The effects of standardized intravenous treprostinil in pulmonary arterial hypertension patients after total cavo-pulmonary connection procedure.

OBJECTIVE: Total cavo-pulmonary connection (TCPC) is a palliative treatment for single ventricular malformations. For high-risk patients (preoperative mean pulmonary arterial pressure, mPAP > 15 mmHg), between the inhaled and oral targeted medications, the application of intravenous treprostinil as a bridge therapy to achieve "seamless" management is core postoperative treatment. This study intends to explore the effect of different administration regimens on early postoperative recovery. METHODS: This was a retrospective cohort study. High-risk pediatric patients (age ≤ 14 years) who underwent TCPC procedure in Fu Wai Hospital from 2015 to 2022 were included. Since the regimen of treprostinil was standardized in our center in 2021, the patients in 2020 and before were included in group 1, patients in 2021 and 2022 were included in group 2. The hemodynamic parameters were compared before and after the maintenance dose of treprostinil. The differences of demographic characteristics, surgical data and postoperative recovery were compared between the two groups. RESULTS: A total of 51 pediatric patients were included. Group 1 included 35 patients who received treprostinil at 1-3 postoperative days and an average dose of 12 ± 4 ng/(kg·min). Group 2 included 16 patients who received treprostinil within postoperative 1 day and an average dose of 22 ± 7 ng/(kg·min). There were no significant differences between the two groups in terms of age, weight, preoperative percutaneous oxygen saturation and mPAP,  heterotaxy syndrome, TCPC procedure type, other concurrent procedure, cardiopulmonary bypass time and aortic cross-clamp proportion (p > 0.05). After 24 h of treprostinil treatment, the mPAP in group 1 reduced from 17 ± 3 mmHg to 15 ± 2 mmHg (p < 0.001), and in group 2 from 17 ± 2 mmHg to 14 ± 2 mmHg (p < 0.001), with no difference between groups. In the postoperative recovery, patients in Group 2 exhibited a reduced duration of mechanical ventilation, 19 (11, 25) hours vs 69 (23, 189) hours, p = 0.001; a shorter stay in the ICU, 8 (6, 12) days vs 16 (9,26) days, p = 0.006; and a shorter postoperative length of stay, 27 (17,55) days vs 39 (29,58) days, p = 0.032. Patients in Group 2 also exhibited a lower incidence of thromboembolic events, 0 (0/26) vs 26% (9/35), p = 0.043; and the need for renal replacement therapy, 0 (0/26) vs 31% (11/35), p = 0.011. CONCLUSION: Treprostinil reduces pulmonary artery pressure after TCPC procedure. The standardized application of treprostinil may improve the postoperative recovery which should be proven by randomized controlled trials or matched cohort studies in the future.

Deciphering the Underlying Mechanism of the Fourth Entity in Medium-Entropy NiCoFeMP toward Boosting Oxygen Evolution Electrocatalysis.

High-/medium-entropy materials have been explored as promising electrocatalysts for water splitting due to their unique physical and chemical properties. Unfortunately, state-of-the-art materials face the dilemma of explaining the enhancement mechanism, which is now limited to theoretical models or an unclear cocktail effect. Herein, a medium-entropy NiCoFeMnP with an advanced hierarchical particle-nanosheet-tumbleweed nanostructure has been synthesized via simple precursor preparation and subsequent phosphorization. Evaluated as the electrocatalyst for oxygen evolution reaction (OER), the medium-entropy NiCoFeMnP displays a lower overpotential of 272 mV at a current density of 10 mA cm-2, and more favorable kinetics than the binary NiFeP, ternary NiCoFeP, quaternary NiCoFeCuP and NiCoFeCrP counterparts, and other reported high-/medium-entropy electrocatalysts. Careful experimental analyses reveal that the incorporation of Mn can significantly regulate the electronic structure of Ni, Co, and Fe sites. More importantly, the Mn introduction and entropy stabilization effect in the reconstructed metal (oxy)hydroxide simultaneously promote the lattice oxygen mechanism, improving the activity. This work sheds new light on the design of high-/medium-entropy materials from an in-depth understanding of the underlying mechanism for improving energy conversion efficiency.

