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Genetic improvement of grain yield is always an important objective in wheat breeding. Here, a genome-wide association study was conducted to parse the complex genetic composition of yield-related traits of 105 elite wheat varieties (lines) using the Wheat 90K Illumina iSelect SNP array. Nine yield-related traits, including maximum number of shoots per square meter (MSN), effective number of spikes per square meter (ESN), percentage of effective spike (PES), number of kernels per spike (KPS), thousand-kernel weight (TKW), the ratio of kernel length/kernel width (RLW), leaf-area index (LAI), plant height (PH), and grain yield (GY), were evaluated across four environments. Twenty four highly significant marker-trait associations (MTAs) (P < 0.001) were identified for nine yield-related traits on chromosomes 1A, 1D, 2A (2), 3B, 4A (2), 4B, 5A (4), 5B (4), 5D, 6B (2), 7A (2), and 7B (3), explaining 10.86-20.27% of the phenotypic variations. Of these, four major loci were identified in more than three environments, including one locus for RLW (6B), one locus for TKW (7A), and two loci for PH (7B). A cleaved amplified polymorphic sequence (CAPS) marker Td99211 for TKW on chromosome 5A was developed and validated in both a natural population composed of 372 wheat varieties (lines) and a RIL population derived from the cross of Yangxiaomai × Zhongyou 9507. The CAPS marker developed can be directly used for marker-assisted selection in wheat breeding, and the major MTAs identified can provide useful information for fine-mapping of the target genes in future studies.

Opisthopappus is a major wild source of Asteraceae with resistance to cold and drought. Two species of this genus ( Opisthopappus taihangensis and O. longilobus ) have been employed as model systems to address the evolutionary history of perennial herb biomes in the Taihang Mountains of China. However, further studies on the adaptive divergence processes of these two species are currently impeded by the lack of genomic resources. To elucidate the molecular mechanisms involved, a comparative analysis of these two species was conducted. Among the identified transcription factors, the bHLH members were most prevalent, which exhibited significantly different expression levels in the terpenoid metabolic pathway. O. longilobus showed higher level of expression than did O. taihangensis in terms of terpenes biosynthesis and metabolism, particularly monoterpenoids and diterpenoids. Analyses of the positive selection genes (PSGs) identified from O. taihangensis and O. longilobus revealed that 1203 genes were related to adaptative divergence, which were under rapid evolution and/or have signs of positive selection. Differential expressions of PSG occurred primarily in the mitochondrial electron transport, starch degradation, secondary metabolism, as well as nucleotide synthesis and S-metabolism pathway processes. Several PSGs were obviously differentially expressed in terpenes biosynthesis that might result in the fragrances divergence between O. longilobus and O. taihangensis , which would provide insights into adaptation of the two species to different environments that characterized by sub-humid warm temperate and temperate continental monsoon climates. The comparative analysis for these two species in Opisthopappus not only revealed how the divergence occurred from molecular perspective, but also provided novel insights into how differential adaptations occurred in Taihang Mountains.

In rice, the TGW6 gene determines grain weight and encodes a protein with indole-3-acetic acid (IAA)-glucose hydrolase activity. Its homolog in wheat, TaTGW6, is considered as a candidate gene related to grain development. To amplify this gene, we designed primers based on a homologous conserved domain of the rice TGW6 gene. Sequence analysis indicated that TaTGW6 comprises only one exon, with 1656 bp in total and an open reading frame of 1035 bp. Three alleles at TaTGW6 locus detected by the primer pair TG23 were designated as TaTGW6-a, TaTGW6-b and TaTGW6-c, respectively. Compared with TaTGW6-a, TaTGW6-b had a 6-bp InDel at the position 170 downstream of initiation codon, and TaTGW6-c was a null mutant. Both TaTGW6-b and TaTGW6-c could significantly increase grain size and weight other than TaTGW6-a; however, the former two alleles showed a low frequency distribution in modern varieties. TaTGW6 was located on chromosome 4AL using a recombinant inbred line population and a set of Chinese Spring nullisomic-tetrasomic lines. It was linked to the SSR locus Xbarc1047 with a genetic distance of 6.62 cM and explained 15.8–21.0 % of phenotypic variation of grain weight in four environments. Association analysis using a natural population and Chinese wheat mini-core collections additionally validated the relationship of TaTGW6 with grain weight; the gene could explain 7.7–12.4 % of phenotypic variation in three environments. Quantitative real-time PCR revealed that TaTGW6-b showed relatively lower expression than TaTGW6-a in immature grain at 20 and 30 days post-anthesis and in mature grain. The low expression of TaTGW6 generally associated with low IAA content, but with high grain weight. The novel functional marker, designated as TG23, can be used for marker-assisted selection to improve grain weight in wheat and also provides insights into the regulatory mechanism underlying grain weight.

