Analysis of the prenatal ultrasound diagnostic value and prognostic factors of fetal mediastinal cysts.

Background: A prenatal fetal mediastinal cyst is a benign disease. However, if a cyst enlargement grows, it may compress the adjacent organs and affect the fetal cardiopulmonary function. This study aimed to compare and analyze the prenatal ultrasound characteristics of different mediastinal cysts, and to evaluate the pregnancy outcome of the fetus and the factors affecting the prognostic of the fetus. To compare and analyze the prenatal ultrasound characteristics of different types of mediastinal cysts, and to evaluate the fetal pregnancy outcome and the influencing factors of fetal prognosis. Methods: A retrospective analysis of patients with prenatal diagnoses of mediastinal cysts was conducted to evaluate the ultrasound characteristics and to monitor the pregnancy outcomes to identify prognostic influences and provide a reliable basis for patient prognosis. Results: In total, 30 patients were diagnosed with mediastinal cysts [including bronchogenic cysts (n=12), esophageal cysts (n=9), pericardial cysts (n=5), and thymic cysts (n=4)] on prenatal ultrasonography. The diagnostic accuracy rate was 93.33%; two cases of esophageal cysts were misdiagnosed as bronchial cysts. In total, 4 (44.44%) of 9 esophageal cysts and 4 thymic cysts were located in the anterior mediastinum, 10 (83.33%) of 12 bronchogenic cysts and 5 pericardial cysts were located in the middle mediastinum, and 2 (16.67%) of 12 bronchogenic cysts and 5 (55.56%) of 9 esophageal cysts were located in the posterior mediastinum. There were significant differences in the distribution of the cyst location, morphology, and cyst wall thickness (P<0.05). After delivery, 17 patients had clinical symptoms. There was a significant difference in the clinical symptoms between patients with a maximum diameter of postpartum cysts <5 and ≥5 cm (P<0.05), and children with a low gestational age and birth weight were more likely to have clinical symptoms. Conclusions: The prenatal ultrasound features of fetal mediastinal cysts were similar. However, the ultrasound characteristics related to the cyst location, morphology, and cyst wall thickness were helpful in providing an accurate diagnosis. In addition, the postpartum cyst size, location, adjacent relationship with the surrounding tissues, volume, gestational age, and weight were related to patient prognosis.

"Cloth-to-Clothes-Like" Fabrication of Soft Actuators.

Inspired by adaptive natural organisms and living matter, soft actuators appeal to a variety of innovative applications such as soft grippers, artificial muscles, wearable electronics, and biomedical devices. However, their fabrication is typically limited in laboratories or a few enterprises since specific instruments, strong stimuli, or specialized operation skills are inevitably involved. Here a straightforward "cloth-to-clothes-like" method to prepare soft actuators with a low threshold by combining the hysteretic behavior of liquid crystal elastomers (LCEs) with the exchange reaction of dynamic covalent bonds, is proposed. Due to the hysteretic behavior, the LCEs (resemble "cloth") effectively retain predefined shapes after stretching and releasing for extended periods. Subsequently, the samples naturally become soft actuators (resemble "clothes") via the exchange reaction at ambient temperatures. As a post-synthesis method, this strategy effectively separates the production of LCEs and soft actuators. LCEs can be mass-produced in bulk by factories or producers and stored as prepared, much like rolls of cloth. When required, these LCEs can be customized into soft actuators as needed. This strategy provides a robust, flexible, and scalable solution to engineer soft actuators, holding great promise for mass production and universal applications.

Lung function benefits of traditional Chinese medicine Qiju granules against fine particulate air pollution exposure: a randomized controlled trial.

