Semi-automatic proximal humeral trabecular bone density assessment tool: technique application and clinical validation.

PURPOSE: This study aimed to apply a newly developed semi-automatic phantom-less QCT (PL-QCT) to measure proximal humerus trabecular bone density based on chest CT and verify its accuracy and precision. METHODS: Subcutaneous fat of the shoulder joint and trapezius muscle were used as calibration references for PL-QCT BMD measurement. A self-developed algorithm based on a convolution map was utilized in PL-QCT for semi-automatic BMD measurements. CT values of ROIs used in PL-QCT measurements were directly used for phantom-based quantitative computed tomography (PB-QCT) BMD assessment. The study included 376 proximal humerus for comparison between PB-QCT and PL-QCT. Two sports medicine doctors measured the proximal humerus with PB-QCT and PL-QCT without knowing each other's results. Among them, 100 proximal humerus were included in the inter-operative and intra-operative BMD measurements for evaluating the repeatability and reproducibility of PL-QCT and PB-QCT. RESULTS: A total of 188 patients with 376 shoulders were involved in this study. The consistency analysis indicated that the average bias between proximal humerus BMDs measured by PB-QCT and PL-QCT was 1.0 mg/cc (agreement range - 9.4 to 11.4; P > 0.05, no significant difference). Regression analysis between PB-QCT and PL-QCT indicated a good correlation (R-square is 0.9723). Short-term repeatability and reproducibility of proximal humerus BMDs measured by PB-QCT (CV: 5.10% and 3.41%) were slightly better than those of PL-QCT (CV: 6.17% and 5.64%). CONCLUSIONS: We evaluated the bone quality of the proximal humeral using chest CT through the semi-automatic PL-QCT system for the first time. Comparison between it and PB-QCT indicated that it could be a reliable shoulder BMD assessment tool with acceptable accuracy and precision. This study developed and verify a semi-automatic PL-QCT for assessment of proximal humeral bone density based on CT to assist in the assessment of proximal humeral osteoporosis and development of individualized treatment plans for shoulders.

Intramedullary administration of tranexamic acid reduces bleeding in proximal femoral nail antirotation surgery for intertrochanteric fractures in elderly individuals: A randomized controlled trial.

PURPOSE: Intertrochanteric fractures undergoing proximal femoral nail antirotation (PFNA) surgery are associated with significant hidden blood loss. This study aimed to explore whether intramedullary administration of tranexamic acid (TXA) can reduce bleeding in PFNA surgery for intertrochanteric fractures in elderly individuals. METHODS: A randomized controlled trial was conducted from January 2019 to December 2022. Patients aged over 60 years with intertrochanteric fractures who underwent intramedullary fixation surgery with PFNA were eligible for inclusion and grouped according to random numbers. A total of 249 patients were initially enrolled, of which 83 were randomly allocated to the TXA group and 82 were allocated to the saline group. The TXA group received intramedullary perfusion of TXA after the bone marrow was reamed. The primary outcomes were total peri-operative blood loss and post-operative transfusion rate. The occurrence of adverse events was also recorded. Continuous data was analyzed by unpaired t-test or Mann-Whitney U test, and categorical data was analyzed by Pearson Chi-square test. RESULTS: The total peri-operative blood loss (mL) in the TXA group was significantly lower than that in the saline group (577.23 ± 358.02 vs. 716.89 ± 420.30, p = 0.031). The post-operative transfusion rate was 30.67 % in the TXA group and 47.95 % in the saline group (p = 0.031). The extent of post-operative deep venous thrombosis and the 3-month mortality rate were similar between the 2 groups. CONCLUSION: We observed that intramedullary administration of TXA in PFNA surgery for intertrochanteric fractures in elderly individuals resulted in less peri-operative blood loss and decreased transfusion rate, without any adverse effects, and is, thus, recommended.

Isoprenylation modification is required for HIPP1-mediated powdery mildew resistance in wheat.

