidism compared to controls. These insights serve as valuable translational references, enriching our comprehension of testicular pathogenesis and informing more precise diagnosis and targeted therapeutic strategies for cryptorchidism.

Abstract Background Stem cell transplantation shows great potential to improve the long-term survival of cirrhosis patients. However, therapeutic effects may not be homogeneous across the whole study population. This study constructed an easy-to-use nomogram to improve prognostic prediction and aid in treatment decision making for cirrhotic patients. Methods From August 2005 to April 2019, 315 patients with decompensated cirrhosis receiving autologous peripheral blood stem cell (PBSC) transplantation were enrolled in this study. They were randomly classified into training (2/3) and validation (1/3) groups. A predictive model was developed using Cox proportional hazard models and subsequently validated. The predictive performance of the model was evaluated and also compared with other prognostic models. Results Age, creatinine, neutrophil-to-lymphocyte ratio, and Child–Turcotte–Pugh class were included in the nomogram as prognostic variables. The nomogram showed high discrimination power concerning the area under receiver operating characteristic curves (3/5-year AUC: 0.742/0.698) and good consistency suggested by calibration plots. Patients could be accurately stratified into poor- and good-outcome groups regarding liver-transplantation free survival after receiving PBSC therapy (P

Abstract Methods to detect cellular senescence have become increasingly important, even more so in living animals and humans. This cellular state has been found to play fundamental roles in physiological processes as well as functioning detrimentally toward the advent or progression of pathological conditions. Importantly, the study of senescence involvement in these processes in vivo cannot be done without living‐friendly technologies enabling senescence detection. Furthermore, senotherapies or therapies that selectively kill senescent cells have emerged as a new therapeutic strategy for aging and age‐related diseases such as atherosclerosis, cancer, and neurodegenerative disorders and require tools to evaluate their use in vivo. As of now, our in vivo senescence detection toolkit includes genetically engineered reporter mouse models and small molecule imaging probes. Herein, we will focus on the detection of senescence in vivo, including a summary of its challenges, current detection methods and strategies, and a perspective on overcoming the current obstacles.

Background: TBC1 domain family member 20 (TBC1D20) is important in male reproductive, eye lens function and neural system development. However, the role of TBC1D20 on reproduction in female mice remain unclear. Methods: As a prospective laboratory-based study, a mouse model with spontaneous functional mutations of Tbc1d20 (Tbc1d20-⁣/-) was employed to investigate the effect of Tbc1d20 on the fertility of female. Then the role of Tbc1d20 on postnatal female reproductive tract development and gonadal function was measured by immunohistochemistry assay and radioimmunoassay. A bilateral ovarian removal model and an artificial induced decidualization model were employed to reveal the function of Tbc1d20 on endometrial decidualization in vivo. Primary uterine stromal cells were isolated to evaluate the effect of Tbc1d20 on uterine stromal cell proliferation and the ability of decidualization in vitro. Results: Female Tbc1d20-⁣/- mice were infertile. Functional mutations of Tbc1d20 exerted no obvious changes on the function of ovary, structure of fallopian tubes, and ability of early embryo implantation. However, Tbc1d20-⁣/- mice presented marked reduction on the uterine size and weight at two-month-old, accompanied limitations on the myometrial thickness, the number of endometrial glands, and the density of blood vessels. Tbc1d20-⁣/- mice exhibited an impaired uterine decidualization phenotype in vivo. In addition, in vitro primary cell model indicated that the proliferation and differentiation of uterine stromal cells were retarded while Tbc1d20 loss of function. Mechanically, TBC1D20 deficiency triggered endoplasmic reticulum stress in proliferating and differentiating uterine stromal cells. Conclusions: The findings from this study indicated that TBC1D20 is necessary for normal postnatal uterine development and endometrial decidualization in mice.

