RG-I pectin-like polysaccharide from Rosa chinensis inhibits inflammation and fibrosis associated to HMGB1/TLR4/NF-κB signaling pathway to improve non-alcoholic steatohepatitis.

A novel RG-I pectin-like polysaccharide, YJ3A1, was purified from the flowers of Rosa chinensis and its structure and hepatoprotective effect in vivo and in vitro were investigated. The backbone of this polysaccharide is mainly composed of 1, 4-galactan, 1, 4-linked α-GalpA and 1, 2-linked α-Rhap disaccharide repeating unit attached by 1, 6-linked ß-Galp or 1, 5-linked α-Araf on C-4 of the Rhap. Interestingly, oral administration of YJ3A1 significantly ameliorates NASH-associated inflammation, oxidative stress and fibrosis and does not affect the liver morphology of normal mice at a dose of 50 mg/kg. The mechanism study suggests that the biological activity may associate to inactivating of high-mobility group box 1 protein (HMGB1)/TLR4/NF-κB and Akt signaling pathways by restraining the expression and release of HMGB1, thereby impeding the effect of NASH. The current findings outline a novel leading polysaccharide for new drug candidate development against NASH.

Precisely Controlling Polymer Acceptors with Weak Intramolecular Charge Transfer Effect and Superior Coplanarity for Efficient Indoor All-Polymer Solar Cells with over 27% Efficiency.

Indoor photovoltaics (IPVs) are garnering increasing attention from both the academic and industrial communities due to the pressing demand of the ecosystem of Internet-of-Things. All-polymer solar cells (all-PSCs), emerging as a sub-type of organic photovoltaics, with the merits of great film-forming properties, remarkable morphological and light stability, hold great promise to simultaneously achieve high efficiency and long-term operation in IPV's application. However, the dearth of polymer acceptors with medium-bandgap has impeded the rapid development of indoor all-PSCs. Herein, a highly efficient medium-bandgap polymer acceptor (PYFO-V) is reported through the synergistic effects of side chain engineering and linkage modulation and applied for indoor all-PSCs operation. As a result, the PM6:PYFO-V-based indoor all-PSC yields the highest efficiency of 27.1% under LED light condition, marking the highest value for reported binary indoor all-PSCs to date. More importantly, the blade-coated devices using non-halogenated solvent (o-xylene) maintain an efficiency of over 23%, demonstrating the potential for industry-scale fabrication. This work not only highlights the importance of fine-tuning intramolecular charge transfer effect and intrachain coplanarity in developing high-performance medium-bandgap polymer acceptors but also provides a highly efficient strategy for indoor all-PSC application.

Prevalence of Cardiovascular Conditions After Traumatic Brain Injury: A Comparison Between the Traumatic Brain Injury Model Systems and the National Health and Nutrition Examination Survey.

BACKGROUND: The purpose of this study is to compare the prevalence of self-reported cardiovascular conditions among individuals with moderate to severe traumatic brain injury (TBI) to a propensity-matched control cohort. METHODS AND RESULTS: A cross-sectional study described self-reported cardiovascular conditions (hypertension, congestive heart failure [CHF], myocardial infarction [MI], and stroke) from participants who completed interviews between January 2015 and March 2020 in 2 harmonized large cohort studies, the TBI Model Systems and the National Health and Nutrition Examination Survey. Mixed-effect logistic regression models were used to compare the prevalence of cardiovascular conditions after 1:1 propensity-score matching based on age, sex, race, ethnicity, body mass index, education level, and smoking status. The final sample was 4690 matched pairs. Individuals with TBI were more likely to report hypertension (odds ratio [OR], 1.18 [95% CI, 1.08-1.28]) and stroke (OR, 1.70 [95% CI, 1.56-1.98]) but less likely to report CHF (OR, 0.81 [95% CI, 0.67-0.99]) or MI (OR, 0.66 [95% CI, 0.55-0.79]). There was no difference in rate of CHF or MI for those ≤50 years old; however, rates of CHF and MI were lower in the TBI group for individuals >50 years old. Over 65% of individuals who died before the first follow-up interview at 1 year post-TBI were >50 years old, and those >50 years old were more likely to die of heart disease than those ≤50 years old (17.6% versus 8.6%). CONCLUSIONS: Individuals with moderate to severe TBI had an increased rate of self-reported hypertension and stroke but lower rate of MI and CHF than uninjured adults, which may be due to survival bias.

Climate change intensifies algal biomass resurgence in eutrophic Lake Taihu, China.

Climate change can significantly alter phytoplankton growth and proliferation, which would counteract restoration efforts to control algal blooms. However, the knowledge is limited about the quantitative evaluation of the causal effect of algal biomass resurgence in large shallow lakes where there is no significant improvement after long term lake restoration. Here, a bucket process-based phytoplankton dynamic model is developed to quantify the contributions of climate change and nutrients concentration changes to phytoplankton biomass resurgence after 2014 in hypereutrophic Lake Taihu, China. Compared to 2008-2014, the mean water temperature (WT) and the mean phosphate are higher, the mean photosynthetically active radiation (PAR), the mean total suspended solids (TSS), and the mean dissolved inorganic nitrogen (DIN) are lower, during 2015-2020. Their contribution to algal biomass resurgence during 2015-2020 is WT (+58.7 %), PAR (-2.6 %), TSS (+23.2 %), DIN (-22.1 %) and phosphate (+42.7 %), respectively. Climate change (WT, PAR, and TSS), which contributed +64.9 % to the phytoplankton biomass resurgence, underscores the urgent need to continuously take more effective measures to reduce nutrient emissions to offset the effects of climate change in Lake Taihu and in other eutrophic lakes.