Powdery mildew (Pm), caused by Blumeria graminis f.sp. tritici (Bgt), is one of the most important wheat diseases. Heavy-metal-associated isoprenylated plant protein (HIPP1) has been proved playing important roles in response to biotic and a biotic stress. In present study, we proved HIPP1-V from Haynalidia villosa is a positive regulator in Pm resistance. HIPP1-V was rapidly induced by Bgt. Transiently or stably heterologous overexpressing HIPP1-V in wheat suppressed the haustorium formation and enhanced Pm resistance. HIPP1-V isoprenylation was critical for plasma membrane (PM) localization, interaction with E3-ligase CMPG1-V and function in Pm resistance. Bgt infection recruited the isoprenylated HIPP1-V and CMPG1s on PM; blocking the HIPP1 isoprenylation reduced such recruitment and compromised the resistance of OE-CMPG1-V and OE-HIPP1-V. Overexpressing HIPP1-VC148G could not enhance Pm resistance. These indicated the Pm resistance was dependent on HIPP1-V's isoprenylation. DGEs related to the ROS and SA pathways were remarkably enriched in OE-HIPP1-V, revealing their involvement in Pm resistance. Our results provide evidence on the important role of protein isoprenylation in plant defense.

Fine mapping of two recessive powdery mildew resistance genes from Aegilops tauschii accession CIae8.

KEY MESSAGE: Two recessive powdery mildew resistance loci pmAeCIae8_2DS and pmAeCIae8_7DS from Aegilops tauschii were mapped and two synthesized hexaploid wheat lines were developed by distant hybridization. Wheat powdery mildew (Pm), one of the worldwide destructive fungal diseases, causes significant yield loss up to 30%. The identification of new Pm resistance genes will enrich the genetic diversity of wheat breeding for Pm resistance. Aegilops tauschii is the ancestor donor of sub-genome D of hexaploid wheat. It provides beneficial genes that can be easily transferred into wheat by producing synthetic hexaploid wheat followed by genetic recombination. We assessed the Pm resistance level of 35 Ae. tauschii accessions from different origins. Accession CIae8 exhibited high Pm resistance. Inheritance analysis and gene mapping were performed using F2 and F2:3 populations derived from the cross between CIae8 and a Pm susceptible accession PI574467. The Pm resistance of CIae8 was controlled by two independent recessive genes. Bulked segregate analysis using a 55 K SNP array revealed the SNPs were mainly enriched into genome regions, i.e. 2DS (13.5-20 Mb) and 7DS (4.0-15.5 Mb). The Pm resistance loci were named as pmAeCIae8_2DS and pmAeCIae8_7DS, respectively. By recombinant screening, we narrowed the pmAeCIae8_2DS into a 370-kb interval flanked by markers CINAU-AE7800 (14.89 Mb) and CINAU-AE20 (15.26 Mb), and narrowed the pmAeCIae8_7DS into a 260-kb interval flanked by markers CINAU-AE58 (4.72 Mb) and CINAU-AE25 (4.98 Mb). The molecular markers closely linked with the resistance loci were developed, and two synthesized hexaploid wheat (SHW) lines were produced. These laid the foundation for cloning of the two resistance loci and for transferring the resistance into common wheat.

Resistance of QYm.nau-2D to wheat yellow mosaic virus was derived from an alien introgression into common wheat.

KEY MESSAGE: The QYm.nau-2D locus conferring wheat yellow mosaic virus resistance is an exotic introgression and we developed 11 diagnostic markers tightly linked to QYm.nau-2D. Wheat yellow mosaic virus (WYMV) is a serious disease of winter wheat in China. Breeding resistant varieties is the most effective strategy for WYMV control. A WYMV resistant locus QYm.nau-2D on the chromosome arm 2DL has been repeatedly reported but the mapped region is large. In the present study, we screened recombinants using a biparental population and mapped QYm.nau-2D into an 18.8 Mb physical interval. By genome-wide association studies of 372 wheat varieties for WYMV resistance in four environments, we narrowed down QYm.nau-2D into a 16.4 Mb interval. Haplotype analysis indicated QYm.nau-2D were present as six different states due to recombination during hybridization breeding. QYm.nau-2D was finally mapped into a linkage block of 11.2 Mb. Chromosome painting using 2D specific probes and collinearity analysis among the published sequences corresponding to QYm.nau-2D region indicated the block was an exotic introgression. The Illumina-sequenced reads of four diploid Aegilops species were mapped to the sequence of Fielder, a variety having the introgression. The mapping reads were significantly increased at the putative introgression regions of Fielder. Ae. uniaristata (NN) had the highest mapping reads, suggesting that QYm.nau-2D was possibly an introgression from genome N. We investigated the agronomic performances of different haplotypes and observed no linkage drag of the alien introgression for the 15 tested traits. For marker-assisted selection of QYm.nau-2D, we developed 11 diagnostic markers tightly linked to the locus. This research provided a case study of an exotic introgression, which has been utilized in wheat improvement for WYMV resistance.

