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Background: Highly heterogeneity and inconsistency in terms of prognosis are widely identified for early‐stage cervical cancer (esCC). Herein, we aim to investigate for an intuitional risk stratification model for better prognostication and decision‐making in combination with clinical and pathological variables. Methods: We enrolled 2071 CC patients with preoperative biopsy‐confirmed and clinically diagnosed with FIGO stage IA‐IIA who received radical hysterectomy from 2013 to 2018. Patients were randomly assigned to the training set (n = 1450) and internal validation set (n = 621), in a ratio of 7:3. We used recursive partitioning analysis (RPA) to develop a risk stratification model and assessed the ability of discrimination and calibration of the RPA‐derived model. The performances of the model were compared with the conventional FIGO 2018 and 9th edition T or N stage classifications. Results: RPA divided patients into four risk groups with distinct survival: 5‐year OS for RPA I to IV were 98%, 95%, 85.5%, and 64.2%, respectively, in training cohort; and 99.5%, 93.2%, 85%, and 68.3% in internal validation cohort (log‐rank p < 0.001). Calibration curves confirmed that the RPA‐predicted survivals were in good agreement with the actual survivals. The RPA model outperformed the existing staging systems, with highest AUC for OS (training: 0.778 vs. 0.6–0.717; internal validation: 0.772 vs. 0.595–0.704; all p < 0.05), and C‐index for OS (training: 0.768 vs. 0.598–0.707; internal validation: 0.741 vs. 0.583–0.676; all p < 0.05). Importantly, there were associations between RPA groups and the efficacy of treatment regimens. No obvious discrepancy was observed among different treatment modalities in RPA I (p = 0.922), whereas significant survival improvements were identified in patients who received adjuvant chemoradiotherapy in RPA II–IV (p value were 0.028, 0.036, and 0.024, respectively). Conclusion: We presented a validated novel clinicopathological risk stratification signature for robust prognostication of esCC, which may be used for streamlining treatment strategies. [ABSTRACT FROM AUTHOR]

ERA5 reanalysis data, precipitation data from China, and National Oceanic and Atmospheric Administration (NOAA) monthly sea surface temperature (SST) data are used to analyse the impact of the meridional position of the East Asian subtropical jet (EASJ) on summer precipitation in China and its correlation with Atlantic SST. The results indicate that when the EASJ significantly shifts northward, the western North Pacific subtropical high (WNPSH) weakens with an eastward displacement. Upper‐level convergence and moisture divergence, corresponding to descending motion, lead to decreased precipitation in the Yangtze River Valley (YRV). Meanwhile, upper‐level divergence occurs over South China (SC), the Hexi Corridor (HC), and Northeast China (NEC), where moisture converges and ascends, favouring an increase in precipitation. Conversely, when the EASJ undergoes a significant southward shift, the WNPSH strengthens and expands westward. Opposing atmospheric circulation patterns in these four regions result in reversed precipitation anomalies compared with those observed when the jet shifts northward. The meridional position of the EASJ is closely related to the summer subtropical Atlantic SST. The positive (negative) SST anomaly (SSTA) over the subtropical Atlantic induces negative (positive) geopotential height anomaly in the upper troposphere over the North Atlantic by modulating the atmospheric meridional circulation. Geopotential height anomalies trigger eastward‐propagating Rossby waves, generating anomalous cyclones and anticyclones over East Asia. These anomalous cyclones and anticyclones lead to zonal wind anomalies, which alter the strength of the westerlies on both sides of the climatological jet axis, thereby changing the jet's meridional position. Additionally, the difference in the propagation direction of wave activity flux between positive and negative SSTA alters the distribution of wave energy convergence and divergence in the EASJ region, further affecting the intensity of the average westerly winds on both sides of the climatological jet axis, ultimately producing the changes in the meridional position of the EASJ. [ABSTRACT FROM AUTHOR]