Introduction: Multiple targets are considered as the causes of ambient fine particulate matter [aerodynamic diameters of < 2.5 µm (PM2.5)] induced lung function injury. Qiju granules are derived from the traditional Chinese medicine (TCM) formula known as Qi-Ju-Di-Huang-Wan (Lycium, Chrysanthemum, and Rehmannia Formula, QJDHW), which has been traditionally used to treat symptoms such as cough with phlegm, dry mouth and throat, and liver heat. This treatment approach involves attenuating inflammation, oxidative stress, and fibrosis response. This study investigated the effects of Qiju granules on protecting lung function against PM2.5 exposure in a clinical trial. Methods: A randomized, double-blinded, and placebo-controlled trial was performed among 47 healthy college students in Hangzhou, Zhejiang Province in China. The participants were randomly assigned to the Qiju granules group or the control group based on gender. Clinical follow-ups were conducted once every 2 weeks during a total of 4 weeks of intervention. Real-time monitoring of PM2.5 concentrations in the individually exposed participants was carried out. Data on individual characteristics, heart rate (HR), blood pressure (BP), and lung function at baseline and during the follow-ups were collected. The effects of PM2.5 exposure on lung function were assessed within each group using linear mixed-effect models. Results: In total, 40 eligible participants completed the scheduled follow-ups. The average PM2.5 level was found to be 64.72 µg/m3 during the study period. A significant negative correlation of lung function with PM2.5 exposure concentrations was observed, and a 1-week lag effect was observed. Forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), maximal mid-expiratory flow (MMEF), forced expiratory flow at 75% of forced vital capacity (FVC) (FEF75), forced expiratory flow at 50% of FVC (FEF50), and forced expiratory flow at 25% of FVC (FEF25) were significantly decreased due to PM2.5 exposure in the control group. Small airway function was impaired more seriously than large airway function when PM2.5 exposure concentrations were increased. In the Qiju granules group, the associations between lung function and PM2.5 exposure were much weaker, and no statistical significance was observed. Conclusion: The results of the study showed that PM2.5 exposure was associated with reduced lung function. Qiju granules could potentially be effective in protecting lung functions from the adverse effects of PM2.5 exposure. Clinical Trial Registration: identifier: ChiCTR1900021235.

New insights into algal-bacterial sludge granulation based on the tightly-bound extracellular polymeric substances regulation in response to N-Methylpyrrolidone.

Algal-bacterial granular sludge (ABGS) system is promising in wastewater treatment for its potential in energy-neutrality and carbon-neutrality. However, traditional cultivation of ABGS poses significant challenges attributable to its long start-up period and high energy consumption. Extracellular polymeric substances (EPS), which could be stimulated as a self-defense strategy in cells under toxic contaminants stress, has been considered to contribute to the ABGS granulation process. In this study, photogranulation of ABGS by EPS regulation in response to varying loading rates of N-Methylpyrrolidone (NMP) was investigated for the first time. The results indicated the formation of ABGS with a maximum average diameter of ∼3.3 mm and an exceptionally low SVI5 value of 67 ± 2 mL g-1 under an NMP loading rate of 125 mg L-1 d-1, thereby demonstrating outstanding settleability. Besides, almost complete removal of 300 mg L-1 NMP could be achieved at hydraulic retention time of 48 h, accompanied by chemical oxygen demand (COD) and total nitrogen (TN) removal efficiencies higher than 90 % and 70 %, respectively. Moreover, possible degradation pathway and metabolism mechanism in the ABGS system for enhanced removal of NMP and nitrogen were proposed. In this ABGS system, the mycelium with network structure constituted by filamentous microorganisms was a prerequisite for photogranulation, instead of necessarily leading to granulation. Stress of 100-150 mg L-1 d-1 NMP loading rate stimulated tightly-bound EPS (TB-EPS) variation, resulting in rapid photogranulation. The crucial role of TB-EPS was revealed with the involved mechanisms being clarified. This study provides a novel insight into ABGS development based on the TB-EPS regulation by NMP, which is significant for achieving the manipulation of photogranules.

Combining serum microRNAs and machine learning algorithms for diagnosing infectious fever after HSCT.