Objective: The choice of chemotherapeutic regimen for triple-negative breast cancer (TNBC) remains controversial. Homologous recombination deficiency (HRD) has attracted increasing attention in informing chemotherapy treatment. This study was aimed at investigating the feasibility of HRD as a clinically actionable biomarker for platinum-containing and platinum-free therapy. Methods: Chinese patients with TNBC who received chemotherapy between May 1, 2008 and March 31, 2020 were retrospectively analyzed with a customized 3D-HRD panel. HRD positivity was defined by an HRD score ≥ 30 or deleterious BRCA1/2 mutation. A total of 386 chemotherapy-treated patients with TNBC were screened from a surgical cohort (NCT01150513) and a metastatic cohort, and 189 patients with available clinical and tumor sequencing data were included. Results: In the entire cohort, 49.2% (93/189) of patients were identified as HRD positive (40 with deleterious BRCA1/2 mutations and 53 with BRCA1/2 intact with an HRD score of ≥ 30). In the first-line metastatic setting, platinum therapy was associated with longer median progression-free survival (mPFS) than platinum-free therapy [9.1 vs. 3.0 months; hazard ratio (HR), 0.43; 95% confidence interval 0.22–0.84; P = 0.01]. Among HRD-positive patients, the mPFS was significantly longer in those treated with platinum rather than platinum-free therapy (13.6 vs. 2.0 months; HR, 0.11; P = 0.001). Among patients administered a platinum-free regimen, HRD-negative patients showed a PFS significantly superior to that of HRD-positive patients (P = 0.02; treatment-biomarker P-interaction = 0.001). Similar results were observed in the BRCA1/2-intact subset. In the adjuvant setting, HRD-positive patients tended to benefit more from platinum chemotherapy than from platinum-free chemotherapy (P = 0.05, P-interaction = 0.02). Conclusions: HRD characterization may guide decision-making regarding the use of platinum treatment in patients with TNBC in both adjuvant and metastatic settings.

We propose a novel micro-nano structure that can realize a photonic nanojet (PNJ) switch by adjusting the temperature, which is composed of a truncated cylinder coated with a thin vanadium dioxide (VO2) film. The influence of temperature on the maximum strength, full width at half maximum (FWHM), working distance, and focal length of the PNJ were studied by finite-difference time-domain (FDTD) method. The results demonstrate that the structure can adjust the open and close state of the PNJ by changing the temperature. A PNJ with varying characteristics can be obtained at both high and low temperatures, and the maximum intensity ratio of the PNJ can reach up to 7.25. This discovery provides a new way of optical manipulation, sensing and detection, microscopy imaging, optoelectronic devices, and other fields.

Abstract Background Despite emerging evidence on the therapeutic potential of mesenchymal stem cells (MSCs) for liver fibrosis, the underlying mechanisms remain unclear. At present, MSC-derived exosomes (MSC-EXOs) are widely accepted as crucial messengers for intercellular communication. This study aimed to explore the therapeutic effects of MSC-EXOs on liver fibrosis and identify the mechanisms underlying the action of MSC-EXOs. Methods Carbon tetrachloride was used to induce a liver fibrosis model, which was intravenously administered with MSCs or MSC-EXOs to assess treatment efficacy. The resulting histopathology, fibrosis degree, inflammation and macrophage polarization were analyzed. RAW264.7 and BMDM cells were used to explore the regulatory effects of MSC-EXOs on macrophage polarization. Then, the critical miRNA mediating the therapeutic effects of MSC-EXOs was screened via RNA sequencing and validated experimentally. Furthermore, the target mRNA and downstream signaling pathways were elucidated by luciferase reporter assay, bioinformatics analysis and western blot. Results MSCs alleviated liver fibrosis largely depended on their secreted exosomes, which were visualized to circulate into liver after transplantation. In addition, MSC-EXOs were found to modulate macrophage phenotype to regulate inflammatory microenvironment in liver and repair the injury. Mechanically, RNA-sequencing illustrates that miR-148a, enriched in the MSC-EXOs, targets Kruppel-like factor 6 (KLF6) to suppress pro-inflammatory macrophages and promote anti-inflammatory macrophages by inhibiting the STAT3 pathway. Administration of miR-148a-enriched MSC-EXOs or miR-148a agomir shows potent ameliorative effects on liver fibrosis. Conclusions These findings suggest that MSC-EXOs protect against liver fibrosis via delivering miR-148a that regulates intrahepatic macrophage functions through KLF6/STAT3 signaling and provide a potential therapeutic target for liver fibrosis.