Mercury (Hg) in the "Skin" of the Ocean: Dissolved Gaseous Hg, Total Hg, and Hg Redox Chemistry in Sea Surface Microlayer and Implication for Air-Sea Hg Exchange.

The sea surface microlayer (SML) is the uppermost ∼1000 µm of the surface of the ocean. With distinct physicochemical properties and position relative to the adjacent subsurface waters (SSWs), the ubiquitous distribution and high dynamics of the SML greatly regulate the global air-sea gas exchange and biogeochemistry. Mercury (Hg) redox chemistry in surface seawaters and air-sea exchange of gaseous Hg (mainly Hg(0)) fundamentally control the global oceanic Hg cycle. However, the occurrence and transformation of Hg in the SML have been poorly quantified. Here we optimize the traditional SML sampling system to make it more suitable for dissolved gaseous Hg (DGM, mainly Hg(0)) sampling. We then assess the temporal and spatial variability of DGM, total Hg, dissolved organic carbon (DOC), and Hg redox chemistry in the SML and SSWs of diverse marine environments. Our data suggest a general DGM, total Hg, and DOC enrichment in the SML relative to the SSWs but with complex variability in time and space. The incubation experiments further reveal the complex characteristics of Hg redox chemistry between the SML and SSWs. We discuss important implications of the SML Hg cycle on air-sea Hg exchange and suggest wider investigations of the SML Hg cycle in the global hydrosphere.

Fine mapping of wheat powdery mildew resistance gene Pm6 using 2B/2G homoeologous recombinants induced by the ph1b mutant.

KEY MESSAGE: Using the ph1b mutant, the recombination frequency between the homoeologous region of 2B and 2G was significantly increased. By this, we narrowed Pm6 to a 0.9 Mb physical region. The powdery mildew (Pm) resistance gene Pm6 from Triticum timopheevii (2n = 48, AAGG) was mapped to the long arm of chromosome 2G and introduced into common wheat in the form of 2B-2G introgressions. The introgression line IGV1-465 has the shortest 2G segment, which is estimated 37 Mb in size when referring to 2BL genome reference of Chinese Spring (CS). The further fine mapping of Pm6 was impeded by the inhibition of allogeneic chromosome recombination between 2B and 2G in the Pm6 region. In the present study, to overcome 2B/2G recombination suppression, a ph1b-based strategy was employed to produce introgressions with reduced 2G fragments for the fine mapping of Pm6. IGV1-465 was crossed and backcrossed to the CSph1b mutant to produce plants with increased 2B/2G chromosome pairing frequency at the Pm6 region. A total of 182 allogeneic recombinants were obtained through two-round screening, i.e., first round of screening of 820 BC1F2:3 progenies using the flanking markers CIT02g-14/CIT02g-19 and second round of screening of 642 BC1F2:4 progenies using the flanking markers CIT02g-13/CIT02g-18, respectively. Through marker analysis using 30 chromosome 2G-specific markers located in the Pm6 region, the identified recombinants were divided into 14 haplotypes. Pm resistance evaluation of these haplotypes enabled us to narrow Pm6 to a 0.9 Mb physical region of 2BL, flanked by markers CIT02g-20 and CIT02g-18. Six wheat varieties containing Pm6 were identified from a natural population, and they showed increased Pm resistance. This implied Pm6 is still effective, especially when used in combination with other Pm resistance genes.

The Friction-Lubrication Effect and Compaction Characteristics of an SMA Asphalt Mixture under Variable Temperature Conditions.