Infection post-hematopoietic stem cell transplantation (HSCT) is one of the main causes of patient mortality. Fever is the most crucial clinical symptom indicating infection. However, current microbial detection methods are limited. Therefore, timely diagnosis of infectious fever and administration of antimicrobial drugs can effectively reduce patient mortality. In this study, serum samples were collected from 181 patients with HSCT with or without infection, as well as the clinical information. And more than 80 infectious-related microRNAs in the serum were selected according to the bulk RNA-seq result and detected in the 345 time-pointed serum samples by Q-PCR. Unsupervised clustering result indicates a close association between these microRNAs expression and infection occurrence. Compared to the uninfected cohort, more than 10 serum microRNAs were identified as the combined diagnostic markers in one formula constructed by the Random Forest (RF) algorithms, with a diagnostic accuracy more than 0.90. Furthermore, correlations of serum microRNAs to immune cells, inflammatory factors, pathgens, infection tissue, and prognosis were analyzed in the infection cohort. Overall, this study demonstrates that the combination of serum microRNAs detection and machine learning algorithms holds promising potential in diagnosing infectious fever after HSCT.

Evolution characteristics and influencing factors of information network in Guangdong-Hong Kong-Macao Greater Bay Area.

In the context of the digital information era, the impact of "The Internet Plus," "Big Data," and other technologies on urban social development has been far beyond any preceding era, under the influence of information technology, urban agglomeration space exhibits a new layout. Based on the search engine data of eleven cities in the Guangdong-Hong Kong-Macao Greater Bay Area from 2012 to 2021, this research constructs the inter-city information network strength linkage matrix to examine the evolution characteristics of city network structure and its driving causes. The results reveal that (1) the overall information linkage strength exhibits a pattern of steadily growing the radiating effect from the leading cities of Guangdong, Shenzhen, and Hong Kong to the surrounding cities, and a closer and more balanced information linkage network is gradually built. (2) Guangzhou-Shenzhen-Hong Kong-Guangdong-Hong Kong-Macao Greater Bay Area information linkage absolute control advantage, four cities Foshan, Dongguan, Zhuhai, Macao regional hub position steadily highlighted. The entire information connection network of the urban agglomerations tends to be flat and polycentric at the same time. (3) The regional core-edge hierarchy is well established, with the four cities of Guangzhou, Dongguan, Shenzhen, and Hong Kong creating a northwest-southeast orientation. The core metropolis regions of Guangdong, Hong Kong, and Macao in the Greater Bay Area increasingly exert a radiation spreading effect to the northeast and southwest. (4) The urban economy, transportation distance, and information infrastructure have substantial effects on the information connection intensity network of urban clusters.

----A Bioorthogonal Dual Fluorogenic Probe for the Live-Cell Monitoring of Nutrient Uptake by Mammalian Cells.

Cells rely heavily on the uptake of exogenous nutrients for survival, growth, and differentiation. Yet quantifying the uptake of small molecule nutrients at the single cell level is difficult. Here we present a new approach to studying the nutrient uptake in live single cells using Inverse Electron-Demand Diels Alder (IEDDA) chemistry. We have modified carboxyfluorescein-diacetate-succinimidyl esters (CFSE) - a quenched fluorophore that can covalently react with proteins and is only turned on in the cytosol of a cell following esterase activity - with a tetrazine. This tetrazine serves as a second quencher for the pendant fluorophore. Upon reaction with nutrients modified with an electron-rich or strained dienophile in an IEDDA reaction, this quenching group is destroyed, thereby enabling the probe to fluoresce. This has allowed us to monitor the uptake of a variety of dienophile-containing nutrients in live primary immune cell populations using flow cytometry and live-cell microscopy.

A retrospective study on the effect of statins on mortality and antimicrobial resistance among patients with Staphylococcus aureus bloodstream infection.

