Associations between circulating proteins and cardiometabolic diseases: a systematic review and meta-analysis of observational and Mendelian randomisation studies.

BACKGROUND: Integration of large proteomics and genetic data in population-based studies can provide insights into discovery of novel biomarkers and potential therapeutic targets for cardiometabolic diseases (CMD). We aimed to synthesise existing evidence on the observational and genetic associations between circulating proteins and CMD. METHODS: PubMed, Embase and Web of Science were searched until July 2023 for potentially relevant prospective observational and Mendelian randomisation (MR) studies investigating associations between circulating proteins and CMD, including coronary heart disease, stroke, type 2 diabetes, heart failure, atrial fibrillation and atherosclerosis. Two investigators independently extracted study characteristics using a standard form and pooled data using random effects models. RESULTS: 50 observational, 25 MR and 10 studies performing both analyses were included, involving 26 414 160 non-overlapping participants. Meta-analysis of observational studies revealed 560 proteins associated with CMD, of which 133 proteins were associated with ≥2 CMDs (ie, pleiotropic). There were 245 potentially causal protein biomarkers identified in MR pooled results, involving 23 pleiotropic proteins. IL6RA and MMP12 were each causally associated with seven diseases. 22 protein-disease pairs showed directionally concordant associations in observational and MR pooled estimates. Addition of protein biomarkers to traditional clinical models modestly improved the accuracy of predicting incident CMD, with the highest improvement for heart failure (ΔC-index ~0.2). Of the 245 potentially causal proteins (291 protein-disease pairs), 3 pairs were validated by evidence of drug development from existing drug databases, 288 pairs lacked evidence of drug development and 66 proteins were drug targets approved for other indications. CONCLUSIONS: Combined analyses of observational and genetic studies revealed the potential causal role of several proteins in the aetiology of CMD. Novel protein biomarkers are promising targets for drug development and risk stratification. PROSPERO REGISTRATION NUMBER: CRD42022350327.

Value of 2D ultrasonography in the diagnosis and evaluation of intrauterine adhesions - a prospective study.

RESEARCH QUESTION: What is the value of 2D ultrasonography in the diagnosis and assessment of intrauterine adhesions (IUA)? DESIGN: This was a prospective study conducted at a hysteroscopy centre. RESULTS: Of a total of 600 subjects recruited, 41 dropped out and 559 were finally enrolled and analysed. The observed 2D ultrasonography features, in decreasing order of frequency, were 'irregular endometrium' (37.9%), 'broken endometrial echo' (23.4%), 'thin endometrium' (13.7%), 'loss of endometrial echo' (13.1%,), 'hyperechoic focus' (12.5%) and 'fluid in the cavity' (8.8%). The sensitivity of individual ultrasound features ranged from 8.8% to 37.9%, whereas the specificity of individual ultrasound features ranged from 78.9% to 100%. When all the six ultrasound features were considered together, the sensitivity and specificity were 71.7% and 66.2% respectively. The sensitivity, specificity and accuracy of ultrasound diagnosis in the mid-proliferative phase, peri-ovulatory phase and mid-luteal phase did not appear to be significantly different statistically, although the results in the mid-proliferative phase appeared to be consistently higher than those in the mid-luteal phase. In women confirmed to have IUA, the likelihood of the adhesions being severe in nature in the presence of zero, one, two or three or more ultrasound features was 8.7%, 23.0%, 40.2% and 80.5%, respectively (P < 0.001). CONCLUSIONS: The findings in this study support the notions that ultrasonography examination in women suspected to have IUA cannot replace hysteroscopy in the diagnosis of the condition. However, it does provide useful clinical information regarding severity and could help in the planning of hysteroscopy to optimize management.

Clinical analysis of diabetes in pregnancy with stillbirth.