Endometriosis is a chronic, estrogen-dependent condition associated with substantial physical and psychological burden. Although psychiatric comorbidities are frequently reported, large-scale real-world data remain limited. We conducted a retrospective cohort study using the TriNetX U.S. Collaborative Network, including women aged 21–60 diagnosed with endometriosis between 2001 and 2020. Patients were matched 1:1 with controls without endometriosis using propensity score matching (PSM) based on age, race, nicotine dependence, alcohol abuse, obesity, infertility, delivery history, insomnia, and menopause. Psychiatric outcomes included depressive episodes, recurrent major depressive disorder, anxiety disorders, and substance use disorders. Subgroup analyses assessed differences by race, age, and postoperative hormonal therapy use. After PSM, each group included 7563 patients. Endometriosis was significantly associated with increased risks of several psychiatric disorders, including depressive episodes (HR = 1.35, 95 % CI: 1.24–1.47), recurrent major depressive disorder (HR = 1.30, 95 % CI: 1.10–1.53), anxiety disorders (HR = 1.39, 95 % CI: 1.29–1.49), phobic anxiety disorder (HR = 1.47, 95 % CI: 1.01–2.13), and substance use disorders (HR = 1.43, 95 % CI: 1.30–1.56). The composite outcome of all assessed psychiatric disorders—including depressive episodes, recurrent major depressive disorder, anxiety disorders, phobic anxiety disorder, mental and behavioral disorders due to psychoactive substance use, and suicidal ideation—was also significantly elevated in the endometriosis group (HR = 1.38, 95 % CI: 1.30–1.46). These associations were most pronounced among White patients, while Black patients showed elevated risks for recurrent depression and anxiety disorders only. No significant associations were observed among Asian patients. Additionally, postoperative hormonal therapy did not significantly reduce the risk of psychiatric disorders compared to surgery alone. Women with endometriosis face elevated risks of psychiatric disorders, with notable racial disparities. Hormonal therapy may not mitigate these mental health risks. Our findings underscore the importance of integrated gynecologic and psychological care in the management of endometriosis. •Endometriosis increases risk of depression, anxiety, and substance use.•Psychiatric risks vary by race, with White patients most affected.•Hormonal therapy after surgery shows no protection against mental disorders.

Background Climate oscillation may have a profound effect on species distributions, gene flow patterns and population demography. In response to environmental change, those species restricted to montane habitats experienced expansions and contractions along elevation gradients, which can drive differentiation among sky islands. Results The Shangcheng stout salamander ( Pachyhynobius shangchengensis ) is a cool stream amphibian restricted to high-elevation areas in the Dabie Mountains, East China. In the present study, we used mtDNA genes (Cyt b and ND2 ) of 193 individuals and 12 nuclear microsatellite loci genotyped on 370 individuals, representing 6 populations (JTX, KHJ, MW, TTZ, BYM and KJY) across the taxon’s distribution area, to investigate their genetic variation and evolutionary history of P. shangchengensis . Most populations showed unusually high levels of genetic diversity. Phylogenetic analyses revealed five monophyletic clades with divergence times ranging from 3.96 to 1.4 Mya. Accordingly, significant genetic differentiation was present between these populations. Bayesian skyline plot analyses provided that all populations underwent long-term population expansions since the last inter-glacial (0.13 Mya ~ 0.12 Mya). Msvar analyses found recent signals of population decline for two northern populations (JTX and KHJ) reflecting a strong bottleneck (approximately 15-fold decrease) during the mid-Holocene (about 6000 years ago). Ecological niche modelling has shown a discontinuity in suitable habitats for P. shangchengensis under different historical climatic conditions. Conclusions Our results suggest that the niche conservatism of P. shangchengensis and sky island effects may have led to long-term isolation between populations. In sky island refuges, the mid-latitude Dabie Mountains have provided a long-term stable environment for P. shangchengensis , which has led to the accumulation of genetic diversity and has promoted genetic divergence.