Little is known about the association between efficacy of neoadjuvant chemotherapy (NACT)/survival and the dynamic change of tumor immune environment (TIME) during treatment in epithelial ovarian cancer (EOC). This study investigated the TIME landscape of treatment-naive EOC tumors using multiplex immunofluorescence and associated the TIME before and after platinum-based NACT with treatment efficacy and prognosis in 33 patients with advanced EOC. NACT significantly increased the density of CD8+ T cells (P = 0.033), CD20+ B cells (P = 0.023), CD56 NK cells (P = 0.041), PD-1+ cells (P = 0.042), and PD-L1+CD68+ macrophages (P = 0.005) in the tissue specimens. Response to NACT was evaluated using CA125 response and chemotherapy response score (CRS). Compared with the non-responders, the responders displayed a larger proportion of tumors showing increase in the infiltration of CD20+ cells (P = 0.046) and in the M1/M2 ratio (P = 0.038) as well as fewer tumors showing increase in the infiltration of CD56bright cells (P = 0.041). No association was found between pre-NACT TIME and response to NACT. Density of pre-NACT CD8+ cells was positively associated with longer progression-free survival (PFS) (P = 0.011) and overall survival (OS) (P = 0.048). Post-NACT CD20+ and CD163+ macrophages (M2) infiltrates were associated with prolonged (P = 0.005) and shortened PFS (P = 0.021), respectively. Increase in the density of CD4+ T cells was predictive for longer PFS (P = 0.022) and OS (P = 0.023). In the multivariate analysis, high density of CD8+ cells pre-NACT (P = 0.042) were independently associated with improved OS.

Many researchers have reported that inter-yarn friction has an important effect on the response of the plain-weave fabric to an impact. However, the effects of inter-yarn friction on impact responses of woven fabrics with other weaves have not been studied in detail. In the present work, numerical analysis was utilized to study the effects of inter-yarn friction on responses of woven fabrics with different weaves (the plain weave, 2/2 twill, 2/2 basket, and 3/1 twill) to a low-velocity impact. Both inter-yarn friction and the weaves of the woven fabrics greatly influenced the responses of the fabrics to a low-velocity impact. The higher the inter-yarn friction, the higher the levels of the tensile stresses concentrated near the centers of impact of the woven fabrics, and the earlier the failures of the fabrics. In addition, the greater the inter-yarn friction, the higher the velocities of the transverse stress waves in the woven fabrics, and the more effective the distributions of impact energy from the primary yarns of the fabrics to the secondary yarns of the fabrics. Although it had the lowest velocity of the transverse stress wave, due to its firmly interlaced yarns, the plain-weave fabric had the highest total energy absorption capacity among the woven fabrics with the different weaves. On the other hand, due to its loosely interlaced yarns, the 3/1 twill fabric had the lowest total energy absorption capacity among the woven fabrics.