We analyzed the clinical characteristics of patients with diabetes in pregnancy (DIP) associated with stillbirth and explored strategies to reduce its incidence. We retrospectively analyzed 71 stillbirths associated with DIP (group A) and 150 normal pregnancies (group B) during 2009 to 2018. The incidence of the following was higher in group A (P < .05): hypertensive disorders (38.03% vs 6.00%), placenta previa (14.08% vs 2.67%), placental abruption (5.63% vs 0.67%), fetal malformation (8.45% vs 0.67%), fasting plasma glucose (FPG) ≥ 7.0 mmol/L (46.48% vs 0.67%), 2-h postprandial plasma glucose ≥ 11.1 mmol/L (57.75% vs 6.00%), HbA1c ≥ 6.5% (63.38% vs 6.00%), and polyhydramnios (11.27% vs 4.67). The incidence of oligohydramnios (4.23% vs 6.67%) was lower in group A than in group B (P < .05). According to the gestational age at the time of stillbirth, Group-A cases were subgrouped into miscarriages (20-27+6 weeks), premature deliveries (28-36+6 weeks), and full-term deliveries (≥37 weeks). Age, parity, and DIP type did not differ among the subgroups (P > .05). Among patients with DIP, antenatal FPG, 2-h postprandial plasma glucose, and HbA1c were significantly associated with stillbirth (P < .05). Stillbirth was first detected at 22 weeks and typically occurred at 28-36+6 weeks. DIP was associated with a higher incidence of stillbirth, and FPG, 2-h postprandial plasma glucose, and HbA1c were potential indicators of stillbirth in DIP. Age (odds ratio [OR]: 2.21, 95% confidence interval [CI]: 1.67-2.74), gestational hypertension (OR: 3.44, 95% CI: 2.21-4.67), body mass index (OR: 2.86, 95% CI: 1.95-3.76), preeclampsia (OR: 2.29, 95% CI: 1.45-3.12), and diabetic ketoacidosis (OR: 3.99, 95% CI: 1.22-6.76) were positively correlated with the occurrence of stillbirth in DIP. Controlling perinatal plasma glucose, accurately detecting and managing comorbidities/complications, and timely termination of pregnancy can reduce the incidence of stillbirths associated with DIP.

Large-Area Black Phosphorus/PtSe2 Schottky Junction for High Operating Temperature Broadband Photodetectors.

High operating temperature (HOT) broadband photodetectors are urgently necessary for extreme condition applications in infrared-guided missiles, infrared night vision, fire safety imaging, and space exploration sensing. However, conventional photodetectors show dramatic carrier mobility decreases and carrier losses with low photoresponsivity at HOT due to the increased carrier scattering in channels at high temperatures. Herein, the HOT broadband photodetectors from room temperature to 470 K are developed for the first time by large-area black phosphorus (BP)/PtSe2 films device arrays via a depletion-enhanced photocarrier dynamics strategy. Attributed to the 2D Schottky junction at BP/PtSe2 interface and resulting in full depleted working channels, the BP/PtSe2 photodetector arrays exhibit high tolerance to carrier mobility decrease during the increasing operating temperature in a wide wavelength range from 532 to 2200 nm. Thus, the photodetector shows a state-of-the-art operating temperature at 470 K with the photo-responsivity (R) and specific detectivity (D*) of 25 A W-1 and 6.4 × 1011 Jones under 1850 nm illumination, respectively. Moreover, BP/PtSe2 photodetector arrays show high-uniformity photo-response in a large area. This work provides new strategies for high-performance broadband photodetector arrays with HOT by Schottky junction of large-area BP/PtSe2 films.

Water-responsive gel extends drug retention and facilitates skin penetration for curcumin topical delivery against psoriasis.

Psoriasis is a chronic inflammatory skin disease characterized by erythema, scaling, and skin thickening. Topical drug application is recommended as the first-line treatment. Many formulation strategies have been developed and explored for enhanced topical psoriasis treatment. However, these preparations usually have low viscosity and limited retention on the skin surface, resulting in low drug delivery efficiency and poor patient satisfaction. In this study, we developed the first water-responsive gel (WRG), which has a distinct water-triggered liquid-to-gel phase transition property. Specifically, WRG was kept in a solution state in the absence of water, and the addition of water induced an immediate phase transition and resulted in a high viscosity gel. Curcumin was used as a model drug to investigate the potential of WRG in topical drug delivery against psoriasis. In vitro and in vivo data showed that WRG formulation could not only extend skin retention but also facilitate the drug permeating across the skin. In a mouse model of psoriasis, curcumin loaded WRG (CUR-WRG) effectively ameliorated the symptoms of psoriasis and exerted a potent anti-psoriasis effect by extending drug retention and facilitating drug penetration. Further mechanism study demonstrated that the anti-hyperplasia, anti-inflammation, anti-angiogenesis, anti-oxidation, and immunomodulation properties of curcumin were amplified by enhanced topical drug delivery efficiency. Notably, neglectable local or systemic toxicity was observed for CUR-WRG application. This study suggests that WRG is a promising formulation for topically psoriasis treatment.