The aim of this article is to explore the dynamic compaction characteristics of stone mastic asphalt (SMA) and the friction-lubrication effect of internal particles during the superpave gyratory compaction (SGC) process. Firstly, a calculated method for the compaction degree of an asphalt mixture in the gyratory compaction process was defined based on the multiphase granular volume method. Secondly, the gyratory compaction curves of asphalt mixtures were taken based on this calculation method of compaction degree. The dynamic change law of each compaction index (compaction, percentage of air voids, compaction energy index, etc.) during the compaction process was analysed. Finally, the effects of different initial compaction temperatures and different asphalt content on the friction-lubrication effect and compaction characteristics of asphalt mixtures were studied. Research shows that it is reasonable to define the compaction degree by the ratio of the apparent density of the asphalt mixture to the maximum theoretical density of the asphalt mixture during gyratory compaction. The dynamic prediction equations of the compaction degree K and the compaction energy index CEI with the amount of compaction were established, and could effectively predict the compaction degree, percentage of air voids and compaction energy index CEI. The compaction process of the asphalt mixture needed to go through three phases, including periods of rapid growth, slow growth, and stabilisation, and the compaction degree increased by about 10%, 5%, and 1%, in that order, finally tending towards a stable value. The effect of the initial compaction temperature on the forming compaction degree of the asphalt mixture is significant; therefore, it should be controlled strictly in the compaction construction of asphalt mixtures. When the initial compaction temperature of SMA-13 is about 170 °C, the compaction effect is optimal, and the effect of the increase in the amount of compaction at a later stage on the increase in the compaction degree of the asphalt mixture is very low. With the optimal asphalt content, the friction-lubrication effect between the asphalt and aggregate particles is optimal, because it can effectively form an asphalt film, reducing the frictional resistance of the particles moving each other during the compaction process, and the voids will be embedded and filled with each other, finally producing the best compaction result.

A time-course transcriptome analysis revealing the potential molecular mechanism of early gonadal differentiation in the Chinese giant salamander.

The Chinese giant salamander (CGS) Andrias davidianus is the largest extant amphibian and has recently become an important species for aquaculture with high economic value. Meanwhile, its wild populations and diversity are in urgent need of protection. Exploring the mechanism of its early gonadal differentiation will contribute to the development of CGS aquaculture and the recovery of its wild population. In this study, transcriptomic and phenotypic research was conducted on the critical time points of early gonadal differentiation of CGS. The results indicate that around 210 days post-hatching (dph) is the critical window for female CGS's gonadal differentiation, while 270 dph is that of male CGS. Besides, the TRPM1 gene may be the crucial gene among many candidates determining the sex of CGS. More importantly, in our study, key genes involved in CGS's gonadal differentiation and development are identified and their potential pathways and regulatory models at early stage are outlined. This is an initial exploration of the molecular mechanisms of CGS's early gonadal differentiation at multiple time points, providing essential theoretical foundations for its captive breeding and offering unique insights into the conservation of genetic diversity in wild populations from the perspective of sex development.

Selective recovery of Au from waste printed circuit board by water-soluble organic leaching: The key role of in situ bromine mediation and identificationof pathway.

A large amount of gold in electronic waste (E-waste) is not properly recovered owing to the absence of efficient and safe leaching methods. Herein, we proposed the concept of 'water-soluble organic Au leaching' and created a new water-soluble organic leaching agent, WS NBS-DMF, by dissolving millimolar amounts of N-bromosuccinimide (NBS) and dimethylformamide (DMF) in water. Under mild conditions (25 â„ƒ, pH 7.0), WS NBS-DMF achieved a 94.9 % leaching efficiency of Au for waste printed circuit board (WPCB) with limited leaching of base metals. The potent bromine radical (Br•) and ligands significantly contributed to Au complexation and oxidization via in situ bromine generation and radical initiation from WS NBS-DMF. The bidirectional hydrogen-bond effect of DMF facilitated the in situ bromine generation. Two Au(I) complexes ([AuBr2]- and [(NHS)AuBr]-) and an Au(III) complex ([(NHS)AuBr3]-) were confirmed as the Au leaching products by spectroscopy and mass spectrometry. Furthermore, reciprocal σ-donations between the Au center and ligands in the bonding orbitals enhanced the stability of the Au complexes, thereby promoting efficient Au leaching. Comparing with other leaching methods, this study of WS NBS-DMF provides a safe, economic and eco-friendly technique for efficient and selective gold recovery from e-waste.

Stigma and Glume Characteristics Synergistically Determine the Stigma Exsertion Rate in Thermo-Photo-Sensitive Genic Male Sterile Wheat.