Abstract Spermiogenesis is a complex process depending on the sophisticated coordination of a myriad of testis-enriched gene regulations. The regulatory pathways that coordinate this process are not well understood, and we demonstrate here that AXDND1, as a novel testis-enriched gene is essential for spermiogenesis and male fertility. AXDND1 is exclusively expressed in the round and elongating spermatids in humans and mice. We identified two potentially deleterious mutations of AXDND1 unique to non‐obstructive azoospermia (NOA) patients through selected exonic sequencing. Importantly, Axdnd1 knockout males are sterile with reduced testis size caused by increased germ cell apoptosis and sloughing, exhibiting phenotypes consistent with oligoasthenoteratozoospermia. Axdnd1 mutated late spermatids showed head deformation, outer doublet microtubules deficiency in the axoneme, and loss of corresponding accessory structures, including outer dense fiber (ODF) and mitochondria sheath. These phenotypes were probably due to the perturbed behavior of the manchette, a dynamic structure where AXDND1 was localized. Our findings establish AXDND1 as a novel testis-enrich gene essential for spermiogenesis and male fertility probably by regulating the manchette dynamics, spermatid head shaping, sperm flagellum assembly.

ObjectiveTumor immune microenvironmental features may predict survival and guide treatment. This study aimed to comprehensively decipher the immunological features of different molecular subtypes of endometrial cancer.MethodsIn this retrospective study, 26 patients with primary endometrial cancer and four with recurrent disease treated in our center from December 2018 to November 2021 were included. Next-generation sequencing was performed on tumor samples. Patients were classified into four subtypes, including POLE mutant, microsatellite instability high (MSI-H), no specific molecular profile (NSMP) and TP53 mutant subtypes. Tumor-infiltrating immune cells were quantified using multiplex immunofluorescence assays.ResultsOf the 26 primary endometrial cancer cases, three were POLE mutant, six were MSI-H, eight were NSMP and nine were TP53 mutant. Of the four recurrent cases, two belonged to the NSMP subtype and two belonged to the TP53 mutant subtype. The tumor mutation burden (TMB) levels of POLE mutant and MSI-H cases were significantly higher than that of the other two subtypes (p< 0.001). We combined POLE mutant and MSI-H subtypes into the TMB high (TMB-H) subtype. The TMB-H subtype showed a high degree of infiltration of CD8+ T cells. In the NSMP subtype, the overall degree of intra-tumoral infiltrating immune cells was low. In the TP53 mutant subtype, the densities of both PD-L1+ macrophages (p = 0.047) and PD-1+ T cells (p = 0.034) in tumor parenchyma were the highest among the four subtypes.ConclusionEndometrial cancer of TMB-H, NSMP and TP53 mutant subtypes displayed phenotypes of normal immune response, absence of immune infiltration, and suppressed immune response, respectively. These features may provide mechanistic explanations for the differences in patients’ prognosis and efficacy of immune checkpoint blockade therapies among different endometrial cancer subtypes.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. This tumor presents with an insidious onset, rapid progression, and frequent recurrence. Ferroptosis is a newly discovered mode of programmed cell death that may play a key role in the progression of HCC. This study aimed to investigate the prognostic value of ferroptosis-related genes (FRGs) in HCC and their impact on tumor immune function, thereby providing new insights into targeted therapy for HCC. First, 43 differentially expressed FRGs were identified using the TCGA database, and four prognostically relevant methylation-driven FRGs (G6PD, HELLS, RRM2, and STMN1) were screened via survival and methylation analyses. Gene co-expression, mutation, and clinicopathological characterization indicated that these four pivotal FRGs play essential roles in tumor progression. We also validated these four genes using transcriptomic and proteomic data as well as cohort samples from our patients. Moreover, receiver operator characteristic (ROC) curves confirmed that the signatures of the four FRGs were independent prognostic factors in HCC. Gene set enrichment analysis of the four FRGs showed statistically significant associations with pathways related to HCC proliferation. Finally, the TIMER and TISIDB databases indicated that the four FRGs were statistically significantly correlated with tumor-infiltrating immune cells and immune checkpoint expression. Taken together, this study provides information guiding a novel therapeutic strategy targeting FRGs for HCC treatment.