Clinical value of transperineal ultrasound in evaluating the diagnostic grade of rectocele in Chinese women with obstructed defecation syndrome: An observational study.

We aimed to evaluate the effectiveness of transperineal ultrasound (TPUS) in diagnosing rectocele, rectal intussusception (RI), enterocele, perineal descent (PD), and cystocele in Chinese women with obstructed defecation syndrome (ODS), and to determine the grading of rectocele via TPUS. Between January 2019 and December 2021, 107 obstructed defecation syndrome patients, with a mean age of 49.76 years, received TPUS and defecation proctography (DEP). Both methods were used to diagnose anorectal angle, rectocele, RI, enterocele, and PD, while cystocele and uterine prolapse were diagnosed only through TPUS. Agreement between DEP and TPUS diagnostic results was compared using Cohen kappa statistics. Seventy-six rectoceles were reported following DEP and 72 after TPUS. DEP detected 7 enteroceles, 6 of which were diagnosed simultaneously by TPUS. 43 patients presented dyssynergic defecation (DD) upon DEP, while 51 upon TPUS. DEP and TPUS detected PD in 13 and 11 patients respectively, and RI in 82 and 73, respectively. Rectocele (kappa = 0.738), RI (kappa = 0.711), DD (kappa = 0.774), enterocele (kappa = 0.847), and PD (kappa = 0.625) were obtained by Cohen kappa statistics, which indicated a good agreement between DEP and TPUS. The cutoff values for the diagnosis of moderate and severe rectocele with TPUS were 12.05 mm (AUC: 0.941) and 18.50 mm (AUC: 0.977), respectively. The DEP-determined and TPUS-determined anorectal angles were significantly correlated in the resting and Valsalva states (P < .01). Compared with DEP, while maintaining good agreement in detecting rectocele, RI, DD, enterocele, and PD, TPUS is a repeatable and noninvasive alternative. Threshold values of 12.05 mm and 18.50 mm on TPUS may diagnose moderate and severe rectocele, respectively.

Vulnerability extraction and prediction method based on improved information gain algorithm.

More and more attention has been paid to computer security, and its vulnerabilities urgently need more sensitive solutions. Due to the incomplete data of most vulnerability libraries, it is difficult to obtain pre-permission and post-permission of vulnerabilities, and construct vulnerability exploitation chains, so it cannot to respond to vulnerabilities in time. Therefore, a vulnerability extraction and prediction method based on improved information gain algorithm is proposed. Considering the accuracy and response speed of deep neural network, deep neural network is adopted as the basic framework. The Dropout method effectively reduces overfitting in the case of incomplete data, thus improving the ability to extract and predict vulnerabilities. These experiments confirmed that the excellent F1 and Recall of the improved method reached 0.972 and 0.968, respectively. Compared to the function fingerprints vulnerability detection method and K-nearest neighbor algorithm, the convergence is better. Its response time is 0.12 seconds, which is excellent. To ensure the reliability and validity of the proposed method in the face of missing data, the reliability and validity of Mask test are verified. The false negative rate was 0.3% and the false positive rate was 0.6%. The prediction accuracy of this method for existing permissions reached 97.9%, and it can adapt to the development of permissions more actively, so as to deal with practical challenges. In this way, companies can detect and discover vulnerabilities earlier. In security repair, this method can effectively improve the repair speed and reduce the response time. The prediction accuracy of post-existence permission reaches 96.8%, indicating that this method can significantly improve the speed and efficiency of vulnerability response, and strengthen the understanding and construction of vulnerability exploitation chain. The prediction of the posterior permission can reduce the attack surface of the vulnerability, thus reducing the risk of breach, speeding up the detection of the vulnerability, and ensuring the timely implementation of security measures. This model can be applied to public network security and application security scenarios in the field of computer security, as well as personal computer security and enterprise cloud server security. In addition, the model can also be used to analyze attack paths and security gaps after security accidents. However, the prediction of post-permissions is susceptible to dynamic environments and relies heavily on the updated guidance of security policy rules. This method can improve the accuracy of vulnerability extraction and prediction, quickly identify and respond to security vulnerabilities, shorten the window period of vulnerability exploitation, effectively reduce security risks, and improve the overall network security defense capability. Through the application of this model, the occurrence frequency of security vulnerability time is reduced effectively, and the repair time of vulnerability is shortened.