Wheat hybrids have been widely demonstrated to have remarkable heterosis or hybrid vigor in increasing yield potential and stability since the 1960s. Two-line hybrid wheat can achieve higher yields than local varieties, especially in marginal environments. However, the commercial application of hybrid wheat is hindered by higher seed costs, primarily due to lower yields in hybrid seed production. Stigma exsertion has been verified as a decisive factor in increasing rice's hybrid seed yield, but more investigation is needed in hybrid wheat breeding and production. In this study, four thermo-photo-sensitive genic male sterile lines, including K41S, K64S, K66S, and K68S, with different stigma exsertion rates (SERs) were used to compare the differences in floral architecture relative to stigma exsertion over two growing seasons. The results revealed that the K41S and K64S exhibited a relatively higher SER at 21.87% and 22.81%, respectively. No exserted stigma was observed in K66S, and K68S had an SER of only 0.82%. This study found that the stigma length, glume width and the length-width ratio of the glume were significantly correlated with the SER, with correlation coefficients of 0.46, -0.46 and 0.60, respectively. Other stigma features such as the branch angle, stretch width and hairbrush length, as well as the glume length, also had a weakly positive correlation with SER (r = 0.09-0.27). For K41S and K64S, the SER was significantly affected by the differences in the stigma branch angle and stigma stretch width among florets. A cross-pollination survey showed that the out-crossing ability of florets with an exserted stigma was about three times as high as that of florets with a non-exserted stigma. As a result, the stigma-exserted florets that accounted for 21.87% and 22.81% of the total florets in K41S and K64S produced 46.80% and 48.53% of the total cross-pollinated seeds in both sterile lines. These findings suggest that a longer stigma combined with a slender glume appears to be the essential floral feature of stigma exsertion in sterile wheat lines. It is expected that breeding and utilizing sterile lines with a higher SER would be a promising solution to cost-effective hybrid wheat seed production.

Perioperative toripalimab and chemotherapy in locally advanced gastric or gastro-esophageal junction cancer: a randomized phase 2 trial.

Perioperative chemotherapy is the standard treatment for locally advanced gastric or gastro-esophageal junction cancer, and the addition of programmed cell death 1 (PD-1) inhibitor is under investigation. In this randomized, open-label, phase 2 study (NEOSUMMIT-01), patients with resectable gastric or gastro-esophageal junction cancer clinically staged as cT3-4aN + M0 were randomized (1:1) to receive either three preoperative and five postoperative 3-week cycles of SOX/XELOX (chemotherapy group, n = 54) or PD-1 inhibitor toripalimab plus SOX/XELOX, followed by toripalimab monotherapy for up to 6 months (toripalimab plus chemotherapy group, n = 54). The primary endpoint was pathological complete response or near-complete response rate (tumor regression grade (TRG) 0/1). The results showed that patients in the toripalimab plus chemotherapy group achieved a higher proportion of TRG 0/1 than those in the chemotherapy group (44.4% (24 of 54, 95% confidence interval (CI): 30.9%-58.6%) versus 20.4% (11 of 54, 95% CI: 10.6%-33.5%)), and the risk difference of TRG 0/1 between toripalimab plus chemotherapy group and chemotherapy group was 22.7% (95% CI: 5.8%-39.6%; P = 0.009), meeting a prespecified endpoint. In addition, a higher pathological complete response rate (ypT0N0) was observed in the toripalimab plus chemotherapy group (22.2% (12 of 54, 95% CI: 12.0%-35.6%) versus 7.4% (4 of 54, 95% CI: 2.1%-17.9%); P = 0.030), and surgical morbidity (11.8% in the toripalimab plus chemotherapy group versus 13.5% in the chemotherapy group) and mortality (1.9% versus 0%), and treatment-related grade 3-4 adverse events (35.2% versus 29.6%) were comparable between the treatment groups. In conclusion, the addition of toripalimab to chemotherapy significantly increased the proportion of patients achieving TRG 0/1 compared to chemotherapy alone and showed a manageable safety profile. ClinicalTrials.gov registration: NCT04250948 .

Gaseous mercury exchange between air and highly dynamic tidal flats: A laboratory incubation experiment.