Introduction: There is insufficient evidence in statin on the treatment of Staphylococcus aureus (SA) infection, we observe and analyze the clinical outcomes and antibiotic resistance of SA bloodstream infections in patients who received statins. Methods: A retrospective study was carried out in SA bloodstream infection of hospitalized patients from January 2018 to August 2023. The 30-day attributable mortality, 30-day all-cause mortality and clinical data of patients who received statins and non-statins were compared. Results: A total of 74 patients with SA bloodstream infection were included, 32 (43.2%) patients received treatment with statins and 42 (56.8%) with non-statins. The incidence of methicillin-resistant SA (MRSA) was significantly lower in the statins group (15.6% vs. 38.1%, p = 0.034), however, no significant differences were observed in the mortality rate (p = 0.410). Conclusions: This study revealed the superiority of statins in reducing incidence of MRSA among SA bloodstream infection patients, but statins do not improve the 30-day mortality rate.

Mesencephalic Astrocyte-derived Neurotrophic Factor Supports Hepatitis B Virus-Induced Immunotolerance.

BACKGROUND & AIMS: The immune tolerance induced by Hepatitis B virus (HBV) is a major challenge for achieving effective viral clearance, and the mechanisms involved are not well understood. One potential factor involved in modulating immune responses is mesencephalic astrocyte-derived neurotrophic factor (MANF), which has been reported to be increased in patients with chronic hepatitis B. In this study, our objective is to examine the role of MANF in regulating immune responses to HBV. METHODS: We utilized a commonly used HBV-harboring mouse model, where mice were hydrodynamically injected with the pAAV/HBV1.2 plasmid. We assessed the HBV load by measuring the levels of various markers including HBsAg, HBeAg, HBcAg, HBV DNA, and HBV RNA. RESULTS: Our study revealed that following HBV infection, both myeloid cells and hepatocytes exhibited increased expression of MANF. Moreover, we observed that mice with myeloid-specific MANF knockout (ManfMye-/-) displayed reduced HBV load and improved HBV-specific T cell responses. The decreased HBV-induced tolerance in ManfMye-/- mice was associated with reduced accumulation of myeloid-derived suppressor cells (MDSCs) in the liver. Restoring MDSC levels in ManfMye-/- mice through MDSC adoptive transfer reinstated HBV-induced tolerance. Mechanistically, we found that MANF promoted MDSC expansion by activating the IL-6/STAT3 pathway. Importantly, our study demonstrated the effectiveness of a combination therapy involving an HBsAg vaccine and nanoparticle-encapsulated MANF siRNA in effectively clearing HBV in HBV-carrier mice. CONCLUSION: The current study reveals that MANF plays a previously unrecognized regulatory role in liver tolerance by expanding MDSCs in the liver through IL-6/ STAT3 signaling, leading to MDSC-mediated CD8+ T cell exhaustion.

Application of ultrasound in early prediction of delayed graft function after renal transplantation.

Kidney transplantation is currently the most effective treatment for end-stage renal disease. Delayed graft function (DGF) is one of the most common complications after renal transplantation and is a significant complication affecting graft function and the survival time of transplanted kidneys. Therefore, early diagnosis of DGF is crucial for guiding post-transplant care and improving long-term patient survival. This article will summarize the pathological basis and clinical characteristics of DGF after kidney transplantation, with a focus on contrast-enhanced ultrasound. It will analyze the current application status of ultrasound technology in DGF diagnosis and provide a comprehensive review of the clinical applications of ultrasound technology in this field, serving as a reference for the further application of ultrasound technology in kidney transplantation.

GPS2 ameliorates cigarette smoking-induced pulmonary vascular remodeling by modulating the ras-Raf-ERK axis.