GATDE: A graph attention network with diffusion-enhanced protein-protein interaction for cancer classification.

Cancer classification is crucial for effective patient treatment, and recent years have seen various methods emerge based on protein expression levels. However, existing methods oversimplify by assuming uniform interaction strengths and neglecting intermediate influences among proteins. Addressing these limitations, GATDE employs a graph attention network enhanced with diffusion on protein-protein interactions. By constructing a weighted protein-protein interaction network, GATDE captures the diversity of these interactions and uses a diffusion process to assess multi-hop influences between proteins. This information is subsequently incorporated into the graph attention network, resulting in precise cancer classification. Experimental results on breast cancer and pan-cancer datasets demonstrate that GATDE surpasses current leading methods. Additionally, in-depth case studies further validate the effectiveness of the diffusion process and the attention mechanism, highlighting GATDE's robustness and potential for real-world applications.

Coronary thrombosis and myocardial ischemia in Kawasaki disease: a case report.

BACKGROUND: Coronary artery thrombosis and myocardial ischemia caused by giant coronary aneurysms are the main causes of death in children with Kawasaki disease. The use of thrombolytic therapy in children with Kawasaki disease who have coronary thrombosis is a controversial topic, especially with respect to the timing of treatment. CASE PRESENTATION: In this article, we report a case of a child aged two years and nine months with Kawasaki disease whose coronary arteries had no involvement in the acute phase. However, by only one week after discharge, the patient returned because we found giant coronary aneurysms complicated by thrombosis via echocardiography. Despite aggressive thrombolytic therapy, the child developed myocardial ischemia during thrombolytic therapy. Fortunately, because of timely treatment, the child's thrombus has dissolved, and the myocardial ischemia has resolved. CONCLUSIONS: This case suggests that for patients at high risk of coronary artery aneurysms, echocardiography may need to be reviewed earlier. Low-molecular-weight heparin should be added to antagonize the early procoagulant effects of warfarin when warfarin therapy is initiated. In the case of first-detected coronary thrombosis, aggressive thrombolytic therapy may be justified, particularly during the acute and subacute phases of the disease course.

Role of Iodine Status and Lifestyle Behaviors on Goiter among Children and Adolescents: A Cross-Sectional Study in Zhejiang Province, China.

BACKGROUND: Iodine deficiency is a well-established cause of goiter, while the impact of lifestyle factors on goiter development remains underexplored. The study aims to explore the associations between iodine status, lifestyle factors, and the prevalence of goiter among children and adolescents in Zhejiang Province, China. METHODS: A cross-sectional survey was conducted in 2022 using a stratified multistage sampling, involving 2261 children aged 6-17. Among these 1562 participants underwent both urinalysis and thyroid ultrasound. Lifestyle factors were assessed through self-reported questionnaires. RESULTS: The prevalence of goiter in the study population was 10.8%. A high urinary iodine concentration (UIC) (>300 µg/L) was significantly associated with a decreased risk of goiter (OR = 0.49, 95%CI: 0.27-0.88). Excessive recreational screen time and a high frequency of dining out were associated with an increased Tvol, while adequate physical activity and sleep were inversely associated with goiter risk, while the combined effect of high UIC and healthy lifestyle showed a protective effect against goiter. CONCLUSION: Ensuring adequate iodine status and promoting healthy lifestyles are crucial for preventing goiter and enhancing thyroid health in children and adolescents, suggesting that public health strategies should integrate nutritional and lifestyle interventions.

Coherent Charge Transfer Reveals a Different Theoretical Limit of Power Conversion Efficiency in Organic Solar Cells.

