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e. myotendinous junctions and myofibrillar lesions; (iii) the number of lesions is greatly increased and these lesions lack Bcl2-associated athanogene 3 (BAG3) protein; (iv) the expression of heat shock protein beta-7 (HSPB7) is almost completely abolished. These findings indicate grave disturbances of BAG3-dependent and -independent autophagy pathways that are required for efficient lesion repair. In addition, our studies reveal general mechanisms of lesion formation and demonstrate that defective FLNc dimerization via its carboxy-terminal domain does not disturb assembly and basic function of myofibrils. An alternative, more amino-terminally located dimerization site might compensate for that loss. Since filamins function as stress sensors, our data further substantiate that FLNc is important for mechanosensing in the context of Z-disc stabilization and maintenance.

Previous studies have investigated the effects of anti-Müllerian hormone (AMH) and AMH type II receptor (AMHR2) polymorphisms on ovarian stimulation outcomes, but the results were inconsistent.

We searched PubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials databases for the literature used in this meta-analysis. The meta-analysis was performed with a random effects model with RevMan 5.3.5. Results were expressed as the relative risk (RR) for discrete data and the mean difference (MD) for continuous outcomes with a 95% confidence interval (CI).

Seven studies with 2078 participants were included. More metaphase II (MII) oocytes were retrieved in the T allele carrier of AMH (rs10407022) in the dominant model (MD 1.20, 95% CI 0.76 to 1.65, I

 = 0%, P < 0.00001), homozygote model (MD 1.68, 95% CI 0.35 to 3.01, I

 = 70%, P = 0.01) and heterogeneity model (MD 1.20, 95% CI 0.74 to 1.66, I

 = 0%, P < 0.00001). Oocytes retrieved from the Asian region in the TT carrier were significantly lesser than those in the GG/GT carrier in AMH (rs10407022) (MD -1.41, 95% CI - 1.75 to - 1.07, I

 = 0%). Differences in the stimulation duration, gonadotropin (Gn) dosage, and pregnancy rate were insignificant.

Our analysis indicated that the polymorphisms of AMH/AMHR2 could influence the ovarian stimulation outcomes. Prospective studies with a larger sample size and more rigorous design are needed in the future to further confirm these findings.

Our analysis indicated that the polymorphisms of AMH/AMHR2 could influence the ovarian stimulation outcomes. Prospective studies with a larger sample size and more rigorous design are needed in the future to further confirm these findings.

Cryptosporidium spp. are worldwide protozoan parasites which include species that can lead to cryptosporidiosis in humans. Different animal species can serve as reservoirs and sources of dissemination of the disease, such as rodent species due their potential in transmitting zoonotic pathogens to humans and other animals. In the Canary Islands (Spain), Cryptosporidium parvum and Cryptosporidium hominis have been identified in patients with diarrhea. However, the occurrence of Cryptosporidium spp. in possible reservoirs in this archipelago remains unclear. Considering the zoonotic potential of these protozoans, the aim of the present study was to determine the presence of Cryptosporidium spp. in peridomestic wild rodents and the possible role of these mammals as a source of transmission of these protozoans in Canary Islands.

A total of 179 rodents belonging to Rattus rattus and Mus musculus domesticus from four Canary Islands, La Palma, El Hierro, Tenerife and Lanzarote, were analyzed. Feces were screened ur study, future studies in non-sampled areas are required to better understand the epidemiology of these protozoans in wild rodents in the archipelago.

This study contributes to the knowledge of the biodiversity and distribution of Cryptosporidium spp. in wild rodents from the Canary Islands, highlighting the presence of three zoonotic species, C. tyzzeri, C. meleagridis and C. muris, being the first detection of these three species in wild rodents in the Canary Islands and the first report of C. meleagridis in R. rattus. Given the results obtained in our study, future studies in non-sampled areas are required to better understand the epidemiology of these protozoans in wild rodents in the archipelago.Osteosarcoma (OS) is the most common primary bone malignancy and responsible for considerable morbidity and mortality due to its high rates of pulmonary metastasis. Although neoadjuvant chemotherapy has improved 5-year survival rates for patients with localized OS from 20% to over 65%, outcomes for those with metastasis remain dismal. In addition, therapeutic regimens have not significantly improved patient outcomes over the past four decades, and metastases remains a primary cause of death and obstacle in curative therapy. These limitations in care have given rise to numerous works focused on mechanisms and novel targets of OS pathogenesis, including tumor niche factors. OS is notable for its hallmark production of rich extracellular matrix (ECM) of osteoid that goes beyond simple physiological growth support. The aberrant signaling and structural components of the ECM are rich promoters of OS development, and very recent works have shown the specific pathogenic phenotypes induced by these macromolecules. Here we summarize the current developments outlining how the ECM contributes to OS progression and metastasis with supporting mechanisms. We also illustrate the potential of tumorigenic ECM elements as prognostic biomarkers and therapeutic targets in the evolving clinical management of OS.

A role for the type II arginine methyltransferase PRMT5 in various human diseases has been identified. In this study, the potential mechanism underlying the involvement of PRMT5 in the pathological process leading to osteoarthritis (OA) was investigated.

