Male infertility is a major concern affecting human reproductive health. Asthenoteratospermia can cause male infertility through reduced motility and abnormal morphology of spermatozoa. Several ...genes, including DNAH1 and some CFAP family members, are involved in multiple morphological abnormalities of the sperm flagella (MMAF). However, these known genes only account for approximately 60% of human MMAF cases. Here, we conducted further genetic analyses by using whole-exome sequencing in a cohort of 65 Han Chinese men with MMAF. Intriguingly, bi-allelic mutations of TTC21A (tetratricopeptide repeat domain 21A) were identified in three (5%) unrelated, MMAF-affected men, including two with homozygous stop-gain mutations and one with compound heterozygous mutations of TTC21A. Notably, these men consistently presented with MMAF and additional abnormalities of sperm head-tail conjunction. Furthermore, a homozygous TTC21A splicing mutation was identified in two Tunisian cases from an independent MMAF cohort. TTC21A is preferentially expressed in the testis and encodes an intraflagellar transport (IFT)-associated protein that possesses several tetratricopeptide repeat domains that perform functions crucial for ciliary function. To further investigate the potential roles of TTC21A in spermatogenesis, we generated Ttc21a mutant mice by using CRISPR-Cas9 technology and revealed sperm structural defects of the flagella and the connecting piece. Our consistent observations across human populations and in the mouse model strongly support the notion that bi-allelic mutations in TTC21A can induce asthenoteratospermia with defects of the sperm flagella and head-tail conjunction.
In the author's institution, 2254 patients with hepatocellular carcinoma (HCC) have been treated during 1958-1994. The overall 5-year survival increased from 5.4% (1958-1970), to 11.9% (1971-1982), ...to 46.2% (1983-1984), which correlated well with the increasing proportion of small HCC in the series (2.6%, 12.1%, and 33.4%, respectively); with the increasing percentage of limited resection (3.1%, 32.2%, and 58.3%); with the increasing number of re-resections for recurrence (0, 27, and 114 patients); and with the increasing number of second stage resections (0, 5, and 67 patients). In our institution, surgical approaches that resulted in significantly prolonging survival included: small HCC resection, re-resection, and cytoreduction followed by sequential resection for initially unresectable HCC. Experience in these 3 aspects suggests: (a) Small HCCs are mainly found by screening using AFP and ultrasonography (US) in a high risk population, and limited resection is the best treatment in patients with compensated liver cirrhosis, the 5-year survival after resection being 62.9% (n = 549). (b) Postoperative monitoring using AFP/US every 2-3 months for 5-10 years after curative resection is needed to detect subclinical recurrence. Limited re-resection is indicated for liver recurrence less than 3 nodules, and lung lobectomy is of proven merit to prolong survival for solitary lung metastasis. Re-resection of subclinical recurrence has resulted in a 10-20% further increase in 5-year survival after curative resection. (c) Palliative surgery other than resection such as hepatic artery ligation (HAL) and cannulation with arterial infusion (HAI), cryosurgery, etc. are superior to palliative resection with residual cancer. (d) Cytoreduction and sequential resection have provided hope for localized unresectable HCC, particularly in the right cirrhotic liver. Multimodality combination treatments such as HAL+HAI+radioimmunotherapy/regional radiotherapy are acceptable cytoreductive therapies. Repeated transcatheter hepatic arterial chemoembolization (TACE) is an alternative nonsurgical approach. Sequential resection is important to eradicate residual cancer after cytoreduction. The 5-year survival of 72 patients with cytoreduction and sequential resection for initially unresectable HCC was 62.1% and resulted in improving 5-year survival in the entire series of unresectable HCC over the 3 periods from 0% to 7.4% to 25.7%, respectively. However, multicentric origin and tumor invasiveness are two major targets to be studied in the control of recurrence and metastasis.
Climate conditions significantly affect vegetation growth in terrestrial ecosystems. Due to the spatial heterogeneity of ecosystems, the vegetation responses to climate vary considerably with the ...diverse spatial patterns and the time‐lag effects, which are the most important mechanism of climate–vegetation interactive effects. Extensive studies focused on large‐scale vegetation–climate interactions use the simultaneous meteorological and vegetation indicators to develop models; however, the time‐lag effects are less considered, which tends to increase uncertainty. In this study, we aim to quantitatively determine the time‐lag effects of global vegetation responses to different climatic factors using the GIMMS3g NDVI time series and the CRU temperature, precipitation, and solar radiation datasets. First, this study analyzed the time‐lag effects of global vegetation responses to different climatic factors. Then, a multiple linear regression model and partial correlation model were established to statistically analyze the roles of different climatic factors on vegetation responses, from which the primary climate‐driving factors for different vegetation types were determined. The results showed that (i) both the time‐lag effects of the vegetation responses and the major climate‐driving factors that significantly affect vegetation growth varied significantly at the global scale, which was related to the diverse vegetation and climate characteristics; (ii) regarding the time‐lag effects, the climatic factors explained 64% variation of the global vegetation growth, which was 11% relatively higher than the model ignoring the time‐lag effects; (iii) for the area with a significant change trend (for the period 1982–2008) in the global GIMMS3g NDVI (P < 0.05), the primary driving factor was temperature; and (iv) at the regional scale, the variation in vegetation growth was also related to human activities and natural disturbances. Considering the time‐lag effects is quite important for better predicting and evaluating the vegetation dynamics under the background of global climate change.