The hopping charge transfer (CT) theory is used to explain the dynamics of traditional donor-acceptor (D-A) devices in organic solar cells (OSCs). But it is not applicable to the unconventional OSCs inspired by photosynthesis, referred to as Z-devices. In this study, we establish a universal heterojunction CT model in OSCs, based on the reported coherent CT in photosynthesis. Compared to the trade-off between energy loss and charge generation efficiency in the D-A device, we analyze its change in the Z-device. We introduce the "avalanche-like" CT of the Z-device induced by many-body Coulomb interaction and relevant experimental support. Combining with the Shockley-Queisser theory, we evaluate the theory limit power conversion efficiency of a D-A device and a Z-device. The Z-device has the potential to surpass the Shockley-Queisser limit of 33%.

An integrated textile of electrical signal sensing with visual indicators and energy supply for perspiration management.

Recent advances in wearable electronics have enabled the development of sweat sensors providing valuable information for healthcare monitoring. However, the limitations of sweat sensors are excessive dependence on external detection systems, the impossible to real-time visual signal transmission, and inadequate perspiration management. Herein, a single- and double-layer interwoven fabric (SDIF) is designed to achieve indicators of color visualization with an output of electrical signal and energy supply. After absorption of electrolyte, the SDIF can be rapidly activated, connected with the concentration, infiltrated volume, and environmental parameters, and the variational color of SDIF can provide visual indicators. The one tissue cycle of SDIF with three-weft intervals maintains a stable output voltage of ≈1.0 V, conducted by twisting, folding, dynamic bending, and reusing. Moreover, serial tissue cycles can be woven into large fabrics by connecting in series and parallel configurations for energy supply. The developed SDIF with an interweaving structural design using industrial-producible weaving technology provides the functionality of sweat adsorption and transportation, monitoring by recognition of color, and electrical signals to improve perspiration management.

Transplantation of chemically induced pluripotent stem-cell-derived islets under abdominal anterior rectus sheath in a type 1 diabetes patient.

We report the 1-year results from one patient as the preliminary analysis of a first-in-human phase I clinical trial (ChiCTR2300072200) assessing the feasibility of autologous transplantation of chemically induced pluripotent stem-cell-derived islets (CiPSC islets) beneath the abdominal anterior rectus sheath for type 1 diabetes treatment. The patient achieved sustained insulin independence starting 75 days post-transplantation. The patient's time-in-target glycemic range increased from a baseline value of 43.18% to 96.21% by month 4 post-transplantation, accompanied by a decrease in glycated hemoglobin, an indicator of long-term systemic glucose levels at a non-diabetic level. Thereafter, the patient presented a state of stable glycemic control, with time-in-target glycemic range at >98% and glycated hemoglobin at around 5%. At 1 year, the clinical data met all study endpoints with no indication of transplant-related abnormalities. Promising results from this patient suggest that further clinical studies assessing CiPSC-islet transplantation in type 1 diabetes are warranted.

A Comparative Study on the Dietary Iodine Intake and the Contribution Rates of Various Foods to the Dietary Iodine Intake among Residents in Zhejiang in 2010 and 2022.

We aim to analyze the changes in dietary iodine intake and the contribution rates of various foods to it after the reduction in salt iodine concentration in Zhejiang. We used data from two cross-sectional nutrition surveillance surveys conducted by the Zhejiang Provincial Center for Disease Control and Prevention in 2010 (9798 residents) and 2022 (5980 residents). In both surveys, multi-stage stratified and systematic sampling were adopted, and uniformly trained investigators conducted the dietary surveys using a 24 h dietary review and weighing record methods for 3 consecutive days. From 2010 to 2022, the median salt iodine concentration and the consumption rate of qualified iodized salt in Zhejiang households dropped from 28.80 to 22.08 mg/kg and from 76.65% to 64.20%, respectively. Moreover, the residents' median dietary iodine intake decreased from 277.48 to 142.05 µg/d. Significant interregional differences in dietary iodine intake were found in 2010 and 2022 (H = 639.175, p < 0.001; H = 588.592, p < 0.001, respectively); however, no significant differences existed between urban and rural areas (p > 0.05). From 2010 to 2022, the proportion of residents with dietary iodine intake below the estimated average requirement increased from 15.10% to 34.80%, while that of residents with intake above the tolerable upper limit decreased from 15.00% to 2.90%. The contribution rate of salt to dietary iodine intake among residents in Zhejiang decreased from 74.92% to 48.54%, showing an apparent overall downward trend despite the dietary intake being generally adequate (markedly inadequate in coastal regions). The salt iodine concentration and the consumption rate of qualified iodized salt in households in Zhejiang showed downward trends. Salt remained the main source of dietary iodine; however, its contribution decreased significantly. Zhejiang may need to reverse the trend of the continuous decline in the consumption rate of qualified iodized salt to protect the health of its residents.