BACKGROUND: Mitogen-activated protein kinase (MAPK)signaling-mediated smoking-associated pulmonary vascular remodeling (PVR) plays an important role in the pathogenesis of group 3 pulmonary hypertension (PH). And G protein pathway suppressor 2 (GPS2) could suppress G-protein signaling such as Ras and MAPK, but its role in cigarette smoking -induced PVR (CS-PVR) is unclear. METHODS: An in vivo model of smoke-exposed rats was constructed to assess the role of GPS2 in smoking-induced PH and PVR. In vitro, the effects of GPS2 overexpression and silencing on the function of human pulmonary arterial smooth cells (HPASMCs) and the underlying mechanisms were explored. RESULTS: GPS2 expression was downregulated in rat pulmonary arteries (PAs) and HPASMCs after CS exposure. More importantly, CS-exposed rats with GPS2 overexpression had lower right ventricular systolic pressure (RVSP), right ventricular hypertrophy index (RVHI), and wall thickness (WT%) than those without. And enhanced proliferation and migration of HPASMCs induced by cigarette smoking extract (CSE) can be evidently inhibited by overexpressed GPS2. Besides, GPS2siRNA significantly enhanced the proliferation, and migration of HPASMCs as well as activated Ras and Raf/ERK signaling, while these effects were inhibited by zoledronic acid (ZOL). In addition, GPS2 promoter methylation level in rat PAs and HPASMCs was increased after CS exposure, and 5-aza-2-deoxycytidine (5-aza) inhibited CSE-induced GPS2 hypermethylation and downregulation in vitro. CONCLUSIONS: GPS2 overexpression could improve the CS-PVR, suggesting that GPS2 might serve as a novel therapeutic target for PH-COPD in the future.

Regulating Surface Dipole Moments of TiO2 for the pH-Universal Cathodic Fenton-Like Process.

Although electro-Fenton (EF) processes can avoid the safety risks raised by concentrated hydrogen peroxide (H2O2), the Fe(III) reduction has always been either unstable or inefficient at high pH, resulting in catalyst deactivation and low selectivity of H2O2 activation for producing hydroxyl radicals (•OH). Herein, we provided a strategy to regulate the surface dipole moment of TiO2 by Fe anchoring (TiO2-Fe), which, in turn, substantially increased the H2O2 activation for •OH production. The TiO2-Fe catalyst could work at pH 4-10 and maintained considerable degradation efficiency for 10 cycles. Spectroscopic analysis and a theoretical study showed that the less polar Fe-O bond on TiO2-Fe could finely tune the polarity of H2O2 to alter its empty orbital distribution, contributing to better ciprofloxacin degradation activity within a broad pH range. We further verified the critical role of the weakened polarity of H2O2 on its homolysis into •OH by theoretically and experimentally investigating Cu-, Co-, Ni-, Mn-, and Mo-anchored TiO2. This concept offers an avenue for elaborate design of green, robust, and pH-universal cathodic Fenton-like catalysts and beyond.

The model for predicting the central lymph node metastasis in cN0 papillary thyroid microcarcinoma with Hashimoto's thyroiditis.

Background: The relationship between Hashimoto's thyroiditis (HT) and papillary thyroid microcarcinoma (PTMC) is controversial. These include central lymph node metastasis (CLNM), which affects the prognosis of PTMC patients. This study aimed to establish a predictive model combining ultrasonography and clinicopathological features to accurately evaluate latent CLNM in PTMC patients with HT at the clinical lymph node-negative (cN0) stage. Methods: In this study, 1102 PTMC patients who received thyroidectomy and central cervical lymph node dissection (CLND) from the First Affiliated Hospital of Shandong First Medical University from January 2021 to December 2022 and the 960th Hospital of PLA from January 2021 to December 2022 were jointly collected. The clinical differences between PTMCs with HT and those without HT were compared. A total of 373 PTMCs with HT in cN0 were randomly divided into a training cohort and a validation cohort. By analyzing and screening the risk factors of CLNM, a nomogram model was established and verified. The predictive performance was measured by the receiver operating characteristic (ROC) curve, calibration curve, and clinical decision curve analysis (DCA). Results: The ratio of central lymph node metastasis (CLNMR) in PTMCs with HT was 0.0% (0.0%, 15.0%) and 7.7% (0.0%, 40.0%) in the non-HT group (P<0.001). Multivariate logistic regression analysis showed that age, gender, calcification, adjacent to trachea or capsule, and TPOAB were predictors of CLNM in PTMCs with HT. The areas under the curve (AUC) of the prediction models in the training cohort and the validation cohort were 0.835 and 0.825, respectively, which showed good differentiation ability. DCA indicates that the prediction model also has high net benefit and clinical practical value. Conclusion: This study found that CLN involvement was significantly reduced in PTMC patients with HT, suggesting that different methods should be used to predict CLNM in PTMC patients with HT and without HT, to more accurately assist preoperative clinical evaluation. The actual CLNM situation of PTMCs with HT in cN0 can be accurately predicted by the combination of ultrasonography and clinicopathological features.