Gaseous mercury (mainly elemental mercury, Hg(0)) exchange between air and Earth's surfaces is one of the most critical fluxes governing global Hg cycle. As an important and unique part of intertidal ecosystem, tidal flat is characterized by periodic inundation and exposure due to tidal cycle, generating varying hydrological, photochemical and biogeochemical processes. However, quantitative and mechanistic understanding of Hg(0) dynamics between air and exceptionally dynamic tide flats has remained limited to date. In this study, we select five representative tidal flat sediments from typical coastal habits of Chinese coastlines to perform laboratory incubation experiments for deciphering the effect of the interaction of tidal cycle and solar radiation on Hg(0) dynamics over tidal flats with different sediment compositions. We show that sediment Hg concentration, tidal cycle and solar radiation collectively modulate the air-surface Hg(0) exchange over tidal flats and highlight that the photochemistry dominates the Hg(0) production and emission over tidal flats. We find that the daytime inundation presents highest Hg(0) emission fluxes for Hg-poor sediment, but the daytime exposure is the hot moment of Hg(0) emission from Hg-rich sediments and substantially contributes to daily Hg(0) emission fluxes. In the treatment to mimic semidiurnal tide, the daily Hg(0) fluxes are positively correlated to sediment Hg concentrations. Combining our mechanistic insights on air-surface Hg(0) exchange over tidal flats and related data and knowledge reported by other studies, we discuss the implications of our study for field measurement and model development of Hg(0) dynamics over highly dynamic tidal flats. We conclude that the air-surface Hg(0) dynamics over tidal flats are extremely complex and highly variable, and a greater understanding the interactions between natural processes, human impacts and climate forcings will better constrain current and future Hg biogeochemical cycle in global tidal flats.

Coastal streams and sewage outfalls: Hot spots of mercury discharge, pollution and cycling in nearshore environments.

The coastal streams (CSs) and sewage outfalls (SOs) are widely distributed and direct anthropogenic stress on global coastal ecosystems. However, the CS/SO-associated mercury (Hg) discharge, pollution and cycle in nearshore environment are less quantified. Here, we report that total Hg (THg) and methylmercury (MMHg) concentrations in waters of CSs (n = 8) and SOs (n = 15) of the northern China were ∼102 to 103 times of coastal surface waters and 10 to 102 times of major rivers in China and other regions. The CS/SO discharges resulted in the increase of total organic carbon (TOC) contents, THg and MMHg concentrations and TOC-normalized THg and MMHg concentrations in sediments of CS/SO-impacted coasts. The laboratory experiments further illustrated that the CS/SO-impacted sediments characterized with high potentials of dissolved THg and MMHg productions and releases. Our findings indicate that the layout optimization of SOs is able to reduce the Hg risk in coastal environment.

Improved electroluminescence efficiency derived from functionalized decoration of 1,3,4-oxadiazole (OXD)-based Ir(III) complexes.

The performance of organic light emitting devices (OLEDs) fabricated using Ir(III) complexes bearing 1,3,4-oxadiazole (OXD)-based cyclometallic ligands still needs to be improved. In this work, Ir3+ was coordinated with a 2-(9,9-diethyl-9H-fluoren-2-yl)-1,3,4-oxadiazole (F-OXD) fragment, which was modified with various functionalized substituents, including fluorenyl, OXD and carbazolyl groups. Three complexes, named Ir-Flu, Ir-OXD and Ir-Cz, were synthesized successfully and their photophysical, electrochemical and electroluminescence properties were investigated in detail. All these complexes exhibited yellow-orange emission in solution and a distinct aggregation-induced phosphorescent emission (AIPE) phenomenon was observed. Monochrome OLEDs were fabricated using these phosphorescent dopants, and the turn-on voltage (V), luminance (L) and current efficiency (CE) showed significant improvement compared to analogous OXD-based Ir(III) complexes reported before. In particular, the device with Ir-OXD as the dopant achieved the highest maximum brightness of 25 014 cd m-2 and the lowest efficiency roll-off (42.6%) at the maximum luminance among all the devices. These results provided a proven strategy of functionalized decoration of OXD-based complexes to achieve superior luminous efficiency devices.

Pregnancy outcomes following natural conception and assisted reproduction treatment in women who received COVID-19 vaccination prior to conception: a population-based cohort study in China.