Brachial plexopathy following stereotactic body radiation therapy in apical lung malignancies: A dosimetric pooled analysis of individual patient data.

BACKGROUND AND OBJECTIVES: The aim of this study is to establish dosimetric constraints for the brachial plexus at risk of developing grade ≥ 2 brachial plexopathy in the context of stereotactic body radiation therapy (SBRT). PATIENTS AND METHODS: Individual patient data from 349 patients with 356 apical lung malignancies who underwent SBRT were extracted from 5 articles. The anatomical brachial plexus was delineated following the guidelines provided in the atlases developed by Hall, et al. and Kong, et al.. Patient characteristics, pertinent SBRT dosimetric parameters, and brachial plexopathy grades (according to CTCAE 4.0 or 5.0) were obtained. Normal tissue complication probability (NTCP) models were used to estimate the risk of developing grade ≥ 2 brachial plexopathy through maximum likelihood parameter fitting. RESULTS: The prescription dose/fractionation schedules for SBRT ranged from 27 to 60 Gy in 1 to 8 fractions. During a follow-up period spanning from 6 to 113 months, 22 patients (6.3 %) developed grade ≥2 brachial plexopathy (4.3 % grade 2, 2.0 % grade 3); the median time to symptoms onset after SBRT was 8 months (ranged, 3-54 months). NTCP models estimated a 10 % risk of grade ≥2 brachial plexopathy with an anatomic brachial plexus maximum dose (Dmax) of 20.7 Gy, 34.2 Gy, and 42.7 Gy in one, three, and five fractions, respectively. Similarly, the NTCP model estimates the risks of grade ≥2 brachial plexopathy as 10 % for BED Dmax at 192.3 Gy and EQD2 Dmax at 115.4 Gy with an α/ß ratio of 3, respectively. Symptom persisted after treatment in nearly half of patients diagnosed with grade ≥2 brachial plexopathy (11/22, 50 %). CONCLUSIONS: This study establishes dosimetric constraints ranging from 20.7 to 42.7 Gy across 1-5 fractions, aimed at mitigating the risk of developing grade ≥2 brachial plexopathy following SBRT. These findings provide valuable guidance for future ablative SBRT in apical lung malignancies.

Immunometabolic Chaos in Septic Shock.

Septic shock is associated with over 40% mortality. The immune response in septic shock is tightly regulated by cellular metabolism and transitions from early hyper-inflammation to later hypo-inflammation. Patients are susceptible to secondary infections during hypo-inflammation. The magnitude of the metabolic dysregulation and the effect of plasma metabolites on the circulating immune cells in septic shock are not reported. We hypothesized that the accumulated plasma metabolites affect the immune response in septic shock during hypo-inflammation. Our study took a unique approach. Using peripheral blood from adult septic shock patients and healthy controls, we studied: 1. Whole blood stimulation ± E. Coli lipopolysaccharide (LPS: endotoxin) to analyze plasma TNF protein, and 2. Plasma metabolomic profile by Metabolon. Inc. 3. We exposed peripheral blood mononuclear cells (PBMCs) from healthy controls to commercially available carbohydrate, amino acid, and fatty acid metabolites and studied the response to LPS. We report that: 1. The whole blood stimulation of the healthy control group showed a significantly upregulated TNF protein, while the septic shock group remained endotoxin tolerant, a biomarker for hypo-inflammation. 2. A significant accumulation of carbohydrate, amino acid, fatty acid, ceramide, sphingomyelin, and TCA cycle pathway metabolites in septic shock plasma. 3. In vitro exposure to five metabolites repressed while two metabolites upregulated the inflammatory response of PBMCs to LPS. We conclude that the endotoxin-tolerant phenotype of septic shock is associated with a simultaneous accumulation of plasma metabolites from multiple metabolic pathways, and these metabolites fundamentally influence the immune response profile of circulating cells.