Optimized Incorporation of Furan into Diketopyrrolopyrrole-Based Conjugated Polymers for Organic Field-Effect Transistors.

Flexible electronics have received considerable attention in the past decades due to their promising application in rollable display screens, wearable devices, implantable devices, and other electronic applications. In particular, conjugated polymers are favored for flexible electronics due to their mechanical flexibility and potential for solution-processed fabrication techniques, such as blade-coating, roll-to-roll printing, and high-throughput printing allowing for high-performance transistor devices. Thiophene is the prevailing conjugated unit to construct these conjugated polymers due to its favorable electronic properties. On the other hand, furans are among the few conjugated moieties that are easily derived from bio renewable resources. To promote sustainability, we selectively introduced furan into the conjugated backbone of a high-mobility polymer scaffold and systematically studied the effect on the microstructure and charge transport. We show that partially and selectively replacing thiophene units with furan can yield nearly comparable performance compared to the all-thiophene polymer. This strategy offers an improvement in the sustainability of the polymer by incorporating bio-sourced furan without sacrificing the high-performance characteristics. Meanwhile, polymers with incorrect or complete furan incorporation show reduced mobilities. This work serves to develop coherent structure-morphology-performance relationships; such knowledge will establish guidelines for the future development of sustainable, furan-based conjugated materials.

Stereo-electroencephalographic seizure localization in patients with mesial temporal sclerosis: A single center experience.

Objective: Epilepsy patients with mesial temporal sclerosis (MTS) on imaging who are drug-resistant usually undergo epilepsy surgery without previous invasive evaluation. However, up to one-third of patients are not seizure-free after surgery. Prior studies have identified risk factors for surgical failure, but it is unclear if they are associated with bilateral or discordant seizure onset. Methods: In this retrospective case series, we identified 17 epilepsy patients who had MRI-confirmed MTS but received invasive stereo-EEG (SEEG) evaluation before definitive intervention. We analyzed their presurgical risk factors in relation to SEEG seizure onset localization and MRI/SEEG concordance. Results: SEEG ictal onset was concordant with MTS localization (i.e. seizures started only from the hippocampus with MTS) in 5 out of 13 patients with unilateral MTS (UMTS) and in 3 out of 4 patients with bilateral MTS.No statistically significant association regarding concordance of SEEG ictal onset and MTS location was found in patients with such risk factors as a history of non-mesial temporal aura, frequent focal to bilateral tonic-clonic seizures, prior viral brain infection, or family history of epilepsy. Nine out of 13 UMTS patients had resective surgery only, 5 out of 9 (56 %) have Engel class I outcome at most recent follow-up (median 46.5 months, range 22-91 months). In Engel class I cohort, the SEEG ictal onset was concordant with MTS location in 3 out of 5 patients, and 2 patients had ipsilateral temporal neocortical ictal onset. Conclusions: Our findings suggest that patients with MTS might have discordant SEEG ictal onset (in 61.5% patients with UMTS in presented cohort), which may explain poor surgical outcome after destructive surgery in these cases. Significance: Although no statistically significant association was found in this under-powered study, these findings could be potentially valuable for future meta-analyses.

Community-based exercise program, self-reported health-related symptoms, and quality of life in persons with traumatic brain injury 45 + years old.

BACKGROUND: Individuals with moderate to severe traumatic brain injury (msTBI) have reported a lack of motivation, lack of time, and fatigue as perceived barriers to exercise. OBJECTIVE: To evaluate the effects of an exercise program on self-reported health-related symptoms and quality of life in persons 45-years and older with msTBI. METHODS: Post-hoc analysis of a prospective community-based 12-week exercise program of 20 adults, age 45-80 years, with msTBI. Ten were in aerobic exercise training (AET) program and 10 in a stretching and toning (SAT) program. The AET group was instructed to exercise based on their estimated maximal heart rate (HR) for 150 minutes weekly. The SAT group was to stretch for the same target time without significantly increasing HR or level of exertion. Outcome measures were Traumatic Brain Injury Quality of Life (TBI-QOL) for global, cognitive, emotional, and social health, Patient Health Questionnaire-9 (PHQ-9) for depressive symptoms, and Pittsburgh Sleep Quality Index (PSQI) for sleep quality. RESULTS: AET was associated with improved self-reported cognitive health and sleep compared to SAT. Moderate to large, positive effect sizes were also observed in the AET group in the QOL categories of global, emotional, and social health, and depressive symptoms. CONCLUSIONS: This study offers preliminary evidence that AET may improve health-related QOL, especially for cognition and sleep, in middle-aged and older adults with msTBI.

