Fetal overgrowth and weight trajectories during infancy and adiposity in early childhood.

BACKGROUND: Large-for-gestational age (LGA), a marker of fetal overgrowth, has been linked to obesity in adulthood. Little is known about how infancy growth trajectories affect adiposity in early childhood in LGA. METHODS: In the Shanghai Birth Cohort, we followed up 259 LGA (birth weight >90th percentile) and 1673 appropriate-for-gestational age (AGA, 10th-90th percentiles) children on body composition (by InBody 770) at age 4 years. Adiposity outcomes include body fat mass (BFM), percent body fat (PBF), body mass index (BMI), overweight/obesity, and high adiposity (PBF >85th percentile). RESULTS: Three weight growth trajectories (low, mid, and high) during infancy (0-2 years) were identified in AGA and LGA subjects separately. BFM, PBF and BMI were progressively higher from low- to mid-to high-growth trajectories in both AGA and LGA children. Compared to the mid-growth trajectory, the high-growth trajectory was associated with greater increases in BFM and the odds of overweight/obesity or high adiposity in LGA than in AGA children (tests for interactions, all P < 0.05). CONCLUSIONS: Weight trajectories during infancy affect adiposity in early childhood regardless of LGA or not. The study is the first to demonstrate that high-growth weight trajectory during infancy has a greater impact on adiposity in early childhood in LGA than in AGA subjects. IMPACT: Large-for-gestational age (LGA), a marker of fetal overgrowth, has been linked to obesity in adulthood, but little is known about how weight trajectories during infancy affect adiposity during early childhood in LGA subjects. The study is the first to demonstrate a greater impact of high-growth weight trajectory during infancy (0-2 years) on adiposity in early childhood (at age 4 years) in subjects with fetal overgrowth (LGA) than in those with normal birth size (appropriate-for-gestational age). Weight trajectory monitoring may be a valuable tool in identifying high-risk LGA children for close follow-ups and interventions to decrease the risk of obesity.

Nanoplastic Exposure at Environmental Concentrations Disrupts Hepatic Lipid Metabolism through Oxidative Stress Induction and Endoplasmic Reticulum Homeostasis Perturbation.

In this study, we investigated the mechanism underlying the perturbation of hepatic lipid metabolism in response to micro/nanoplastic (MP/NP) exposure at environmentally relevant concentrations. Polystyrene (PS) MPs/NPs with different sizes (0.1, 0.5, and 5.0 µm) were studied for their effects on the homeostasis and function of Nile tilapia (Oreochromis niloticus) liver. Results showed that PS MPs/NPs were readily internalized and accumulated in various internal organs/tissues, especially in fish liver and muscle. Smaller-sized NPs caused more severe toxicity than larger MPs, including hepatic steatosis, inflammatory response, and disturbed liver function. Mechanistically, PS NPs with a particle size of 100 nm perturbed protein homeostasis in the endoplasmic reticulum (ER) by inhibiting the expression of chaperone proteins and genes involved in ER-associated degradation. This led to the activation of the PERK-eIF2α pathway, which caused dysfunction of hepatic lipid metabolism. Induction of oxidative stress and activation of the Nrf2/Keap1 pathway were also involved in the PS NP-induced hepatic lipid accumulation. These findings highlight the potential adverse effects of environmental MPs/NPs on aquatic organisms, raising concerns about their ecotoxicity and food safety.

Diterpenoids and Their Glycosides from the Stems of Tinospora crispa with Beta-Cell Protective Activity.

Seven previously undescribed diterpenoids, tinocrisposides A-D (1-4) and borapetic acids A (5), B (6), and C (7), together with 16 known compounds, were isolated from the stem of Tinospora crispa (Menispermaceae). The structures of the new isolates were elucidated by spectroscopic and chemical methods. The ß-cell protective effect of the tested compounds was examined on insulin-secreting BRIN-BD11 cells under dexamethasone treatment. Diterpene glycosides 12, 14-16, and 18 presented a substantial protective effect on BRIN-BD11 cells treated with dexamethasone in a dose-dependent manner. Compounds 4 and 17 with two sugar moieties exhibited clear protective effects on ß-cells.

Simultaneous ground-state cooling of multiple degenerate mechanical modes through the cross-Kerr effect.