Lateral habenula 5-HT1B receptors are involved in regulation of anxiety-like behaviors in parkinsonian rats.

Although the output of the lateral habenula (LHb) controls the activity of midbrain dopaminergic and serotonergic systems, which are implicated in the pathophysiology of anxiety, it is not clear the role of LHb 5-HT1B receptors in regulation of anxiety-like behaviors, particularly in Parkinson's disease-related anxiety. In this study, unilateral 6-hydroxydopamine lesions of the substantia nigra pars compacta in rats induced anxiety-like behaviors, led to decreased normalized δ power and increased normalized θ power in the LHb, and decreased dopamine (DA) level in the prelimbic cortex (PrL) compared with sham rats. Down-regulation of LHb 5-HT1B receptors by RNA interference produced anxiety-like effects, decreased normalized δ power and increased normalized θ power in the LHb in both sham and lesioned rats. Further, intra-LHb injection of 5-HT1B receptor agonist CP93129 induced anxiolytic-like responses, increased normalized δ power and decreased normalized θ power in the LHb, and increased DA and serotonin (5-HT) release in the PrL; conversely, 5-HT1B receptor antagonist SB216641 produced anxiety-like effects, decreased normalized δ power and increased normalized θ power in the LHb, and decreased DA and 5-HT release in the PrL in sham and lesioned rats. Additionally, effects of CP93129 and SB216641 on the behaviors, normalized δ and θ power in the LHb, and DA and 5-HT release in the PrL were decreased in lesioned rats, which were consistent with down-regulation of LHb 5-HT1B receptors after DA depletion. Collectively, these findings suggest that 5-HT1B receptors in the LHb are involved in the regulation of anxiety-like behaviors.

Menstrual abnormalities effects on clinical features and in vitro fertilization pregnancy outcomes in women with polycystic ovarian syndrome.