PRMT5 expression in cartilage tissues from patients with OA and control individuals was assessed by immunohistochemical staining. The regulatory and functional roles of PRMT5 in the chondrocytes of patients with OA and control individuals were determined by western blotting and reverse transcription polymerase chain reaction. The effects of the PRMT5 inhibitor EPZ on interleukin-1β-induced inflammation were examined in the chondrocytes of patients with OA and in the destabilized medial meniscus (DMM) of a mouse model of OA.

PRMT5 was specifically upregulated in the cartilage of patients with OA. Moreover, adenovirus-mediated overexpression of PRMT5 in human chondrocytes caused cartilage degeneration. This degeneration was induced by elevated expression levels of matrix-degrading enzymes (matrix metalloproteinase-3 (MMP-3) and matrix metalloproteinase-13 (MMP-13)) in chondrocytes. The activation of the MAPK and nuclear factor κB signaling pathways was evidenced by elevated levels of p-p65, p-p38, and p-JNK. These effects were attenuated by inhibiting the expression of PRMT5. In the mouse model, EPZ inhibited PRMT5 expression, thus protecting mouse cartilage from DMM-induced OA.

Our results demonstrate that PRMT5 is a crucial regulator of OA pathogenesis, implying that EPZ has therapeutic value in the treatment of this cartilage-destroying disease.

Our results demonstrate that PRMT5 is a crucial regulator of OA pathogenesis, implying that EPZ has therapeutic value in the treatment of this cartilage-destroying disease.

Emerging evidence indicates nitrite inhalants have become increasingly prevalent among men who have sex with men (MSM). The present study aimed to describe the prevalence and correlates of nitrite inhalants use and its association with risky sexual behaviors and human immunodeficiency virus (HIV)/syphilis infection among MSM in Chongqing, a city in China where MSM were burdened with the highest pooled HIV prevalence in the country.

This cross-sectional study was conducted in Chongqing between March 2019 and February 2020. Information of demographics, drug use, sexual behaviors and HIV testing was collected through an anonymous survey. Blood samples were drawn from each participant for the diagnoses of HIV and syphilis. Logistic regression analysis was performed to evaluate factors correlated with nitrite inhalants use and its relationship with risky sexual behaviors and HIV/syphilis infection.

Of the 1151 eligible participants, 18.9% (218) reported use of at least one type of recreational drugs in the p past 6 months (aOR= 2.32, 95% CI 1.50-3.58), practicing CIE during anal sex in the past six months (aOR= 1.71, 95% CI 1.19-2.46), HIV infection (aOR= 1.72, 95% CI 1.11-2.66) and syphilis infection (aOR= 1.98, 95% CI 1.23-3.17).

This study found that nitrite inhalants were the most commonly used recreational substance among MSM and nitrite inhalants use were associated with higher probability of HIV and syphilis infection. Therefore, increased attention and counselling should be given to nitrite inhalants-using MSM.

This study found that nitrite inhalants were the most commonly used recreational substance among MSM and nitrite inhalants use were associated with higher probability of HIV and syphilis infection. Therefore, increased attention and counselling should be given to nitrite inhalants-using MSM.

Efforts to control and eliminate schistosomiasis have accelerated over the past decade. As parasite burden, associated morbidity and egg excretion decrease, diagnosis with standard parasitological methods becomes harder. We assessed the robustness and performance of a real-time PCR (qPCR) approach in comparison with urine filtration microscopy and reagent strip testing for the diagnosis of Schistosoma haematobium infections of different intensities.

The robustness of DNA isolation and qPCR was validated in eight laboratories from Europe and Africa. Subsequently, 792 urine samples collected during cross-sectional surveys of the Zanzibar Elimination of Schistosomiasis Transmission (ZEST) project in 2012-2017 were examined with qPCR in 2018. Diagnostic sensitivity of the qPCR was calculated at different infection intensity categories, using urine filtration microscopy as reference test. Spearman's rank correlation between Ct-values and S. haematobium egg counts was assessed and Ct-value percentiles for infece as many S. haematobium infections compared with classical parasitological tests. The qPCR is hence a sensitive, urine-based approach for S. haematobium diagnosis that can be used for impact assessment of schistosomiasis elimination programmes, individual diagnosis, and in improved format also for verification and certification of elimination.

ISRCTN, ISRCTN48837681 . Registered 05 September 2012 - Retrospectively registered.

ISRCTN, ISRCTN48837681 . Registered 05 September 2012 - Retrospectively registered.Non-coding RNAs (ncRNAs) have been the focus of many studies over the last few decades, and their fundamental roles in human diseases have been well established. Transfer RNAs (tRNAs) are housekeeping ncRNAs that deliver amino acids to ribosomes during protein biosynthesis. tRNA fragments (tRFs) are a novel class of small ncRNAs produced through enzymatic cleavage of tRNAs and have been shown to play key regulatory roles similar to microRNAs. MSAB mouse Development and application of high-throughput sequencing technologies has provided accumulating evidence of dysregulated tRFs in cancer. Aberrant expression of tRFs has been found to participate in cell proliferation, invasive metastasis, and progression in several human malignancies. These newly identified functional tRFs also have great potential as new biomarkers and therapeutic targets for cancer treatment. In this review, we focus on the major biological functions of tRFs including RNA silencing, translation regulation, and epigenetic regulation; summarize recent research on the roles of tRFs in different types of cancer; and discuss the potential of using tRFs as clinical biomarkers for cancer diagnosis and prognosis and as therapeutic targets for cancer treatment.