CD24-Targeted NIR-II Fluorescence Imaging Enables Early Detection of Colorectal Neoplasia.

Colorectal cancer (CRC) continues to be a major health issue even though screening methods have facilitated early detection. Despite the high sensitivity of white-light colonoscopy, it frequently overlooks invasive flat or depressed lesions, which can lead to the development of larger, advanced tumors. Fluorescence molecular imaging (FMI) offers a promising approach for early tumor detection by targeting specific molecular characteristics of lesions. CD24 is upregulated during the adenoma-to-CRC transition, providing a potential target for FMI. Here, we developed a second near-infrared window (NIR-II) fluorescent probe with a high affinity for CD24 and evaluated its efficacy and targeting ability in cellular models, murine models, and clinical samples of CRC. CD24 expression was elevated in 76% of adenomas and 80% of CRCs. In a colitis-associated cancer mouse model, NIR-II imaging with the CD24-targeted probe achieved a significantly higher tumor-to-background ratio compared to conventional NIR-I imaging. The probe demonstrated exceptional sensitivity (92%) and specificity (92%) for detecting CRC, including small lesions less than 1 mm in size. This led to the identification of precancerous lesions missed by white-light detection and lesions missed by NIR-I imaging. Moreover, ex vivo human tissue incubation with the probe supported the potential for intraprocedural lesion identification via topical probe application during colonoscopy. In conclusion, this study successfully demonstrates the potential of CD24-targeted NIR-II imaging for identifying colorectal neoplasia, highlighting its significance for early CRC detection in the gastrointestinal tract.

Phosphorylation of the transcription factor SlBIML1 by SlBIN2 kinases delays flowering in tomato.

Brassinosteroids (BRs) are well known for their important role in the regulation of plant growth and development. Plants with deficiency in BR signaling show delayed plant development and exhibit late flowering phenotypes. However, the precise mechanisms involved in this process require investigation. In this study, we cloned homologs of BRASSINOSTEROID INSENSITIVE 2 (SlBIN2), the GSK3-like protein kinase in tomato (Solanum lycopersicum). We characterized growth-related processes and phenotypic changes in the transgenic lines and found that SlBIN2s transgenic lines have delayed development and slow growing phenotypes. SlBIN2s work redundantly to negatively regulate BR signaling in tomato. Furthermore, the transcription factor SlBIN2.1-INTERACTING MYB-LIKE 1 (SlBIML1) was identified as a downstream substrate of SlBIN2s that SlBIN2s interact with and phosphorylate to synergistically regulate tomato developmental processes. Specifically, SlBIN2s modulated protein stability of SlBIML1 by phosphorylating multiple amino acid residues, including the sites Thr266 and Thr280. This study reveals a branch of the BR signaling pathway that regulates the vegetative growth phase and delays floral transition in tomato without the feedback affecting BR signaling. This information enriches our understanding of the downstream transduction pathway of BR signaling and provides potential targets for adjusting tomato flowering time.

Evaluation of ecosystem quality and stability based on key indicators and ideal reference frame: A case study of the Qinghai-Tibet Plateau.