BACKGROUND: The diagnostic criteria and phenotypes in polycystic ovary syndrome are heterogeneous. Currently, it is unclear how to assess a patient's prognosis based on the onset time of menstruation disturbance. Evidence on this topic is scarce and has mainly focused on menstrual patterns. OBJECTIVE: This study aimed to assess the association between the onset time of menstrual disturbance and clinical features and in vitro fertilization pregnancy outcomes in patients with polycystic ovary syndrome. STUDY DESIGN: Our study was a secondary analysis of data collected as part of a randomized controlled trial conducted to compare live birth rates between fresh embryo transfer and frozen embryo transfer in 1508 individuals with polycystic ovary syndrome. Here, 1500 participants were classified into 2 groups according to the onset time of menstrual disturbance: immediately after menarche (early group) and after at least 1 year of regular menstruation (late group). We compared the prepregnancy clinical features, variables of ovarian stimulation, pregnancy outcomes after the initial cycle of embryo transfer, and perinatal and neonatal complications in the 2 groups. RESULTS: Compared with the late group, the early group had more antral follicles (32.00 [range, 27.25-39.50] vs 28.00 [range, 24.00-36.00]; P<.001), an elevated level of antimüllerian hormone (7.02 ng/mL [range, 3.60-11.47] vs 5.66 ng/mL [range, 3.65-8.92]; P=.024), a higher level of baseline luteinizing hormone (10.01±5.93 vs 8.51±5.53 IU/l; P<.001) and luteinizing hormone-to-follicle-stimulating hormone ratio (1.51 [range, 1.00-2.32] vs 1.45 [range, 0.92-2.13]; P<.001), lower levels of fasting glucose (5.47 mmol/L [range, 5.11-5.73] vs 5.50 mmol/L [range, 5.17-5.76]; P<.001), and insulin at 2 hours after 75-g oral glucose tolerance test (56.85 µU/mL [range, 34.63-94.54] vs 59.82 µU/mL [range, 33.56-94.67]; P=.027), a higher level of high-density lipoprotein (1.26 mmol/L [range, 1.04-1.37] vs 1.21 mmol/L [range, 1.07-1.45]; P=.006). During in vitro fertilization, the early group had a higher level of peak estradiol (4596.50 pg/mL [range, 2639.25-6321.00] vs 3954.00 pg/mL [range, 2378.75-6113.50]; P=.013), and luteinizing hormone (2.52 IU/L [range, 1.40-4.21] vs 1.93 IU/L [range, 0.91-3.32]; P=.010) on the day of human chorionic gonadotropin trigger. There was no statistically significant difference observed in the number of oocytes and embryos, the rates of pregnancy and live birth, and the risks of obstetrical and neonatal between the 2 groups. CONCLUSION: An early onset of menstrual disturbance in patients with polycystic ovary syndrome may be associated with slightly more severe reproductive features and slightly milder metabolic features. Nonetheless, the outcomes of in vitro fertilization and the initial cycle of embryo transfer were comparable between the 2 groups.

The difference in early trimester fetal growth between singletons after frozen embryo transfer and fresh embryo transfer.

BACKGROUND: Frozen embryo transfer resulted in a higher birthweight and an increased risk of macrosomia than fresh embryo transfer. However, the mechanism was still unclear. When the impact of frozen embryo transfer on fetal growth began was unknown. Crown-rump length at 11-13 weeks had been regarded as a good indicator of fetal growth in the first trimester and had been used for gestational age calculation in women with uncertain last menstrual periods. OBJECTIVE: To evaluate the association between frozen embryo transfer and early fetal growth, particularly the crown-rump length, then fresh embryo transfer. The secondary objective was to investigate the potential correlation between crown-rump length and birthweight. STUDY DESIGN: This was a retrospective cohort study conducted at the Reproductive Medical Center of Shandong University. A total of 4949 patients who obtained singleton pregnancy after frozen embryo transfer and 1793 patients who got singleton pregnancy after fresh embryo transfer between January 1, 2017 and December 31, 2022 were included. The primary outcome was the crown-rump length measured via ultrasound at 11-13 weeks gestation. The secondary outcomes were perinatal outcomes, including birthweight and the risk of large for gestational age, small for gestational age, macrosomia, low birthweight, and premature delivery. Multivariable linear regression models were used to adjust for potential confounders of crown-rump length. RESULTS: A total of 6742 live singleton births after frozen embryo transfer or fresh embryo transfer were included in this study. In the univariable analysis, the frozen embryo transfer group had a larger crown-rump length (5.75±0.53 cm vs 5.57±0.48 cm, P<.001) and an increased risk of larger-than-expected crown-rump length (13.5% vs11.2%, P=.013) than the fresh embryo transfer group. After adjusting for confounders in multivariable linear regression models, frozen embryo transfer was still associated with a larger crown-rump length (regression coefficient, 3.809 [95% confidence intervals, 3.621-3.997], P<.001). When subgrouped by fetal gender, the crown-rump length of the frozen embryo transfer group was larger than the fresh embryo transfer group in both male and female fetuses. In addition, the crown-rump length was consistently larger in the frozen embryo transfer group than the fresh embryo transfer group in subgroups of the peak estradiol levels. The comparisons among different crown-rump length groups showed that smaller-than-expected crown-rump length was associated with increased risks of small for gestational age (6.3% vs 3.0%, P<.001) and preterm delivery (9.6% vs 6.7%, P=.004) than normal crown-rump length. CONCLUSION: Frozen embryo transfer was associated with a larger crown-rump length than fresh embryo transfer, suggesting that the effect of frozen embryo transfer on fetal growth may begin in the early trimester. Suboptimal fetal growth in the first trimester may be associated with low birthweight and premature delivery.