Oyster peptide (OP) and Pfaffia glomerata extract (PGE) were used as raw materials. The optimal formulation of the pressed candy (PC) was optimized by one‐way experiment and D‐optimal mixture experiment design, and animal experiment was used to evaluate the effect of PC on male sexual dysfunction. The results showed that PC intervention significantly improved the sexual behavior of male mice with sexual dysfunction, including a significant shortening of the mount latency (ML) and intromission latency, and a significant increase in the mount frequency (MF) and intromission frequency (IF). At the same time, the concentrations of serum testosterone (T) and luteinizing hormone (LH) in mice were restored, and the erectile parameters and pathological changes of penile tissue were improved. Further studies found that PC intervention increased the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH‐Px) and reduced the content of malondialdehyde (MDA) in testicular tissue. In addition, PC intervention improved testicular tissue morphology. In conclusion, the obtained PC has good taste quality, and the relevant quality indicators are qualified. It has a good ameliorative effect on male sexual dysfunction and may be a potential dietary supplement. [ABSTRACT FROM AUTHOR]

Aim: Previous studies have indicated that early metastasis is a major cause of mortality in patients with choriocarcinoma. However, what determines whether early metastasis of choriocarcinoma has occurred is unknown. The emerging role of miRNA in regulating cancer development and progression has been recognized. miR‐373 has been shown to play pivotal roles in tumorigenesis and metastasis. However, whether miR‐373 functions to promote choriocarcinoma metastasis is not clear. The purpose of this study is to determine the function of miR‐373‐3p in the progression of this cancer. Methods: In this study, we first compared epithelial–mesenchymal transition (EMT)‐related markers, which were inversely correlated with miR‐373‐3p expression in trophoblast and choriocarcinoma cell lines. Using PCR and Western blot, upregulation of miR‐373‐3p was observed to inhibit EMT progression. Similarly, gain‐ and loss‐of‐function studies revealed that ectopic miR‐373‐3p overexpression inhibited the migration by transwell methods of choriocarcinoma cells. Results: Our results revealed that miR‐373‐3p acted as an EMT inhibitor in JEG‐3 and JAR cells; this was due to its mediation of the transforming growth factor‐β (TGFβ) signaling pathway, which was responsible for EMT. miRNA microarray analysis demonstrated that miR‐373‐3p interacted with the 3′ untranslated region of TGFβR2 mRNA, and then Western blot and dual‐luciferase reporter gene assays verified this interaction. Conclusion: Our findings suggest that miR‐373‐3p upregulation partly accounts for TGFβR2 downregulation and leads to a restraint of EMT and migration. miR‐373‐3p may therefore serve as a valuable potential target in the treatment of choriocarcinoma. [ABSTRACT FROM AUTHOR]

BACKGROUND: Penicillic acid (PA) is produced by Aspergillus spp. and Penicillium spp., which are common postharvest and storage fungi of fruits. PA can be of concern for human health because of its toxicity and high fruit consumption by the population. However, no data on PA occurrence in various fruits have yet been reported. A quick, easy, cheap, effective, rugged and safe (QuEChERS) approach for PA determination in various fruits was developed and applied to explore PA incidence in fruits. RESULTS: The modified QuEChERS procedure with extraction by ethyl acetate and purification by multi‐walled carbon nanotubes (MWCNTs), primary secondary amine (PSA) and octadecyl silane (C18) was established to determine PA in various fruits by high‐performance liquid chromatography–tandem mass spectrometry (HPLC‐MS/MS). The average recoveries were 72.9–102.2% and relative standard deviations (RSDs) were 1.3–7.9%. A total of 161 fruits samples, including kiwi, apple, peach, grape and mandarin/orange, were collected in southern China. The incidence of PA in fruits was 14.9% and the levels of PA contamination were 0.200–0.596 μg kg−1. Our results suggested that orange/mandarin, grape and kiwi were favorable matrices for Aspergillus spp. and Penicillium spp. to produce PA, rather than peach and apple. CONCLUSION: To the best of our knowledge, this is the first report about PA contamination in various fruits in China. Our study emphasizes the necessity of the current established method, which could be used for continuous monitoring of PA and reducing the health risk to Chinese consumers. © 2020 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Osteogenesis imperfecta (OI) is a rare heritable disease with systemic connective tissue disorder. Most of the patients represent autosomal dominant form of OI, and are usually resulting from the mutations in type I collagen genes. However, the gene mutations reported previously only account for ∼70% of the OI cases. Here, in a Chinese OI family, we examined seven patients and nine normal individuals using the whole genome sequencing and molecular genetic analysis. The mutation of rs66612022 (COL1A2:p.Gly328Ser) related to glycine substitution was found in the seven patients. Moreover, we identified a novel missense mutation (HMMR:p.Glu2Gln). Interestingly, the individuals of this family with both the mutations were suffering from OI, while the others carried one or none of them are normal. The mutations of COL1A2 and HMMR and their combined effect on OI would further expand the genetic spectrum of OI. [ABSTRACT FROM AUTHOR]