Effects of glucose and osmotic pressure on the proliferation and cell cycle of human chorionic trophoblast cells.

This study investigated the effects of glucose and osmotic pressure on the proliferation and cell cycle of trophoblast cells. HTR8/SVneo cells were treated with 0 (no glucose), 1 (low glucose), 5 (normal), and 25 mmol/L (high glucose) glucose. In addition, the cells were treated with 5 mmol/L glucose (normal) and 5 mmol/L glucose + 20 mmol/L mannitol (mannitol). The cell morphology and proliferation were determined by microscopy and a cell counting kit-8 assay. The cell cycle and apoptosis were examined by flow cytometry. The cell number was relatively decreased and morphological changes were intermediate in the high-glucose group compared with the low-glucose groups. The proportion of cells in the G2/M phase was higher in the low-glucose group than in the other groups, and it was lower in the G1 phase and higher in the S phase in the high-glucose group than in the other groups. Compared with 24 h, cell proliferative activity was restored to a certain extent after 48 h in the high-glucose group. In summary, the blood glucose concentration might influence the proliferation of trophoblast cells. A high-glucose environment inhibited initial cell proliferation, which could be moderately restored after self-regulation. Furthermore, the proliferation of trophoblasts was not affected by the osmotic pressure.

Clinical analysis of 2860 cases of diabetes in pregnancy: a single-center retrospective study.

BACKGROUND: To investigate the epidemiological, clinical characteristics and outcomes of diabetes in pregnancy (DIP). METHODS: This single-center, retrospective study included 16,974 pregnant women hospitalized during 2018-2019. Among them, 2860 DIP patients were grouped according to diabetes type, glycemic status, and insulin use. Multivariate logistic regression analysis was conducted. RESULTS: The incidence of DIP [17.10%; pregestational diabetes mellitus (PGDM), 2.00% (type I, 0.08%; type 2, 1.92%); gestational diabetes mellitus (GDM), 14.85% (GDM A1, 13.58%; GDM A2, 1.27%)] increased annually. Premature birth, congenital anomalies, large for gestational age (LGA), neonatal asphyxia, neonatal intensive care unit transfer, hypertension, and puerperal infection were more common in DIP than in healthy pregnancies. The most common comorbidities/complications were hypertension, thyroid dysfunction, cervical incompetence, intrahepatic cholestasis, premature membrane rupture, oligo/polyhydramnios, and fetal distress. GDM incidence at ages ≥35 and ≥ 45 years was 1.91 and 3.26 times that at age < 35 years, respectively. If only women with high-risk factors were screened, 34.8% GDM cases would be missed. The proportion of insulin use was 14.06% (PGDM, 55%; GDM, 8.53%). Mean gestational age at peak insulin dose in DIP was 32.87 ± 5.46 weeks. Peak insulin doses in PGDM and GDM were 3.67 and 2 times the initial doses, respectively. The risks of LGA, premature birth, cesarean section, and neonatal hypoglycemia in PGDM were 1.845, 1.533, 1.797, and 1.368 times of those in GDM, respectively. The risks of premature birth and neonatal hypoglycemia in women with poor glycemic control were 1.504 and 1.558 times of those in women with good control, respectively. CONCLUSIONS: The incidence of adverse outcomes in DIP is high.

Opsonized nanoparticles target and regulate macrophage polarization for osteoarthritis therapy: A trapping strategy.