Simultaneous ground-state cooling of multiple degenerate mechanical modes is a difficult issue in optomechanical systems, owing to the existence of the dark mode effect. Here we propose a universal and scalable method to break the dark mode effect of two degenerate mechanical modes by introducing cross-Kerr (CK) nonlinearity. At most, four stable steady states can be achieved in our scheme in the presence of the CK effect, unlike the bistable behavior of the standard optomechanical system. Under a constant input laser power, the effective detuning and mechanical resonant frequency can be modulated by the CK nonlinearity, resulting in an optimal CK coupling strength for cooling. Similarly, there will be an optimal input laser power for cooling when the CK coupling strength stays fixed. Our scheme can be extended to break the dark mode effect of multiple degenerate mechanical modes by introducing more than one CK effect. To fulfill the requirement of the simultaneous ground-state cooling of N multiple degenerate mechanical modes, N - 1 CK effects with different strengths are needed. Our proposal provides new, to the best of our knowledge. insights into dark mode control and might pave the way to manipulating multiple quantum states in a macroscopic system.

Simultaneous Determination and Health Risk Assessment of Four High Detection Rate Pesticide Residues in Pu'er Tea from Yunnan, China.

Four pesticides with a high detection rate in Pu'er tea have been determined by a QuEChERS (quick, easy, cheap, effective, rugged, safe) method with multiwalled carbon nanotubes (MWCNTs), and combined ultrahigh-performance liquid chromatography-triple quadrupole linear ion trap-tandem mass spectrometry (UHPLC-QTRAP-MS/MS). MWCNs have been compared with other common purification materials, and found to be superior. The matrix effect was systematically studied, and the results show that the MWCNs can quickly and effectively reduce matrix interference values, which were in the range from -17.8 to 13.8. The coefficients (R2) were greater than 0.99, with the limit of quantification ranging from 0.1 to 0.5 µg/kg, and the recovery rate ranging from 74.8% to 105.0%, while the relative standard deviation (RSD) ranged from 3.9% to 6.6%. A total of 300 samples, taken from three areas in which Yunnan Pu'er tea was most commonly produced, tested for four pesticides. The results show that the detection rate of tolfenpyrad in Pu'er tea was 35.7%, which is higher than other pesticides, and the lowest was indoxacarb, with 5.2%. The residual concentrations of chlorpyrifos, triazophos, tolfenpyrad and indoxacarb ranged from 1.10 to 5.28, 0.014 to 0.103, 1.02 to 51.8, and 1.07 to 4.89 mg/kg, respectively. By comparing with China's pesticide residue limits in tea (GB 2763-2021), the over standard rates of chlorpyrifos, tolfenpyrad, and indoxacarb were 4.35%, 0.87% and 0%, respectively. The risk assessment result obtained with the hazard quotient (HQ) method shows that the HQ of the four pesticides was far less than one, indicating that the risk is considered acceptable for the four pesticides in Pu'er tea. The largest HQ was found for tolfenpyrad, 0.0135, and the smallest was found for indoxacarb, 0.000757, but more attention should be paid to tolfenpyrad in daily diets in the future, because its detection rate, and residual and residual median were all relatively high.

Demonstration of Yb3+-doped and Er3+/Yb3+-codoped on-chip microsphere lasers.

Rare-earth-doped on-chip microlasers are of great significance in both fundamental research and engineering. To the best of our knowledge, this is the first report of Yb3+-doped and Er3+/Yb3+-codoped on-chip microsphere lasers fabricated via sol-gel synthesis. Laser emissions were observed in a band around 1040 nm in both Yb3+-doped and Er3+/Yb3+-codoped resonators pumped at 980 nm and had measured ultralow thresholds of 5.2 µW and 0.6 µW, respectively. Both single-mode and multi-mode emissions were recorded around 1040 nm in these lasers. Single-mode and two-mode emissions were obtained at 1550 nm in the Er3+/Yb3+-codoped lasers when pumped at 980 nm and 1460 nm, respectively. Furthermore, quality factors induced by different loss mechanisms in the microsphere lasers are theoretically estimated. These resonators are expected to contribute to the high-density integration of on-chip silica-based microlasers.

Scalable higher-order exceptional surface with passive resonators.