Over the last two or three decades, the pace of development of treatments for osteosarcoma tends has been slow. Novel effective therapies for osteosarcoma are still lacking. Previously, we reported ...that tumor-suppressing STF cDNA 3 (TSSC3) functions as an imprinted tumor suppressor gene in osteosarcoma; however, the underlying mechanism by which TSSC3 suppresses the tumorigenesis and metastasis remain unclear.
We investigated the dynamic expression patterns of TSSC3 and autophagy-related proteins (autophagy related 5 (ATG5) and P62) in 33 human benign bone tumors and 58 osteosarcoma tissues using immunohistochemistry. We further investigated the correlations between TSSC3 and autophagy in osteosarcoma using western blotting and transmission electronic microscopy. CCK-8, Edu, and clone formation assays; wound healing and Transwell assays; PCR; immunohistochemistry; immunofluorescence; and western blotting were used to investigated the responses in TSSC3-overexpressing osteosarcoma cell lines, and in xenografts and metastasis in vivo models, with or without autophagy deficiency caused by chloroquine or ATG5 silencing.
We found that ATG5 expression correlated positively with TSSC3 expression in human osteosarcoma tissues. We demonstrated that TSSC3 was an independent prognostic marker for overall survival in osteosarcoma, and positive ATG5 expression associated with positive TSSC3 expression suggested a favorable prognosis for patients. Then, we showed that TSSC3 overexpression enhanced autophagy via inactivating the Src-mediated PI3K/Akt/mTOR pathway in osteosarcoma. Further results suggested autophagy contributed to TSSC3-induced suppression of tumorigenesis and metastasis in osteosarcoma in vitro and in vivo models.
Our findings highlighted, for the first time, the importance of autophagy as an underlying mechanism in TSSC3-induced antitumor effects in osteosarcoma. We also revealed that TSSC3-associated positive ATG5 expression might be a potential predictor of favorable prognosis in patients with osteosarcoma.
A scalable solution‐based approach is developed to controllably grow PPy ultrathin films on 2D MoS2 monolayers. When these sandwiched nanocomposites are utilized as supercapacitor electrodes, a ...record high specific capacitance, remarkable rate capability, and improved cycling stability are achieved, offering a feasible solution to create the next generation of energy‐storage device with superior power density and energy density.
Capacitive deionization (CDI) is an emerging technology for energy-efficient water desalination, and attracts more and more attention in recent years. It has been concluded that CDI technology shows ...competitiveness and perspectives on seawater desalination and wastewater treatment. The ionic adsorption mechanism can be clarified by electric double-layer capacitive adsorption and pseudocapacitive adsorption. The performance of CDI depends on both device and materials. The adsorption capacity and energy efficiency was improved significantly with fast growth of researches on material and novel energy storage techniques. This review summarizes researches on CDI technologies with an emphasis on electrode material design and improved adsorption performance.
This review outlines the ion storage mechanisms and electrode materials of capacitive deionization. Display omitted
•Electrochemical extraction of ions from seawater/brine was reviewed systematically.•An emphasis on electrode material design thought has been analyzed.•The performance of various extraction devices has been summarized and compared.•Future challenge on this technology has been clarified.
Conductive elastic composites have been used widely in soft electronics and soft robotics. These composites are typically a mixture of conductive fillers within elastomeric substrates. They can sense ...strain via changes in resistance resulting from separation of the fillers during elongation. Thus, most elastic composites exhibit a negative piezoconductive effect, i.e. the conductivity decreases under tensile strain. This property is undesirable for stretchable conductors since such composites may become less conductive during deformation. Here, we report a liquid metal-filled magnetorheological elastomer comprising a hybrid of fillers of liquid metal microdroplets and metallic magnetic microparticles. The composite's resistivity reaches a maximum value in the relaxed state and drops drastically under any deformation, indicating that the composite exhibits an unconventional positive piezoconductive effect. We further investigate the magnetic field-responsive thermal properties of the composite and demonstrate several proof-of-concept applications. This composite has prospective applications in sensors, stretchable conductors, and responsive thermal interfaces.
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