BRCA1/2 mutation is a biomarker for guiding multiple solid tumor treatment. However, the prevalence of BRCA1/2 large genomic rearrangements (LGRs) in Chinese cancer patients has not been well revealed partially due to technical difficulties in LGR detection. This study utilized next-generation sequencing (NGS) to analyze the BRCA1/2 mutation profile, including LGR, in 56126 Chinese cancer patients. We also reported that two ovarian and breast cancer patients with NGS-determined BRCA1/2 LGR benefited from PARP inhibitors (PARPi). DNA sequencing identified BRCA1/2 variants (including LGR, pathogenic and likely-pathogenic variants) in 2108 individuals. Seventy patients were discovered to harbor germline LGRs in BRCA1 and 14 had germline LGRs in BRCA2. Among the LGRs detected, exon 1-2 deletion was the predominant LGR (14/70) in BRCA1, and exon 22-24 deletion was the most frequent LGR (3/14) in BRCA2. Notably, the BRCA1 exon 7 deletion was a novel LGR and was identified in six patients, suggesting a specific LGR in Chinese cancer patients. The prevalence analysis of BRCA1 and BRCA2 LGRs across multiple cancers revealed that BRCA1 LGR more frequently occurred in ovarian cancer (1.31%, 33/2526), and BRCA2 LGR was more commonly seen in cholangiocarcinoma (0.47%, 2/425). Two ovarian and breast cancer patients with BRCA1/2 LGR benefited from PARPi therapy. This is the first study to reveal the BRCA1/2 LGR profile of a Chinese pan-cancer cohort by using an NGS-based assay. Two breast and ovarian cancer patients harboring NGS-determined BRCA1/2 LGR benefited from PARPi, indicating that NGS-based detection of BRCA1/2 LGR has the potential to guide PARPi treatment.

In China, the invasion of Spartina alterniflora is an important driver for the decrease of mangrove area and ecological service functions related to this habitat. In the past few decades, S. alterniflora clearing and mangrove restoration projects have mainly focused on the areas where it is already changed but ignored the potential distribution areas. This study suggested that implementation of mangrove protection prior to the areas with the threat of S. alterniflora invasion could greatly improve protection efficiency and save costs. Thus, using Maximum Entropy Modeling (MaxEnt), we estimated the potential spatial distribution of both mangroves and S. alterniflora in China, considering the current distribution data, topographical, sediments, sea surface temperature and bioclimatic variables. What’s more, we identified and calculated the potential distributed areas in each province. We aimed to explore (i) the key factors determining the distribution of mangrove and Spartina alterniflora along the coastline and (ii) the hotspots of their competitive occurrence, including S. alterniflora invasion areas and mangroves degradation areas, in order to support mangrove conservation. The model showed that the distance to the coastline and the topography play important roles in the distribution of S. alterniflora, while mangroves were more sensitive to the range of the annual sea surface temperature. Our results furthermore confirm that S. alterniflora has a wider potential distribution area (~10,585 km2) than mangroves (~9124 km2) at the coastline of China; and predict the provinces Zhangzhou, Quanzhou, Zhanjiang, Beihai and Wenzhou as hotspots for the competition between mangroves and S. alterniflora. We propose that priority should be given to the protection or restoration of mangrove plants in those areas which are co-suitable for mangroves and S. alterniflora. In these areas, management measures should be conducted that hinder S. alterniflora invasions or clear existing S. alterniflora plants, firstly. This study provides guidance for the management of native species by preventing biological invasion.