The sensitivity of perturbation sensing can be effectively enhanced with higher-order exceptional points due to the nonlinear response to frequency splitting. However, experimental implementation is challenging since all the parameters need to be precisely prepared. The emergence of an exceptional surface (ES) improves the robustness of the system to the external environment, while maintaining the same sensitivity. Here, we propose, to our knowledge, the first scalable protocol for realizing a photonic high-order ES with passive resonators. By adding one or more additional passive resonators in the low-order ES photonic system, the three- or arbitrary N-order ES is constructed and proved to be easily realized in experiment. We show that the sensitivity is enhanced and the experimental demonstration is more resilient against fabrication errors. The additional phase-modulation effect is also investigated.

Image reconstruction with the chaotic fiber laser in scattering media.

The reconstruction of the size, position, optical properties, and structure of the object in scattering media was realized with a chaotic fiber laser. The light from the chaotic fiber laser was split into two parts. One part was used as the detection signal to detect the object, and the other was used as the reference signal; then, the two signals were cross correlated. The attenuation of light in scattering media was attributed to scattering and absorption. The theoretical model of the peak value of cross correlation of the chaotic signals as projection data were established by the attenuation law, and the filtered back-projection algorithms were used to realize the image reconstruction. The mean squared error, the normalized mean squared error, the peak signal-to-noise ratio, and the structural similarity index of the reconstructed image were analyzed. The results show that the high resolution of the reconstructed image benefits from the high signal-to-noise ratio with the chaotic fiber laser based on a delta-like cross-correlation function.

Manipulation of optomechanically induced transparency and absorption by indirectly coupling to an auxiliary cavity mode.

We theoretically study the optomechanically induced transparency (OMIT) and absorption (OMIA) phenomena in a single microcavity optomechanical system, assisted by an indirectly coupled auxiliary cavity mode. We show that the interference effect between the two optical modes plays an important role and can be used to control the multiple-pathway induced destructive or constructive interference effect. The three-pathway interference could induce an absorption dip within the transparent window in the red sideband driving regime, while we can switch back and forth between OMIT and OMIA with the four-pathway interference. The conversion between the transparency peak and absorption dip can be achieved by tuning the relative amplitude and phase of the multiple light paths interference. Our system proposes a new platform to realize multiple pathways induced transparency and absorption in a single microcavity and a feasible way for realizing all-optical information processing.

Continuous regional arterial infusion for the treatment of severe acute pancreatitis: a meta-analysis.

BACKGROUND: Continuous regional arterial infusion (CRAI) is a drug delivery system, which dramatically increases the drug concentration in the pancreas. Previous clinical and basic studies have demonstrated the possible therapeutic efficacy of CRAI for severe acute pancreatitis (SAP). This meta-analysis of all published randomized controlled trials (RCTs) was conducted to assess the efficacy and safety of CRAI for the treatment of SAP. DATA SOURCES: Up to August 10, 2014, RCTs comparing CRAI with intravenous infusion for SAP in PubMed, Embase, EBSCO, MEDLINE, Science Citation Index Expanded, Cochrane Library, China Academic Journals Full-Text Database, Chinese Biomedical Literature Database, and Chinese Scientific Journals Database were selected by two independent reviewers. The relative risk (RR) and their 95% confidence intervals (CI) for duration of elevated serum amylase and urine amylase, duration of abdominal pain, infection rate, incidence of complication, overall mortality, curative rate, hospital stay and details of subgroup analysis were extracted. Meta-analyses were made using the software Review Manager (RevMan version 5.10). RESULTS: Six RCTs with 390 patients meeting the inclusion criteria were included in the final analysis. Compared with intravenous infusion route, CRAI significantly shortened the duration of elevated urine amylase (MD=-2.40, 95% CI=-3.20, -1.60; P<0.00001) and the duration of abdominal pain (MD=-1.46, 95% CI=-1.94, -0.98; P<0.00001), decreased the incidence of complication (RR=0.35, 95% CI=0.15, 0.81; P=0.01) and overall mortality (RR=0.25, 95% CI=0.08, 0.78; P=0.02), shortened the duration of hospital stay (MD=-10.36, 95% CI=-17.05, -3.68; P=0.002), and increased the curative rate (RR=1.66, 95% CI=1.13, 2.46; P=0.01). No mortality and catheter-related infections due to CRAI administration was reported in these studies. Subgroup analysis showed that the combination of drug administration via CRAI did not significantly improve the outcomes. CONCLUSION: CRAI is effective for the treatment of SAP, and the combination of drug administration via CRAI did not have a significant effect on the improvement of the outcomes.