China has explicitly prioritized the enhancement of ecosystem quality and stability(EQS) as a governmental objective. However, our understanding of systematic and comprehensive assessment methods for EQS remains limited. The development and investigation of corresponding evaluation frameworks and their underlying mechanisms remain insufficiently explored. This study employs the concept of an "ideal reference system and key indicators," integrating diverse ecosystem and human activity characteristics from perspectives such as ecosystem structure, function, and landscape vulnerability, to determine indicator weights using the Analytic Hierarchy Process(AHP) and entropy weight method, thereby constructing an evaluation framework for assessing the quality and stability of the Qinghai-Tibet Plateau(QTP) ecosystem. The spatiotemporal variations in EQS from 2000 to 2018 were examined, and the key driving factors were identified using the optimal parameter-based geographical detector (OPGD). The results indicate that the EQS of the QTP exhibit a spatial distribution pattern characterized by higher values in the southeast and lower values in the northwest. From 2000 to 2018, there has been a consistent improvement in the overall ecosystem quality and stability across the QTP. The EQS exhibit a significant synergistic effect, with high-high(26.59 ± 1.26%) and low-low(32.61 ± 1.45%) matching combinations becoming the predominant regional patterns. However, in climatic transition zones and glacial areas, the relationship between these factors is particularly distinctive, indicating ecosystem response mechanisms specific to certain natural environmental conditions. Vegetation cover(>0.697), evapotranspiration(>0.620), and precipitation(>0.688) are the primary natural factors influencing EQS, while the impact of human activities has become increasingly significant. Furthermore, the research findings underscore the positive effects of the variable climatic conditions of the QTP on ecosystems within the context of global climate warming, while the stringent implementation of ecological protection measures has collectively contributed to the enhancement of EQS. The proposed evaluation framework not only facilitates a comprehensive and precise assessment of regional EQS, but also provides a scientific basis for understanding and managing the adaptive responses of plateau ecosystems under the complex interplay of natural and anthropogenic factors.

Evaluation of the efficacy of polyethylene glycol in combination with different doses of linaclotide in a fractionated bowel preparation for colonoscopy: a prospective randomized controlled study.

BACKGROUND AND AIM: The ideal bowel cleansing program still needs to be explored. The aim was to compare the bowel cleansing effect and patient tolerance of low-dose polyethylene glycol (PEG) combined with different doses of linaclotide in fractionated bowel preparation. METHODS: The subjects were randomly assigned to the 3LPEG group, 2LPEG + 2L group, or 2LPEG + L group. The primary outcome was to use the Ottawa Bowel Preparation Scale (OBPS) to evaluate the efficacy of bowel cleansing, and the secondary outcomes were the detection rate of adenomas and polyps, adverse reactions, tolerance, and defecation dynamics; subsets of patients with chronic constipation and irritable bowel syndrome were also analyzed. RESULTS: A total of 753 patients were randomly assigned. In ITT analysis, the success of preparation of the 2LPEG + 2L group was better than that of the 2LPEG + L group or the 3LPEG group (92.0% vs. 82.3% vs. 82.1%; P = 0.002). Compared with the 3LPEG group, the 2LPEG + L group showed similar but non-inferior results (82.3% vs. 82.1%, P > 0.05). The 2LPEG + 2L group was similar to the 2LPEG + L group in terms of adverse reaction, tolerance, willingness to reuse, and sleep quality, but both were superior to the 3LPEG group. In a subgroup analysis of chronic constipation, the 2LPEG + 2L group had the best cleansing effect on the right colon and mid colon, while in the subgroup analysis of irritable bowel syndrome, the tolerance was better in the 2LPEG + 2L group and the 2LPEG + L group than the 3LPEG group. CONCLUSIONS: 2LPEG + 2L is a feasible bowel preparation regimen.

Prediction of synergistic gemcitabine-based combination treatment through a novel tumor stemness biomarker NANOG in pancreatic cancer.