The cooling performance of nanoparticle (NP)-doped radiative cooling materials depends on the dispersion of the NPs in the polymer matrix. However, it is a technical challenge to suppress agglomeration of NPs due to their high surface energy, resulting in poor dispersion of the NPs in the polymer matrix. In order to optimize the dispersion of zinc oxide (ZnO) NPs in low-density polyethylene (LDPE), NPs were treated with atmospheric pressure plasmas for 30, 60 and 90 s. The ZnO NPs were dispersed in LDPE using a xylene solution method. The dispersion of the NPs was progressively improved as the plasma-treatment time increased, likely due to the roughened and perhaps also activated NP surfaces by the plasma treatment. This made the transmittances of the films decrease in the solar-radiation band and absorptivity increased monotonically in the high-energy band as the plasma-treatment time increased, while in the mid-infrared band, the films maintained a similar high transmittance to the untreated sample. The differential scanning colorimetry analysis revealed that the crystallinities of the plasma-treated NP-doped samples were similar to those of the untreated sample. The cooling-performance tests showed that the maximum temperature reductions of the films with NP plasma-treated for 0 s, 30 s, 60 s and 90 s were 6.82, 7.90, 9.34 and 10.34 °C, respectively, corresponded to the intrinsic temperature reductions of 7.27, 8.23, 10.54, and 11.40 °C, respectively, when calculated using Cui’s Model. The results of the current study show that a simple one-step atmospheric pressure plasma treatment to the ZnO NPs can indeed improve dispersion of the NPs in LDPE and lead to the greatly improved passive-cooling performance of the film.

Sea level rise (SLR) has a significant impact on the vegetation ecosystem in coastal wetlands. Taking coastal China as the study area, the SLAMM (sea level rise affecting marsh model) was used to simulate the continuous long-term (2015–2100) effects of the spatiotemporal changes in mangrove and Spartina alterniflora in the four shared socioeconomic pathway scenarios (SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5) of sea level rise by 2100; then, ArcGis was used to assess and compare the impact of SLR on land use. The results are as follows. (1) The dramatic reduction in the vegetation area is positively correlated with the rate of sea level rise. (2) Tidal differences and sedimentation rates affect the response of mangrove and S. alterniflora distribution to sea level rise, as well as interactions between organisms. (3) The reasonable land use of coastal wetlands is important to researchers. Land use is one of the tools for effective mangrove conservation. In conclusion, in scientific research and production practice, it is important to combine the biotic and abiotic factors affecting the distribution of mangroves and S. alterniflora.

We propose a DIDE-FPP composite algorithm to improve the spatial location accuracy of tunnel fires based on the distributed individuals differential evolution (DIDE) algorithm and the four-point positioning (FPP) method. Using the DIDE algorithm to solve the multimodal optimization problems in tunnel fire location can locate more peaks and improve peak finding, and the FPP method is used to process the peak points located using the DIDE and achieve the spatial location which cannot be achieved otherwise using the DIDE method only. We used 20 multimodal test functions to evaluate the performance of the DIDE-FPP algorithm in peak finding and solving MMOPs. Through experimental comparisons with 13 other existing advanced methods, the comprehensive performance of the proposed DIDE-FPP composite algorithm shows advantages to some extents. Additionally, the combined value of PR (peak ratio) and SR (success rate) on up to 20 experimental functions is relatively high. The spatial positioning accuracy of a tunnel fire warning system using this positioning method can reach the centimeter level.

Ulcers resulting from tophaceous gout are uncommon and very difficult to heal. Here we report a case with chronic refractory tophaceous gout, not responding to conventional treatment modality for several months in a 39-year-old man with a 12-year history of gout with recurrent acute arthritis attacks. Two times after treatment with autologous platelet-rich gel (APG), the ulcer healed finally for 2 months. This is the first study to confirm that APG can improve tophus ulcer healing. Based on conventional medical therapy and standard debridement, APG might be a novel and effective method to stimulate tophus ulcer healing.