Threats of per- and poly-fluoroalkyl pollutants to susceptible populations.

Environmental exposure to per- and poly-fluoroalkyl substances (PFAS) has raised significant global health concerns due to potential hazards in healthy adults. However, the impact of PFAS on susceptible populations, including pregnant individuals, newborns, the older people, and those with underlying health conditions, has been overlooked. These susceptible groups often have physiological changes that make them less resilient to the same exposures. Consequently, there is an urgent need for a comprehensive understanding of the health risks posed by PFAS exposure to these populations. In this review, we delve into the potential health risks of PFAS exposure in these susceptible populations. Equally important, we also examine and discuss the molecular mechanisms that underlie this susceptibility. These mechanisms include the induction of oxidative stress, disruption of the immune system, impairment of cellular metabolism, and alterations in gut microbiota, all of which contribute to the enhanced toxicity of PFAS in susceptible populations. Finally, we address the primary research challenges and unresolved issues that require further investigation. This discussion aims to foster research for a better understanding of how PFAS affect susceptible populations and to pave the way for strategies to minimize their adverse effects.

Protective Effects of Pear Extract on Skin from In Vitro and In Vivo UVA-Induced Damage.

The ancient Chinese medical book "Compendium of Materia Medica" records that pears can relieve symptoms of respiratory-related diseases. Previous research has shown that pear Pyrus Pyrifolia (Burm.f.) Nakai has antioxidant and anti-inflammatory properties. However, the anti-inflammatory, antioxidant, and anti-photoaging protective effects of Pyrus pyrifolia (Burm.f.) Nakai seed components have not been studied. Ultraviolet light (UV) causes skin inflammation, damages the skin barrier, and is an important cause of skin photoaging. Therefore, UV light with a wavelength of 365 nm was used to irradiate HaCaT and mice. Western blot, real-time quantitative polymerase chain reaction, and fluorescence imaging system were used to explore its anti-UVA mechanism. Dialysis membrane and nuclear magnetic resonance were used for the chemical constituent analysis of pear seed water extract (PSWE). We found that PSWE can significantly reduce UVA-induced skin cell death and mitogen-activated protein kinase phosphorylation and can inhibit the mRNA expression of UVA-induced cytokines (including IL-1ß, IL-6, and TNF-α). In addition, PSWE can also reduce the generation of oxidative stress within skin cells. In vivo experimental studies found that PSWE pretreatment effectively reduced transepidermal water loss, inflammation, redness, and dryness in hairless mice. The molecular weight of the active part of pear water extract is approximately 384. Based on the above results, we first found that pear seeds can effectively inhibit oxidative stress and damage caused by UVA. It is a natural extract with antioxidant properties and anti-aging activity that protects skin cells and strengthens the skin barrier.

[Status of household disaster preparedness and affecting factors among the general public of four counties in Shaanxi].

OBJECTIVE: To investigate the status of household disaster preparedness in 4 counties of Shaanxi province and explore the affecting factors. METHODS: During the period from September to October in 2008, multi-stage sampling was used to select subjects from urban and rural residents in Xincheng district, Hantai district, Fuping county and Xunyang county of Shaanxi province. Questionnaire survey was conducted among 1945 subjects aged 18-88 years to investigate their experience and expectation of disaster events, preparedness knowledge, activities and emergency supplies. Logistic regression was used to analyze the factors influencing household disaster preparedness. RESULTS: The average age of the 1945 subjects was (43.55 ± 12.76) years old. A total of 7.12% (138/1939) of respondents never experienced disaster. Earthquake and fire (57.35% (1175/2049), 19.81% (406/2049), respectively) were rated as the two disasters most likely to occur. The awareness rate of knowledge about household disaster preparedness was 51.43% (989/1923), and 23.41% (454/1939) discussed how to prepare for disaster with their family, only 9.27% (179/1932) attended evacuation drill. The rates of preparing household emergency supplies were 23.64% (230/973), 30.56% (55/180), 31.19% (141/452) and 54.49% (97/178) for urban residents, subjects with junior college or above education, subjects having frequent family discussions of disaster preparedness and subjects participating in emergency rescue drills, respectively. For subjects with junior high school, senior high school and junior college or higher education, the likelihood of preparing household emergency supplies was 5.02 (95%CI: 1.12 - 22.42), 5.74 (95%CI: 1.27 - 26.04) and 6.84 (95%CI: 1.44 - 32.39) times as that of illiterate, respectively. Urban residents, subjects who often discussed disaster preparedness with their family, and who participated in emergency rescue drills were more likely to prepare emergency supplies than rural residents (OR = 4.38, 95%CI: 2.74 - 7.00), those who never discussed (OR = 4.99, 95%CI: 2.52 - 9.91), and who didn't participate (OR = 5.72, 95%CI: 3.84 - 8.51). CONCLUSION: The residents in 4 counties of Shaanxi lack comprehensive knowledge and appropriate activities of disaster preparedness, the rate of preparing household emergency supplies is low. Higher education, living in urban area, frequent family discussions of disaster preparedness and participating in emergency rescue drills are facilitating factors of preparing household emergency supplies.