Osteoarthritis (OA) is a chronic disease caused by joint inflammation. Its occurrence and development depend on a continuous inflammation environment. The activated M1 macrophages play a critical role in the inflammatory response of OA. Regulating the pro-inflammatory M1 to anti-inflammatory M2 macrophages in the OA articular cavity could be a rational strategy for OA treatment. It has been acknowledged that activated macrophages could proactively capture opsonized nanoparticles in the bloodstream and then accumulate into the reticuloendothelial system (RES) organs. Based on this fact, a trapping strategy is proposed, which transforms a normal nanoparticle into an opsonized attractant to target and regulate macrophage polarization. In this study, the opsonized nanoparticle (IgG/Bb@BRPL) had several key features, including an immunoglobulin IgG (the opsonized layer), an anti-inflammatory agent berberine (Bb), and an oxidative stress-responsive bilirubin grafted polylysine biomaterial (BR-PLL) for drug loading (the inner nanocore). In vitro studies confirmed that IgG/Bb@BRPL prefer to be phagocytosed by M1 macrophage, not M0. And the internalized IgG/Bb@BRPL effectively promoted macrophage polarization toward the M2 phenotype and protected nearby chondrocytes. In vivo studies suggested that IgG/Bb@BRPL significantly enhanced therapeutic outcomes by suppressing inflammation and promoting cartilage repair while not prolonging the retention period compared to non-opsonized counterparts. This proof-of-concept study provided a novel opsonization trapping strategy for OA drug delivery and treatment.

An Ionically Conductive, Self-Powered and Stable Organogel for Pressure Sensing.

Gel-based ionic conductors are promising candidates for flexible electronics, serving as stretchable sensors or electrodes. However, most of them suffer from a short operating life, low conductivity and rely on an external power supply, limiting their practical application. Herein, we report a stable organogel ionic conductor with high conductivity and self-powering ability. Briefly, lithium trifluoromethanesulfonate, as a conductive salt, provides high conductivity and the poly(1,1-difluoroethylene) layers, as a self-powering system, supply stable energy output under the influence of pressure. Moreover, the proposed conductors withstand long-term and multi-cycle durability tests. The prepared auxiliary training device can withstand the impact of a basketball and detect the impact force, showing potential in passive sensing during practical applications.

Relationship of Amniotic Fluid Sludge and Short Cervix With a High Rate of Preterm Birth in Women After Cervical Cerclage.

OBJECTIVE: We aims to determine the relationship of amniotic fluid sludge (AFS) and/or short cervical length (CL, ≤25 mm) with a high rate of preterm birth in women after cervical cerclage. METHODS: A retrospective cohort study was conducted among singleton pregnancies after cervical cerclage between January 2018 and December 2021. A total of 296 patients who underwent transvaginal ultrasound to evaluate CL and the presence of AFS within 2 weeks after cerclage were included. Pregnancy outcome after cerclage was analyzed in accordance with the presence of AFS and CL ≤25 mm. RESULTS: In patients with cerclage, AFS was an independent risk factor for preterm birth at <28 and <36 weeks but not for preterm birth at <32 weeks, and CL ≤25 mm was an independent risk factor for preterm birth at <28, <32, and <36 weeks. The Kaplan-Meier analysis showed that the association between the presence of AFS and short gestational age at delivery was statistically significant in women with CL ≤25 mm (log rank test, P = .000). The Cox regression analysis showed that these results remained significant after adjusting for confounding factors (P = .000). The negative linear relationships between AFS and CL (R = -0.454, P < .001) also explained the outcome. CONCLUSIONS: AFS and short cervix have a direct effect on pregnancies after cerclage. Mid-trimester AFS can become a supplementary ultrasound index for detecting preterm birth after cerclage in pregnant women with a short cervix.

Resetting amino acid metabolism of cancer cells by ATB0,+-targeted nanoparticles for enhanced anticancer therapy.

Reprogramed cellular metabolism is one of the most significant hallmarks of cancer. All cancer cells exhibit increased demand for specific amino acids, and become dependent on either an exogenous supply or upregulated de novo synthesis. The resultant enhanced availability of amino acids supports the reprogramed metabolic pathways and fuels the malignant growth and metastasis of cancers by providing energy and critical metabolic intermediates, facilitating anabolism, and activating signaling networks related to cell proliferation and growth. Therefore, pharmacologic blockade of amino acid entry into cancer cells is likely to have a detrimental effect on cancer cell growth. Here we developed a nanoplatform (LJ@Trp-NPs) to therapeutically target two transporters, SLC6A14 (ATB0,+) and SLC7A5 (LAT1), that are known to be essential for the sustenance of amino acid metabolism in most cancers. The LJ@Trp-NPs uses tryptophan to guide SLC6A14-targeted delivery of JPH203, a high-affinity inhibitor of SLC7A5. In the process, SLC6A14 is also down-regulated. We tested the ability of this strategy to synergize with the anticancer efficacy of lapatinib, an inhibitor of EGFR/HER1/HER2-assocated kinase. These studies show that blockade of amino acid entry amplifies the anticancer effect of lapatinib via interference with mTOR signaling, promotion of apoptosis, and suppression of cell proliferation and metastasis. This represents the first study to evaluate the impact of amino acid starvation on the anticancer efficacy of widely used kinase inhibitor.