Genetics might play various roles in susceptibility to recurrent miscarriage, and previous studies suggest that some gene polymorphisms might be associated with abortion and breast cancer onset. Colon cancer‐associated transcript 2 (CCAT2) is a novel long noncoding RNA (lncRNA) transcript that might be correlated with susceptibility to multiple cancers, including breast cancer. However, whether lncRNA CCAT2 polymorphisms are related to susceptibility to recurrent miscarriage is unclear. We genotyped two lncRNA CCAT2 polymorphisms (rs6983267 and rs3843549) in 248 patients with recurrent miscarriage and 392 controls through a TaqMan real‐time polymerase chain reaction assay, and the strength of each association was evaluated via 95% confidence intervals (CIs) and odds ratios (ORs). Our results showed that the rs6983267 G allele in lncRNA CCAT2 was associated with decreased susceptibility to recurrent miscarriage (TG vs. TT: adjusted OR = 0.603; 95% CI = 0.420–0.866; p = 0.0062; GG/TG vs. TT: adjusted OR = 0.620; 95% CI = 0.441–0.873; p = 0.0061). The combined analysis of the two protective polymorphisms (rs3843549 AA and rs6983267 TG/GG) revealed that individuals with two unfavorable alleles exhibited a lower risk of recurrent miscarriage than those with no or only one unfavorable allele (adjusted OR = 0.531; 95% CI = 0.382–0.739). Moreover, the decreased risk associated with the two protective alleles was most obvious in women aged less than 35 years (OR = 0.551; 95% CI = 0.378–0.8803; p = 0.0019) and in women with two to three miscarriages (adjusted OR = 0.466; 95% CI = 0.318–0.683; p < 0.0001). In conclusion, our study indicates that the rs6983267G allele might contribute to a decreased risk of recurrent miscarriage in the South Chinese population. [ABSTRACT FROM AUTHOR]

Background. Central precocious puberty (CPP) is defined by gonadotropin-dependent development of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys. MKRN3 and DLK1 are two genes, disease-causing variants of which have recently been discovered to cause idiopathic CPP. Methods. We screened 173 Chinese patients (9 males and 164 females; 9 familial and 164 sporadic) with ICPP and 43 patients (9 males and 34 females; 3 familial and 40 sporadic) with early puberty for variants in MKRN3. We also screened 19 patients with ICPP and early puberty for variants of DLK1 (17 males and 2 females; 5 familial and 14 sporadic). Results. We identified four novel missense variants of MKRN3, c.1138G > A (p.Glu380Lys), c.1420T > A (p.Leu474Met), c.673C > G (p.Leu225Val), and c.1071C > G (p.Ile357Met) in two sporadic cases and three familial cases. According to ACMG standards, two MKRN3 variant (p.Glu380Lys and p.Ile357Met) are likely pathogenic, and two others are of uncertain significance. We also performed bioinformatic analysis to evaluate the impact of variants on MKRN3 protein structures, which showed that Ile357Met locates at the zinc-binding region (C3HC4 RING finger motif), while Glu380Lys is spatially extremely close to the C3HC4 RING finger, MKRN-specific Cys-His domain, and the third C3H1 zinc-finger motif region. Per Glu380Lys, Glu with negative charges has been changed into Lys with positive charges, which may affect the hydrogen bond formation between amino acids and the stability of the local structure, thus affecting the binding of zinc iron to MKRN3 protein. Besides, we did not identify any variants of DLK1 gene in our patients. Conclusions. In this study, we report four novel MKRN3 variants in patients with ICPP. Moreover, we did not find any variants of DLK1 gene. Variants of MKRN3 are relatively uncommon in Chinese ICPP patients. [ABSTRACT FROM AUTHOR]