Enhanced Sensing Mechanism Based on Shifting an Exceptional Point.

Non-Hermitian systems associated with exceptional points (EPs) are expected to demonstrate a giant response enhancement for various sensors. The widely investigated enhancement mechanism based on diverging from an EP should destroy the EP and further limits its applications for multiple sensing scenarios in a time sequence. To break the above limit, here, we proposed a new enhanced sensing mechanism based on shifting an EP. Different from the mechanism of diverging from an EP, our scheme is an EP nondemolition and the giant enhancement of response is acquired by a slight shift of the EP along the parameter axis induced by perturbation. The new sensing mechanism can promise the most effective response enhancement for all sensors in the case of multiple sensing in a time sequence. To verify our sensing mechanism, we construct a mass sensor and a gyroscope with concrete physical implementations. Our work will deepen the understanding of EP-based sensing and inspire designing various high-sensitivity sensors in different physical systems.

[Status quo of lifestyle among women of five occupations in six provinces of China].

OBJECTIVE: To learn the status quo of lifestyle among women of five occupations in six provinces of China. METHODS: A questionnaire was administered among 7416 women from five occupations (civil servants, teachers of elementary and high schools, technical staff, enterprise managers and physical laborers) in Beijing, Hebei, Jilin, Hubei, Ningxia and Gansu of China. The sample was selected by multi-stage stratified cluster random sampling method from December 2009 to June 2010. The questionnaire information included demographic characteristics, diet, sleep habit, smoking, physical exercise. The χ(2) test was used to analyze the different in life style of different occupations. RESULTS: There were 7416 valid questionnaires received, and the valid rate of the questionnaires was 97.58% (7416/7682). About 38.00% (2818/7416) respondents preferred to bland diet and 28.44% (2109/7416) preferred to salty and oily food and 33.56% (2489/7416) had no preference. The proportion of sleep time between seven and eight hours per day was highest (accounting for 56.23%, 4154/7416), 25.27% (1867/7416) with sleep time less than seven hours. Among the population who had the sleep time less seven hours, teacher that had the highest rate accounted for 33.19% (531/1607) and technical staff had the lowest rate accounted for 21.05% (301/1401) (P < 0.01). Most of respondents were non-smokers, accounting for 93.10% (6869/7416). 22.73% (1671/7416) respondents passively smoked. The proportion of always passive smoking was highest among civil servants and lowest among teachers, accounting for 26.60% (404/1531) and 18.71% (298/1607), respectively. The proportion of having no physical exercises was highest, accounting for 62.87% (4637/7416). The proportion of having three times physical exercises per week was 12.68% (935/7416). The proportion of having no physical exercises among physical laborers (66.42%, 912/1386), enterprise managers (66.64%, 987/1491) and teachers (62.40%, 999/1607) were higher than others and the proportion of having physical exercises per week among technical staff was 40.83% (569/1401), higher than others (P < 0.01). The proportion of person who worked in sitting quietly beyond six hours per day was 42.62% (3146/7416). The technical staff had the higher rate than other occupational populations (P < 0.01), accounting for 57.83% (809/1401). CONCLUSION: The female occupational population had some unhealthy lifestyles, such as taking in high salt food, lacking of sleep, smoking and passive smoking, lacking of physical exercises and working in sitting quietly. Different occupational populations had different unhealthy lifestyles.