Bone marrow stromal cells dictate lanosterol biosynthesis and ferroptosis of multiple myeloma.

Ferroptosis has been demonstrated a promising way to counteract chemoresistance of multiple myeloma (MM), however, roles and mechanism of bone marrow stromal cells (BMSCs) in regulating ferroptosis of MM cells remain elusive. Here, we uncovered that MM cells were more susceptible to ferroptotic induction under the interaction of BMSCs using in vitro and in vivo models. Mechanistically, BMSCs elevated the iron level in MM cells, thereby activating the steroid biosynthesis pathway, especially the production of lanosterol, a major source of reactive oxygen species (ROS) in MM cells. We discovered that direct coupling of CD40 ligand and CD40 receptor constituted the key signaling pathway governing lanosterol biosynthesis, and disruption of CD40/CD40L interaction using an anti-CD40 neutralizing antibody or conditional depletion of Cd40l in BMSCs successfully eliminated the iron level and lanosterol production of MM cells localized in the Vk*MYC Vk12653 or NSG mouse models. Our study deciphers the mechanism of BMSCs dictating ferroptosis of MM cells and highlights the therapeutic potential of non-apoptosis strategies for managing refractory or relapsed MM patients.

Automated extraction of Tridacna shell growth patterns via machine learning for enhanced paleoclimate/paleoweather research.

Tridacna spp. are valuable archives for paleoclimate and paleoweather research due to their distinct daily growth patterns and the sensitivity of the daily growth patterns to environment changes. However, manually identifying daily growth lines and measuring the daily growth increment width (DGIW) of Tridacna shells from Laser Scanning Confocal Microscopy (LSCM) images is a tedious task that has become a significant barrier to Tridacna studies. This paper addresses this challenge by integrating machine learning into Tridacna research for the first time to automate the calculation of the number of daily growth lines and DGIW of Tridacna shells. Specifically, we propose an unsupervised generative adversarial attention network called TriGAN to automatically recognize distinct daily growth lines of Tridacna shells from LSCM images. Utilizing modern Tridacna specimens collected from the South China Sea, our experimental results demonstrate that TriGAN can effectively reconstruct the ambiguous and blurred regions in LSCM images and produce higher quality images of daily growth patterns compared to existing image generation networks. Furthermore, the daily growth line number and DGIW of Tridacna shells can be counted automatically from the images recognized by TriGAN, which are in good agreement with the statistical results obtained manually from the original LSCM images (R = 0.7, p < 0.01 for the DGIW profile of T. gigas specimen MD1 and R = 0.6, p < 0.01 for T. derasa specimen XB10). This automated method provides an efficient solution for researching the laminar chronology of Tridacna.

CaMK4: Structure, physiological functions, and therapeutic potential.

Calcium/calmodulin-dependent protein kinase IV (CaMK4) is a versatile serine/threonine kinase involved in various cellular functions. It regulates T-cell differentiation, podocyte function, tumor cell proliferation/apoptosis, ß cell mass, and insulin sensitivity. However, the underlying molecular mechanisms are complex and remain incompletely understood. The aims of this review are to highlight the latest advances in the regulatory mechanisms of CaMK4 underlying T-cell imbalance and parenchymal cell mass in multiple diseases. The structural motifs and activation of CaMK4, as well as the potential role of CaMK4 as a novel therapeutic target are also discussed.