MXenes for Solar Cells.

Application of two-dimensional MXene materials in photovoltaics has attracted increasing attention since the first report in 2018 due to their metallic electrical conductivity, high carrier mobility, excellent transparency, tunable work function and superior mechanical property. In this review, all developments and applications of the Ti3C2Tx MXene (here, it is noteworthy that there are still no reports on other MXenes' application in photovoltaics by far) as additive, electrode and hole/electron transport layer in solar cells are detailedly summarized, and meanwhile, the problems existing in the related studies are also discussed. In view of these problems, some suggestions are given for pushing exploration of the MXenes' application in solar cells. It is believed that this review can provide a comprehensive and deep understanding into the research status and, moreover, helps widen a new situation for the study of MXenes in photovoltaics.

Association of gestational diabetes mellitus with changes in gut microbiota composition at the species level.

BACKGROUND: Gestational diabetes mellitus (GDM), a common endocrine disorder with rising prevalence in pregnancy, has been reported to be associated with alteration of gut microbiota in recent years. However, the role of gut microbiome in GDM physiopathology remains unclear. This pilot study aims to characterize the alteration of gut microbiota in GDM on species-level resolution and evaluate the relationship with occurrence of GDM. METHODS: An analysis based on 16S rRNA microarray was performed on fecal samples obtained from 30 women with GDM and 28 healthy pregnant women. RESULTS: We found 54 and 141 differentially abundant taxa between GDM and control group at the genus and the species level respectively. Among GDM patients, Peptostreptococcus anaerobius was inversely correlated with fasting glucose while certain species (e.g., Aureimonas altamirensis, Kosakonia cowanii) were positively correlated with fasting glucose. CONCLUSIONS: This study suggests that there are large amounts of differentially abundant taxa between GDM and control group at the genus and the species level. Some of these taxa were correlated with blood glucose level and might be used as biomarkers for diagnoses and therapeutic targets for probiotics or synbiotics.

Bienenstock-Cooper-Munro Learning Rule Realized in Polysaccharide-Gated Synaptic Transistors with Tunable Threshold.

With reference to the organization of the human brain nervous system, a hardware-based approach that builds massively parallel neuromorphic circuits is of great significance to neuromorphic computing. The Bienenstock-Cooper-Munro (BCM) learning rule, which describes that the synaptic weight modulation exhibits frequency-dependent and tunable frequency threshold characteristics, is more compatible with the working principle of neuromorphic computing systems than spike-timing-dependent plasticity. Therefore, it is interesting to simulate the BCM learning rule on solid-state synaptic devices. Here, we have prepared λ-carrageenan (λ-car) electrolyte-gated oxide synaptic transistors, which exhibit good transistor performances, including a low subthreshold swing of 125 mV/dec, an on/off ratio larger than 106, and a mobility of 9.5 cm2 V-1 s-1. By modulating the initial channel current and spike frequency, the simulation of the BCM rule was successfully realized. The competitive relationship between the drift of protons under an electric field and the spontaneous diffusion of protons can explain this mechanism. The proposed λ-car-gated synaptic transistor has a great significance to neuromorphic computing.

Publisher Correction: A Unified Framework for Complex Networks with Degree Trichotomy Based on Markov Chains.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Independently tunable double Fano resonances based on waveguide-coupled cavities.