Thousand-grain weight (TGW) of wheat ( L.) contributes significantly to grain yield. In the present study, a candidate gene associated with TGW was identified through specific-locus amplified fragment sequencing (SLAF-seq) of DNA bulks of recombinant inbred lines (RIL) derived from the cross between Jing 411 and Hongmangchun 21. The gene was located on chromosome 7A, designated as with a complete genome sequence and an open reading frame (ORF). A single nucleotide polymorphism (SNP) was present in the first exon between two alleles at locus, resulting in a Val to Ala substitution, corresponding to a change from higher to lower TGW. Cleaved amplified polymorphic sequence (CAPS) ( ) and InDel ( ) markers were developed to discriminate the two alleles and for higher and lower TGW, respectively. A major QTL co-segregating with explained 21.7-27.1% of phenotypic variance for TGW in the RIL population across five environments. The association of with TGW was further validated in a natural population and Chinese mini-core collections. Quantitative real-time PCR revealed higher transcript levels of than those of during grain development. High frequencies of the superior allele for higher TGW in Chinese mini-core collections (65.0%) and 501 wheat varieties (86.0%) indicated a strong and positive selection of this allele in wheat breeding. The molecular markers and can be used for improvement of TGW in breeding programs.

Background Uterine serous carcinoma and carcinosarcoma are aggressive forms of endometrial cancer with poor survival outcomes. Trastuzumab, a human epidermal growth factor receptor-2 (HER2)-directed monoclonal antibody, has demonstrated tumoricidal efficacy. However, clinical data regarding its efficacy in uterine serous carcinoma are limited, and there are no clinical data available for uterine carcinosarcoma. Therefore, this study aimed to ascertain the efficacy and safety of adding trastuzumab to carboplatin and paclitaxel as a frontline treatment for advanced-stage HER2-overexpressing uterine serous carcinoma and carcinosarcoma. Methods This retrospective study used deidentified data from electronic health records from the TriNetX Research Network. Participants were identified using International Classification of Diseases codes, and HER2 positivity was confirmed through immunohistochemistry or fluorescence in situ hybridisation. Propensity score matching was employed to reduce confounders, and survival outcomes and adverse events were assessed. Results Following propensity score matching, 280 patients with advanced HER2-positive uterine serous carcinoma or carcinosarcoma were analysed. The group of patients treated with carboplatin/paclitaxel + trastuzumab (CP + T) showed a significantly prolonged median overall survival compared to those treated exclusively with CP (41 months versus 25.2 months, hazard ratio [HR] = 0.51, p  = 0.002) in both advanced-stage uterine carcinosarcoma and serous carcinoma. Specifically, patients with uterine carcinosarcoma experienced a prolonged survival benefit (HR = 0.39, p  < 0.0001) when trastuzumab was added to their chemotherapy regimen, which surpassed the survival benefit observed in patients with uterine serous carcinoma (HR = 0.56, p  = 0.04). However, patients who received trastuzumab experienced increased rates of hypertension, diarrhoea, and left ventricular systolic dysfunction. Conclusions The addition of trastuzumab to frontline chemotherapy is effective in treating HER2-overexpressing uterine serous carcinoma and carcinosarcoma, particularly uterine carcinosarcoma. However, careful monitoring of adverse cardiac events is needed.