[Study on lifestyle and self-rated health among 5 kinds of occupational populations in 6 provinces in China].

OBJECTIVE: To know about the status of self-rated health and life style among 5 kinds of occupational populations in 6 provinces in China and to explore the influencing factors related with health of the occupational population. METHODS: From May to August 2009, a total of 13 492 persons aged 18 - 60 years including civil servants, scientific and technical personnel, administrative staff, teachers and physical workers were selected by multi-stage stratified sampling from Beijing city, Ningxia Hui autonomous region, Liaoning, Zhejiang, Hubei and Qinghai provinces to undergo surveys on the Lifestyle of Occupational Population in Urban in China and Self-rated Health Measurement Scale Version 1.0 (SRHMS V1.0). The effects of lifestyles on health scores were analyzed by logistic linear regression. RESULTS: Overall, 13 073 valid questionnaires of the Lifestyle of Occupational Population in Urban in China and 13 177 valid questionnaires of SRHMS V1.0 were collected. The valid rate was 96.9% and 97.7% respectively. Among the respondents, 46.9% (6136/13073) ate timely in a day, 50.9% (6658/13 073) ate breakfast every day, 27.8% (3635/13 073) worked over 8 hours per day, 31.0% (4057/13 073) didn't do any exercises, 14.6% (1906/13073) sat for over 4 hours in spare time, 39.3% (5137/13 073) were drinking and 24.8% (3230/13 073) were current smokers. The average score of SRHMS of all respondents was 73.34 +/- 11.86, of which the civil servant had the highest score (74.83 +/- 11.89) while the teacher had the lowest score (71.65 +/- 11.44, P < 0.05). The results of multiple linear regression showed that females (b = -0.945, b' = -0.041), the elderly (b = -0.098, b' = -0.087), teachers (b = - 2.151, b' = -0.074), the divorced (b = -1.607, b' = -0.021), the widowed (b = -2.926, b' = -0.019), and smokers (b = -1.198, b' = -0.045) were with worse condition. Respondents with higher education (b = 0.588, b' = 0.037), eating timely (b = 2.301, b' = 0.141), eating breakfast every day (b = 1.503, b' = 0.096), paying more attention on diet (b = 0.499, b' = 0.021) and doing more exercises (b = 1.820, b' = 0.058) had better condition. CONCLUSION: Eating irregularly, working long hours, lack of exercise, sitting for long hours, smoking and drinking were common among occupational population. The self-rated physical health status was associated with gender, age, education level, occupation, diet and exercise.

iCEMIGE: Integration of CEll-morphometrics, MIcrobiome, and GEne biomarker signatures for risk stratification in breast cancers.

BACKGROUND: The development of precision medicine is essential for personalized treatment and improved clinical outcome, whereas biomarkers are critical for the success of precision therapies. AIM: To investigate whether iCEMIGE (integration of CEll-morphometrics, MIcro biome, and GEne biomarker signatures) improves risk stratification of breast cancer (BC) patients. METHODS: We used our recently developed machine learning technique to identify cellular morphometric biomarkers (CMBs) from the whole histological slide images in The Cancer Genome Atlas (TCGA) breast cancer (TCGA-BRCA) cohort. Multivariate Cox regression was used to assess whether cell-morphometrics prognosis score (CMPS) and our previously reported 12-gene expression prognosis score (GEPS) and 15-microbe abundance prognosis score (MAPS) were independent prognostic factors. iCEMIGE was built upon the sparse representation learning technique. The iCEMIGE scoring model performance was measured by the area under the receiver operating characteristic curve compared to CMPS, GEPS, or MAPS alone. Nomogram models were created to predict overall survival (OS) and progress-free survival (PFS) rates at 5- and 10-year in the TCGA-BRCA cohort. RESULTS: We identified 39 CMBs that were used to create a CMPS system in BCs. CMPS, GEPS, and MAPS were found to be significantly independently associated with OS. We then established an iCEMIGE scoring system for risk stratification of BC patients. The iGEMIGE score has a significant prognostic value for OS and PFS independent of clinical factors (age, stage, and estrogen and progesterone receptor status) and PAM50-based molecular subtype. Importantly, the iCEMIGE score significantly increased the power to predict OS and PFS compared to CMPS, GEPS, or MAPS alone. CONCLUSION: Our study demonstrates a novel and generic artificial intelligence framework for multimodal data integration toward improving prognosis risk stratification of BC patients, which can be extended to other types of cancer.