In this Letter, we first demonstrate periodically and independently tunable double Fano resonances (DFRs) using waveguide-coupled cavities consisting of two silicon microring resonators (MRRs) and a feedback-coupled waveguide. The proposed device is fabricated on the silicon-on-insulator substrate using the standard complementary metal-oxide-semiconductor fabrication process. The DFR can be tuned independently by changing the resonant wavelengths of two MRRs using the thermo-optic effect. The highest extinction ratio of the Fano resonances is measured to be as high as 29.20 dB, which enables this device to be a promising candidate for high-performance multi-wavelength optical switches and high-sensitivity biochemical sensors.

The interaction between estradiol change and the serotonin transporter gene (5-HTTLPR) polymorphism is associated with postpartum depressive symptoms.

Although estrogenic fluctuation is considered a major risk factor for postpartum depression (PPD), the effects of the interactions between the genetic background and estradiol (E2) change on PPD are not well understood. Here, a cohort study with 437 postpartum women was carried out to evaluate the role of a serotonin transporter gene polymorphism (5-HTTLPR) and E2 change on the risk of PPD symptoms. The participants were assessed using the Edinburgh Postnatal Depression Scale and the Self-Rating Depression Scale at 1 and 6 weeks after delivery. The PCR-based restriction fragment length polymorphism method was utilized to examine the genotype distribution of the 5-HTTLPR polymorphism, and the serum levels of E2 were determined in individuals in the third trimester of pregnancy and at 1 week postpartum. A significant association was observed between E2 change and PPD susceptibility in the late postpartum period (6 weeks) [P = 0.002, odds ratio (OR) = 2.341, 95% confidence interval (CI) = 1.361-4.027], but it was not observed in the early postpartum period (1 week). There was no significant association between the 5-HTTLPR genotype and PPD risk at both the early and late postpartum periods (P > 0.05). However, the interaction between E2 change and the 5-HTTLPR polymorphism could reasonably influence PPD risk. The women who carried the SS genotype with large decreases in E2 showed a significantly higher risk for PPD at both the early (P = 0.002, OR = 2.525, 95% CI = 1.384-4.059) and late postpartum periods (P < 0.001, OR = 3.108, 95% CI = 1.562-4.436) compared with those who carried the SL/LL genotype. This study suggests that there is an association between E2 change in the perinatal period with the 5-HTTLPR genotype and the occurrence of PPD.

Primary cardiac lymphoma in both atria: A case report.

Primary cardiac lymphoma (PCL) is a very rare kind of primary heart tumor, belonging to non-Hodgkin's lymphoma whose major pathological type is diffuse large B-cell lymphoma. The common symptoms include heart failure, pericardial effusion, and malignant arrhythmias. Early diagnosis and treatment of PCL are of great importance due to its merely 7-month median survival period. Here, we report a 48-year-old male patient in whom both atria were involved and had to undergo palliative surgery because of severe clinical symptoms.

Retinoids, anxiety and peripartum depressive symptoms among Chinese women: a prospective cohort study.

BACKGROUND: The current study aimed to investigate whether serum RBP levels can be a key predictor of peripartum depression (PPD). METHODS: This was a prospective cohort study, conducted at a general teaching hospital in South China. Research participants were evaluated at three time points: the third trimester of pregnancy (T1), after delivery at week one (T2), and after delivery week six (T3) using a set of self-reported questionnaires and blood sample assays. RESULTS: A total of 156 subjects were included for data analysis. The prevalence of anxiety symptoms ranged from 32.69% to 36.53%. The prevalence of PPD was also high and ranged from 27.56% to 35.89%. In the third trimester, significant predictors of depressive symptoms include serum retinol-binding protein (RBP) concentrations and estradiol levels (P = 0.008 and 0.033, respectively). At one week after delivery, serum concentrations of RBP at T2 were still significant predictors of depressive symptoms (P = 0.020, and serum estradiol concentrations at T1 were a significant predictor (P = 0.010). The most stable predictor of depressive symptoms at T3 was anxiety symptoms, especially at T3 time point (P < 0.001). Serum RBP concentrations at T1 and T2 were still significant predictors of depressive symptoms at T3. CONCLUSION: A high prevalence of anxiety and depressive symptoms tended to persist in Chinese women during the peripartum period. This study, which found the potential contribution of RBP to the occurrence of PPD, requires that large sample studies be conducted in future with a longer-term follow-up period, in order to confirm its results.