Treatment of bulky cervical cancer is associated with both high adverse effects and local recurrence rates with traditional box method radiotherapy. Intensity-modulated radiotherapy (IMRT) has been adopted for the treatment of cervical cancer in order to deliver more precise radiation doses to the target region. We retrospectively enrolled a total of 98 patients with cervical cancer ≥4 cm who completed IMRT and point A-based brachytherapy treatment. The median follow-up time of the cohort was 6.84 years, with the 5-year OS and DFS being 66.33% and 75.12%, respectively. In addition, 7.14% of patients experienced local recurrence, 12.24% had distant recurrence, 6.12% had both local and distant recurrence, and 3.06% had persistent disease. In the univariate analysis, lymph node metastasis, higher creatinine levels, higher initial CA-125 and receiving chemotherapy other than cisplatin were all associated with a worse PFS. A tumor size ≥6 cm was associated with an increased incidence of higher grade of acute diarrhea. Grade 3 late radiation proctitis and cystitis developed in 11.22% and 13.27% of patients, respectively. The local recurrence rates and overall efficiencies were not inferior to other studies involving traditional pelvic external beam radiation therapy with concurrent chemotherapy. The safety and efficacy of IMRT for bulky cervical cancer were acceptable.

To investigate the pattern of chloroplast genome variation in Triticeae, we comprehensively analyzed the indels in protein-coding genes and intergenic sequence, gene loss/pseudonization, intron variation, expansion/contraction in inverted repeat regions, and the relationship between sequence characteristics and chloroplast genome size in 34 monogenomic Triticeae plants. Ancestral genome reconstruction suggests that major length variations occurred in four-stem branches of monogenomic Triticeae followed by independent changes in each genus. It was shown that the chloroplast genome sizes of monogenomic Triticeae were highly variable. The chloroplast genome of Pseudoroegneria , Dasypyrum , Lophopyrum , Thinopyrum , Eremopyrum , Agropyron , Australopyrum , and Henradia in Triticeae had evolved toward size reduction largely because of pseudogenes elimination events and length deletion fragments in intergenic. The Aegilops / Triticum complex, Taeniatherum , Secale , Crithopsis , Herteranthelium , and Hordeum in Triticeae had a larger chloroplast genome size. The large size variation in major lineages and their subclades are most likely consequences of adaptive processes since these variations were significantly correlated with divergence time and historical climatic changes. We also found that several intergenic regions, such as pet N– trn C and psb E– pet L containing unique genetic information, which can be used as important tools to identify the maternal relationship among Triticeae species. Our results contribute to the novel knowledge of plastid genome evolution in Triticeae.

Background Lenvatinib plus pembrolizumab has demonstrated improved survival compared with doxorubicin or paclitaxel monotherapy in patients with advanced or recurrent endometrial cancers (ECs). However, response rates to monotherapy are poor in recurrent settings. Herein, we performed a retrospective analysis using real-world data to compare the outcomes of lenvatinib plus pembrolizumab, carboplatin plus paclitaxel (PT), and doxorubicin for patients with PT-pretreated, advanced, or recurrent ECs. Methods We performed a multi-institutional retrospective analysis using de-identified electronic health record database (TriNetX) to compare lenvatinib plus pembrolizumab, carboplatin plus paclitaxel (PT), and doxorubicin outcomes in patients with PT-pretreated, advanced, or recurrent ECs. A 1:1 propensity score matching (PSM) was conducted. The primary outcome was the overall survival (OS) among treatment groups. The secondary outcome was the adverse event profile. Results Between January 2012 and September 2023, we identified 397 patients with PT-treated, advanced, or recurrent ECs who received lenvatinib plus pembrolizumab, and 469 patients receiving PT at a platinum-free interval of over 6 months. Following PSM, no significant difference in median OS was observed between the lenvatinib plus pembrolizumab and re-challenge PT groups (19.1 vs. 18.5 months, p  = 0.60; hazard ratio: 1.08, 95% confidence interval 0.81–1.46). However, lenvatinib plus pembrolizumab provided better survival benefits than doxorubicin. Adverse event analysis showed more hypothyroidism, hypertension, and proteinuria with lenvatinib plus pembrolizumab, and more hematologic toxicities in both chemotherapy groups. Conclusions Lenvatinib plus pembrolizumab was not associated with improved survival when compared with re-challenge PT in patients with a platinum-free interval of over 6 months. Re-challenge PT remains a valid option for PT-treated, recurrent, or advanced ECs, especially in patients with a substantially long platinum-free interval.