Labile fractions of soil carbon pools are sensitive to environmental changes, which would influence the stabilization of soil carbon. However, it is unclear whether the dynamics of labile organic carbon (LOC) and soil organic carbon (SOC) are coupled and how they influence each other in coastal wetland. The present work investigated the trends of soil carbon fractions among mangrove and Spartina alterniflora communities with different stand ages (1, 5, 10, and 15 years), at Quanzhou Bay Estuary Wetland Nature Reserve, China. We found that SOC in a mangrove ecosystem increased over time, while there was no significant trend in S. alterniflora dominated ecosystems. The highest LOC of mangrove appeared in 5-year-old communities, and then decreased with stand age. In S. alterniflora communities, content of labile fractions increased with the stand age. These trends indicated different soil carbon dynamics when comparing mangrove and S. alterniflora ecosystems. The development of mangroves promoted accumulation of recalcitrant carbon, while S. alterniflora ecosystems contributed to an increase of labile carbon. This phenomenon is probably caused by the characteristics of vegetation and the hydrological conditions. Mangroves contribute more refractory organic carbon to the soil carbon pool, while accumulation of LOC in S. alterniflora communities may inhibit the stabilization of SOC. Our study on the relationship of LOC and SOC implies that complex interactions occur among soil carbon pools and environmental conditions in coastal wetlands, suggesting soil carbon models should take into account decoupled dynamics of LOC and SOC.

Long noncoding RNAs have been shown to play a role in cardiovascular disease. Here, the authors identify a lncRNA named CCRR, whose downregulation in failing hearts causes cardiac conduction disturbances by altering the endocytic trafficking of Cx43.

It has been reported that the invasion of Spartina alterniflora changed the soil microbial community in the mangrove ecosystem in China, especially the bacterial community, although the response of soil fungal communities and soil microbial ecological functions to the invasion of Spartina alterniflora remains unclear. In this study, we selected three different communities (i.e., Spartina alterniflora community (SC), Spartina alterniflora–mangrove mixed community (TC), and mangrove community (MC)) in the Zhangjiangkou Mangrove Nature Reserve in China. High-throughput sequencing technology was used to analyze the impact of Spartina alterniflora invasion on mangrove soil microbial communities. Our results indicate that the invasion of Spartina alterniflora does not cause significant changes in microbial diversity, but it can alter the community structure of soil bacteria. The results of the LEfSe (LDA Effect Size) analysis show that the relative abundance of some bacterial taxa is not significantly different between the MC and SC communities, but different changes have occurred during the invasion process (i.e., TC community). Different from the results of the bacterial community, the invasion of Spartina alterniflora only cause a significant increase in few fungal taxa during the invasion process, and these taxa are at some lower levels (such as family, genus, and species) and classified into the phylum Ascomycota. Although the invasion of Spartina alterniflora changes the taxa with certain ecological functions, it may not change the potential ecological functions of soil microorganisms (i.e., the potential metabolic pathways of bacteria, nutritional patterns, and fungal associations). In general, the invasion of Spartina alterniflora changes the community structure of soil microorganisms, but it may not affect the potential ecological functions of soil microorganisms.

BACKGROUND: Mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) have been studied for damaged liver repair; however, the conclusions drawn regarding their homing capacity to the injured liver are conflicting. Besides, the relative utility and synergistic effects of these two cell types on the injured liver remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: MSCs, HSCs and the combination of both cells were obtained from the bone marrow of male mice expressing enhanced green fluorescent protein(EGFP)and injected into the female mice with or without liver fibrosis. The distribution of the stem cells, survival rates, liver function, hepatocyte regeneration, growth factors and cytokines of the recipient mice were analyzed. We found that the liver content of the EGFP-donor cells was significantly higher in the MSCs group than in the HSCs or MSCs+HSCs group. The survival rate for the MSCs group was significantly higher than that of the HSCs or MSCs+HSCs group; all surpassed the control group. After MSC-transplantation, the injured livers were maximally restored, with less collagen than the controls. The fibrotic areas had decreased to a lesser extent in the mice transplanted with HSCs or MSCs+HSCs. Compared with mice in the HSCs group, the mice that received MSCs had better improved liver function. MSCs exhibited more remarkable paracrine effects and immunomodulatory properties on hepatic stellate cells and native hepatocytes in the treatment of the liver pathology. Synergistic actions of MSCs and HSCs were most likely not observed because the stem cells in liver were detected mostly as single cells, and single MSCs are insufficient to provide a beneficial niche for HSCs. CONCLUSIONS/SIGNIFICANCE: MSCs exhibited a greater homing capability for the injured liver and modulated fibrosis and inflammation more effectively than did HSCs. Synergistic effects of MSCs and HSCs were not observed in liver injury.