Introduction: The coronavirus disease-2019 (COVID-19) pandemic has swept across the world and continues to exert serious adverse effects on vulnerable populations, including pregnant women and neonates. The vaccines available at present were designed to prevent infection from COVID-19 strains and control viral spread. Although the incidence of pregnancy cycle outcomes are not likely to increase patients vaccinated prior to pregnancy compared with unvaccinated patients based on our knowledge of vaccination safety, there is no specific evidence to support this hypothesis. Therefore, the current study aimed to investigate the association between maternal vaccination prior to conception and pregnancy outcomes. Methods: We retrospectively analyzed 2,614 women who received prenatal care and delivered in the Obstetrical Department of The First Affiliated Hospital of Anhui Medical University between February 2022 and November 2022. Of the 1,380 eligible pregnant women, 899 women who had received preconception vaccination were assigned to a vaccine group and 481 women who were not vaccinated were control group. Of the enrolled patients, 291 women received fertility treatment (141 vaccinated women, 150 unvaccinated women). The primary outcomes were pregnancy complications (hypothyroidism, gestational diabetes mellitus, pregnancy-induced hypertension, polyhydramnios, oligohydramnios, premature rupture of membranes and postpartum hemorrhage), obstetric outcomes (preterm birth rate, cesarean section rate) and neonatal outcomes (birth-weight, body length, low-birth-weight rate, rate of congenital defects, neonatal mortality and admission to the neonatal intensive care unit). Results: There was no significant difference in the incidence of complications during pregnancy and delivery when compared between the vaccine group and control group in either univariate- or multivariate-models. The type of vaccine was not associated with the odds of adverse pregnancy outcome. Among the women with infertility treatment, the vaccinated group and the unvaccinated group had similar pregnancy outcomes. Conclusion: Women who received COVID-19 vaccination prior to conception had similar maternal and neonatal outcomes as women who were unvaccinated. Our findings indicate that COVID-19 vaccinations can be safely administered prior to pregnancy in women who are planning pregnancy or assisted reproductive treatment. During new waves of COVID-19 infection, women who are planning pregnancy should be vaccinated as soon as possible to avoid subsequent infections.

CDA-2 induces cell differentiation through suppressing Twist/SLUG signaling via miR-124 in glioma.

Cell differentiation agent-2 (CDA-2) is an extraction from healthy human urine consisting of primary organic acids and peptides, and it has been demonstrated to inhibit growth and induce differentiation in glioma and other cell lines. But the mechanism of CDA-2 remains unclear. In this study, we demonstrated that CDA-2 inhibited cell growth and induced differentiation of glioma cells, accompanied with decreased expression of SLUG, Twist and Vimentin in both SWO-38 and U251 cell lines. Overexpression of SLUG or Twist greatly eliminated the efficiency of CDA-2 in inducing differentiation. Further study showed that CDA-2 treatment resulted in great changed microRNAs (miRNAs) detected by quantitative PCR, in which miR-124 was one of the most changed miRNAs and its level was increased by fourfold. The result of miRNA target prediction showed that miR-124 could regulate hundreds of genes which were relative to cell differentiation, such as SLUG, Vimentin, actin cytoskeleton, focal adhesion, tight junction. Inhibition of miR-124 up-regulated SLUG, Twist and Vimentin proteins, and partly eliminated the function of CDA-2 on these mesenchymal markers. Our findings demonstrated for the first time that CDA-2 induced cell differentiation through suppressing Twist and SLUG via miR-124 in glioma cells.

Mechanisms of Caspases 3/7/8/9 in the Degeneration of External Gills of Chinese Giant Salamanders (Andrias davidianus).

Metamorphosis is a critical stage in the adaptive development of amphibians from aquatic to terrestrial animals. Metamorphosis of the Chinese giant salamander is mainly manifested by the loss of external gills with consequent changes in the respiratory pattern. The loss of the external gill is regulated by the pathway of apoptosis in which caspase genes are the key factors. This study cloned and expressed the caspase 3/7/8/9 genes of the Chinese giant salamander. The main results were as follows: the complete open reading frames (ORFs) were 885 bp, 960 bp, 1461 bp and 1279 bp, respectively; caspase 3/7/8/9 genes all contained the CASc domain, and most of the motifs were located in CASc domain; and caspase 8 possessed two DED structural domains and caspase 9 possessed a CARD structural domain. Furthermore, results from the tissue distribution analysis indicated that caspase 3/7/8/9 genes were all significantly expressed in the external gill, and at 9 and 10 months of age (MOA), which is the peak time for the loss, the EXPRESSION level of caspase 3/7/8/9 genes was obviously high, which was consistent with the histological result. Moreover, the loss of external gills of the Chinese giant salamander may result from activation of both the apoptosis-related death receptor pathway and the mitochondrial pathway. Finally, it was discovered that thyroid hormone (TH) treatment could both advance the time point at which the external gills of the Chinese giant salamander began to degenerate and shorten this process. Interestingly, at the peak of its metamorphosis (9 MOA), the Chinese giant salamander further accelerated the metamorphosis rate of TH treatment, which suggested a promotive effect on the loss of external gills via the superimposition of the exogenous TH and caspase genes. The study of caspase genes in this experiment was conducive to understanding the mechanism of external gill loss in the Chinese giant salamander, as well as improving our understanding of the metamorphosis development of some Caudata species.