Application of antibody-conjugated small intestine submucosa to capture urine-derived stem cells for bladder repair in a rabbit model.

The need for bladder reconstruction and side effects of cystoplasty have spawned the demand for the development of alternative material substitutes. Biomaterials such as submucosa of small intestine (SIS) have been widely used as patches for bladder repair, but the outcomes are not fully satisfactory. To capture stem cells in situ has been considered as a promising strategy to speed up the process of re-cellularization and functionalization. In this study, we have developed an anti-CD29 antibody-conjugated SIS scaffold (AC-SIS) which is capable of specifically capturing urine-derived stem cells (USCs) in situ for tissue repair and regeneration. The scaffold has exhibited effective capture capacity and sound biocompatibility. In vivo experiment proved that the AC-SIS scaffold could promote rapid endothelium healing and smooth muscle regeneration. The endogenous stem cell capturing scaffolds has thereby provided a new revenue for developing effective and safer bladder patches.

Structural insights into the substrate selectivity of α-oxoamine synthases from marine Vibrio sp. QWI-06.

Pyridoxal phosphate (PLP)-dependent α-oxoamine synthases are generally believed to be responsible for offloading and elongating polyketides or catalyzing the condensation of amino acids and acyl-CoA thioester substrates, such as serine into sphingolipids and cysteate into sulfonolipids. Previously, we discovered vitroprocines, which are tyrosine- and phenylalanine-polyketide derivatives, as potential new antibiotics from the genus Vibrio. Using bioinformatics analysis, we identified putative genes of PLP-dependent enzyme from marine Vibrio sp. QWI-06, implying a capability to produce amino-polyketide derivatives. One of these genes was cloned, and the recombinant protein, termed Vibrio sp. QWI-06 α-oxoamine synthases-1 (VsAOS1), was overexpressed for structural and biochemical characterization. The crystal structure of the dimeric VsAOS1 was determined at 1.8-Å resolution in the presence of L-glycine. The electron density map indicated a glycine molecule occupying the pyridoxal binding site in one monomer, suggesting a snapshot of the initiation process upon the loading of amino acid substrate. In mass spectrometry analysis, VsAOS1 strictly acted to condense L-glycine with C12 or C16 acyl-CoA, including unsaturated acyl analog. Furthermore, a single residue replacement of VsAOS1 (G243S) allowed the enzyme to generate sphingoid derivative when L-serine and lauroyl-CoA were used as substrates. Our data elucidate the mechanism of substrate binding and selectivity by the VsAOS1 and provide a thorough understanding of the molecular basis for the amino acid preference of AOS members.

Proteomics analysis reveals diabetic kidney as a ketogenic organ in type 2 diabetes.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. To date, the molecular mechanisms of DN remain largely unclear. The present study aimed to identify and characterize novel proteins involved in the development of DN by a proteomic approach. Proteomic analysis revealed that 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase 2 (HMGCS2), the key enzyme in ketogenesis, was increased fourfold in the kidneys of type 2 diabetic db/db mice. Consistently, the activity of HMGCS2 in kidneys and 24-h urinary excretion of the ketone body ß-hydroxybutyrate (ß-HB) were significantly increased in db/db mice. Immunohistochemistry, immunofluorescence, and real-time PCR studies further demonstrated that HMGCS2 was highly expressed in renal glomeruli of db/db mice, with weak expression in the kidneys of control mice. Because filtered ketone bodies are mainly reabsorbed in the proximal tubules, we used RPTC cells, a rat proximal tubule cell line, to examine the effect of the increased level of ketone bodies. Treating cultured RPTC cells with 1 mM ß-HB significantly induced transforming growth factor-ß1 expression, with a marked increase in collagen I expression. ß-HB treatment also resulted in a marked increase in vimentin protein expression and a significant reduction in E-cadherin protein levels, suggesting an enhanced epithelial-to-mesenchymal transition in RPTCs. Collectively, these findings demonstrate that diabetic kidneys exhibit excess ketogenic activity resulting from increased HMGCS2 expression. Enhanced ketone body production in the diabetic kidney may represent a novel mechanism involved in the pathogenesis of DN.