Despite the extensive hepatic differentiation potential of human umbilical cord lining-derived mesenchymal stem cells (hUC-MSC), little is known about the molecular mechanisms of hUC-MSC differentiation. At the post-transcriptional level, microRNAs are key players in the control of cell fate determination during differentiation. In this study, we aimed to identify microRNAs involved in the hepatic differentiation of hUC-MSCs. After successfully isolating hUC- MSCs, we induced hepatocyte formation in vitro with growth factors. After 26 days of induction, hUC-MSCs could express hepatocyte-specific genes, synthesize urea and glycogen and uptake low-density lipoprotein. Cellular total RNA from hUC-MSCs and hepatic differentiated hUC-MSCs was collected at 7 time points, including 2 days, 6 days, 10 days, 14 days, 22 days and 26 days, for microRNA microarray analysis. Dynamic microRNA profiles were identified that did not overlap or only partially overlapped with microRNAs reported to be involved in human liver development, hepatocyte regeneration or hepatic differentiation of liver-derived progenitor cells. A total of 61 microRNAs among 1205 human and 144 human viral microRNAs displayed consistent changes and were altered at least 2-fold between hUC-MSCs and hepatic differentiated hUC-MSCs. Among these microRNAs, 25 were over-expressed; this over-expression occurred either gradually or increased sharply and was maintained at a high level. A total of 36 microRNAs were under-expressed, with an expression pattern similar to that of the over-expressed microRNAs. The expression of the altered expressed microRNAs was also confirmed by quantitative reverse-transcription polymerase chain reaction. We also found that microRNAs involved in hepatic differentiation were not enriched in hepatocyte or hepatocellular carcinoma cells and can potentially target liver-enriched transcription factors and genes. The elucidation of the microRNA profile during the hepatic differentiation of hUC-MSCs provides the basis for clarifying the role of microRNAs in hUC-MSC hepatic differentiation and specific microRNA selection for the conversion of hUC-MSCs to hepatocytes.

Our previous study revealed that human ribosomal protein L6 (RPL6) was up-regulated in multidrug-resistant gastric cancer cells and over-expression of RPL6 could protect gastric cancer from drug-induced apoptosis. It was further demonstrated that up-regulation of RPL6 accelerated growth and enhanced in vitro colony forming ability of GES cells while down-regulation of RPL6 exhibited the opposite results. The present study was designed to investigate the potential role of RPL6 in therapy of gastric cancer for clinic. The expression of RPL6 and cyclin E in gastric cancer tissues and normal gastric mucosa was evaluated by immunohistochemisty. It was found that RPL6 and cyclin E were expressed at a higher level in gastric cancer tissues than that in normal gastric mucosa and the two were correlative in gastric cancer. Survival time of postoperative patients was analyzed by Kaplan- Meier analysis and it was found that patients with RPL6 positive expression showed shorter survival time than patients that with RPL6 negative expression. RPL6 was then genetically down-regulated in gastric cancer SGC7901 and AGS cell lines by siRNA. It was demonstrated that down-regulation of RPL6 reduced colony forming ability of gastric cancer cells in vitro and reduced cell growth in vivo. Moreover, down-regulation of RPL6 could suppress G1 to S phase transition in these cells. Further, we evidenced that RPL6 siRNA down-regulated cyclin E expression in SGC7901 and AGS cells. Taken together, these data suggested that RPL6 was over-expressed in human gastric tissues and caused poor prognosis. Down-regulation of RPL6 could suppress cell growth and cell cycle progression at least through down-regulating cyclin E and which might be used as a novel approach to gastric cancer therapy.