Gemcitabine remains a first-class chemotherapeutic drug for pancreatic cancer. However, due to the rapid development of gemcitabine resistance in pancreatic cancer, gemcitabine alone or in combination with other anti-cancer drugs only showed limited effect in the clinic. It is extremely challenging to effectively and efficiently determine the optimal drug regimens. Thus, identification of appropriate prediction biomarkers is critical for the rational design of gemcitabine-based therapeutic options. Herein, a pancreatic cancer stem cell (PCSC) model exhibiting chemoresistance to gemcitabine was used to test the activity of clinical cancer drugs in the presence or absence of gemcitabine. As determined by combinatorial treatment, several types of drugs resensitized gemcitabine-resistant PCSCs to gemcitabine, with sorafenib (EGFR inhibitor)/gemcitabine and sunitinib (TBK1 inhibitors)/gemcitabine drug combinations being the most preferred treatments for PCSCs. Following the validation of the PCSC model by an antibody array test of 15-gene expression of stemness biomarkers, NANOG showed markedly different expression in PCSCs compared to the parental cells. From comprehensive analysis of stem cell index versus combination index, a stemness-related correlation model was successfully constructed to demonstrate the correlation between NANOG expression and synergism. Cancer cell stemness was ascertained to be highly relevant to NANOG overexpression that can be abrogated by synergized gemcitabine-drug combinations. Therefore, NANOG works as a therapeutic biomarker for predicating efficient combinatorial treatment of gemcitabine in pancreatic cancer.

Organic Matter Enrichment in Jurassic Hydrocarbon Source Rocks from the Turpan-Hami Basin: Insights from Organic and Elemental Geochemistry.

Petroleum can be generated by thermal cracking of organic matter within sediments, and the organic matter within sediments plays the dominant role in determining oil and gas generation. Organic matter within sediments is characterized by various sources, such as sapropelic organic matter from algal, microbial, and planktonic organisms and humic organic matter from higher plants. Paleo-productivity, terrestrial influx, and depositional environments could obviously influence the enrichment processes of the organic matter within sediments. Organic and elemental geochemical proxies can investigate the sedimentary process and reflect the enrichment characteristics of organic matter. In this study, hydrocarbon source rocks from the Shuixigou Group were collected from the Taibei Sag of the Turpan-Hami Basin, rock-eval pyrolysis was conducted, and stable carbon isotope composition of organic carbon and major and trace element distributions were measured. Based on this, the type and maturation of organic matter, paleo-productivity, terrestrial influx, and depositional paleo-environments were investigated. The results show that the Jurassic hydrocarbon source rocks are characterized by type III kerogen and are in the oil-window stage of maturation. The depositional paleo-environments of hydrocarbon source rocks in different formations are not remarkably different. The water bodies have freshwater oxidizing environments, and the paleo-climatic characteristics are warm and humid. However, the paleo-productivity of samples from the lower Jurassic Sangonghe Formation is higher than samples from other formations. Overall, the organic matter enrichment in Jurassic hydrocarbon source rocks of the Turpan-Hami Basin could be mutually controlled by the paleo-productivity and depositional paleo-environments. The results of this study could provide theoretical insight into deep petroleum exploration and resource evaluation in the Turpan-Hami Basin.

Flexible Temperature Sensor with High Reproducibility and Wireless Closed-Loop System for Decoupled Multimodal Health Monitoring and Personalized Thermoregulation.

Temperature and pulse waves are two fundamental indicators of body health. Specifically, thermoresistive flexible temperature sensors are one of the most applied sensors. However, they suffer from poor reproducibility of resistivity; and decoupling temperature from pressure/strain is still challenging. Besides, autonomous thermoregulation by wearable sensory systems is in high demand, but conventional commercial apparatuses are cumbersome and not suitable for long-term portable use. Here, a material-design strategy is developed to overcome the problem of poor reproducibility of resistivity by tuning the thermal expansion coefficient to nearly zero, precluding the detriment caused by shape expansion/shrinkage with temperature variation and achieving high reproducibility. The strategy also obtains more reliable sensitivity and higher stability, and the designed thermoresistive fiber has strain-insensitive sensing performance and fast response/recovery time. A smart textile woven by the thermoresistive fiber can decouple temperature and pulse without crosstalk; and a flexible wireless closed-loop system comprising the smart textile, a heating textile, a flexible diminutive control patch, and a smartphone is designed and constructed to monitor health status in real-time and autonomously regulate body temperature. This work offers a new route to circumvent temperature-sensitive effects for flexible sensors and new insights for personalized thermoregulation.