The maturity group (MG) system is widely used to group soybean [Glycine max (L.) Merr.] varieties based on their growth periods and photothermal responses. However, there is still no universal standard or quantifiable methodology for MG classification. In this study, phenological traits of 107 Chinese, 4 Far East Russian representative soybean varieties, and 113 North American reference varieties covering 13 MGs were evaluated at eight locations (ranging from 30 to 50° N) in four ecoregions of China for two consecutive years (2014 and 2015). Relative maturity groups (RMGs) were attributed to all the varieties based on the linear regression models. To decimalize the RMG values of the early‐maturing varieties belonging to MGs below 0, negative values were defined for MGs 00, 000, and 0000. The additive main effects and multiplicative interaction (AMMI) model was used to screen 185 standard candidate varieties for MGs 0000 to VIII. This study provided a systematic and quantifiable methodology for RMG identification in soybeans. The methodology is expected to be widely adopted by soybean regionalization and germplasm exchanges throughout the world and will be helpful for characterizing the photothermal sensitivity and adaptability of the given soybean varieties. [ABSTRACT FROM AUTHOR]

Background. Bone mineral density quantitative trait locus 18 (BMND18, OMIM #300910) is a type of early-onset osteogenesis imperfecta (OI) caused by loss-of-function mutations in the PLS3 gene, which encodes plastin-3, a key protein in the formation of actin bundles throughout the cytoskeleton. Here, we report a patient with PLS3 mutation caused BMND18 and evaluated all the reported disease-causing mutations by bioinformatic analysis. Methods. Targeted gene sequencing was performed to find the disease-causing mutation in our patient. Bioinformatic analyses mainly including homology modelling and molecular dynamics stimulation were conducted to explore the impact of the previously reported mutations on plastin-3. Results. Gene sequencing showed a novel nonsense mutation (c.745G > T, p.E249X), which locates at a highly conserved region containing residues p.240–266 (LOOP-1) in the PLS3 gene. Further bioinformatic analyses of the previously reported mutations revealed that LOOP-1 is predicted to physically connect the calponin-homology 1 (CH1) and CH2 domains of the ABD1 fragment and spatially locates within the interface of ABD1 and ABD2. It is crucial to the conformation transition and actin-binding function of plastin-3. Conclusions. This report identified a novel mutation that truncates the PLS3 gene. Moreover, bioinformatic analyses of the previous reported mutations in PLS3 gene lead us to find a critical LOOP-1 region of plastin-3 mutations at which may be detrimental to the integral conformation of plastin-3 and thus affect its binding to actin filament. [ABSTRACT FROM AUTHOR]

Background. Gonadal injury following chemotherapy is of increasing importance with the continuous improvement of survival rates. The protection of gonadotropin hormone antagonist (GnRHant) in long-term adult survivors of adolescent cancers and some autoimmune diseases has not yet been evaluated. Methods. The present study was aimed at longitudinally exploring whether the GnRHant could alleviate testicular damage induced by cyclophosphamide (CPA) in a rat model. Pubertal male rats were assigned to receive CPA with and without GnRHant. CPA was administrated at a single dose (100 mg/kg). GnRHant was started one hour prior to CPA injection and continued for four weeks (0.1 mg/kg, 3 times a week). Body and testes weights, testicular hormones, histological changes, and expression of androgen receptor (AR) in the testis were analyzed when rats matured into adulthood and completed a round of spermatogenesis. Results. Our results showed that body weight, histological injury, and AR expression in the testis were improved in the GnRHant + CPA group. However, testes weight and testicular hormones (anti-Müllerian hormone, inhibin B, and testosterone) did not markedly change. Conclusion. Our results indicate that the GnRHant administration before and after CPA in pubertal rats can protect long-term testicular injury induced by CPA via increased AR expression in the testes. [ABSTRACT FROM AUTHOR]