The role of interfacial donor-acceptor percolation in efficient and stable all-polymer solar cells.

Polymerization of Y6-type acceptor molecules leads to bulk-heterojunction organic solar cells with both high power-conversion efficiency and device stability, but the underlying mechanism remains unclear. Here we show that the exciton recombination dynamics of polymerized Y6-type acceptors (Y6-PAs) strongly depends on the degree of aggregation. While the fast exciton recombination rate in aggregated Y6-PA competes with electron-hole separation at the donor-acceptor (D-A) interface, the much-suppressed exciton recombination rate in dispersed Y6-PA is sufficient to allow efficient free charge generation. Indeed, our experimental results and theoretical simulations reveal that Y6-PAs have larger miscibility with the donor polymer than Y6-type small molecular acceptors, leading to D-A percolation that effectively prevents the formation of Y6-PA aggregates at the interface. Besides enabling high charge generation efficiency, the interfacial D-A percolation also improves the thermodynamic stability of the blend morphology, as evident by the reduced device "burn-in" loss upon solar illumination.

Real-Time Seizure Detection Using Behind-the-Ear Wearable System.

INTRODUCTION: This study examines the usability and comfort of a behind-the-ear seizure detection device called brain seizure detection (BrainSD) that captures ictal electroencephalogram (EEG) data using four scalp electrodes. METHODS: This is a feasibility study. Thirty-two patients admitted to a level 4 Epilepsy Monitoring Unit were enrolled. The subjects wore BrainSD and the standard 21-channel video-EEG simultaneously. Epileptologists analyzed the EEG signals collected by BrainSD and validated it using video-EEG data to confirm its accuracy. A poststudy survey was completed by each participant to evaluate the comfort and usability of the device. In addition, a focus group of UT Southwestern epileptologists was held to discuss the features they would like to see in a home EEG-based seizure detection device such as BrainSD. RESULTS: In total, BrainSD captured 11 of the 14 seizures that occurred while the device was being worn. All 11 seizures captured on BrainSD had focal onset, with three becoming bilateral tonic-clonic and one seizure being of subclinical status. The device was worn for an average of 41 hours. The poststudy survey showed that most users found the device comfortable, easy-to-use, and stated they would be interested in using BrainSD. Epileptologists in the focus group expressed a similar interest in BrainSD. CONCLUSIONS: Brain seizure detection is able to detect EEG signals using four behind-the-ear electrodes. Its comfort, ease-of-use, and ability to detect numerous types of seizures make BrainSD an acceptable at-home EEG detection device from both the patient and provider perspective.

Functional structural domain synthesis of anti-pancreatic carcinoma pectin-like polysaccharide RN1.

The great structural and functional diversity supports polysaccharides as favorable candidates for new drug development. Previously we reported that a drug candidate pectin-like natural polysaccharide, RN1 might target galectin-3 (Gal-3) to impede pancreatic cancer cell growth in vivo. However, the quality control of polysaccharide-based drug research faces great challenges due to the heterogeneity. A potential solution is to synthesize structurally identified subfragments of this polysaccharide as alternatives. In this work, we took RN1 as an example, and synthesized five subfragments derived from the putative repeating units of RN1. Among them, pentasaccharide 4 showed an approximative binding affinity to Gal-3 in vitro, as well as an antiproliferative activity against pancreatic BxPC-3 cells comparable to that of RN1. Further, we scaled up pentasaccharide 4 to gram-scale in an efficient synthetic route with a 6.9 % yield from D-galactose. Importantly, pentasaccharide 4 significantly suppressed the growth of pancreatic tumor in vivo. Based on the mechanism complementarity of galactin-3 inhibitor and docetaxel, the combination administration of pentasaccharide 4 and docetaxel afforded better result. The result suggested pentasaccharide 4 was one of the functional structural domains of polysaccharide RN1 and might be a leading compound for anti-pancreatic cancer new drug development.

Inulin-like polysaccharide ABWW may impede CCl4 induced hepatic stellate cell activation through mediating the FAK/PI3K/AKT signaling pathway in vitro & in vivo.

Studies have shown that terrestrial acidic polysaccharides containing carboxyl groups and seaweed sulfated polysaccharides have strong potential in anti-liver fibrosis. However, there is no investigation on the anti-liver fibrosis of fructan, a ubiquitous natural polysaccharide. The present study aimed to understand the effect of fructan in ameliorating carbon tetrachloride (CCl4)-induced liver fibrosis in mice. Here, an inulin-like fructan ABWW from Achyranthes bidentata Bl. was characterized by fructose enzymatic hydrolysis, methylation analysis, ESI-MS, and NMR. It was composed of →2)-ß-d-Fruf-(1→ and →2)-ß-d-Fruf-(1, 6→, terminated with →1)-α-d-Glcp and →2)-ß-d-Fruf residues. The biological studies showed that ABWW could improve liver damage and liver fibrosis induced by CCl4in vivo and inhibit hepatic stellate cell (HSC) activation and migration in vitro. We further demonstrated that ABWW inhibited LX2 activation via suppressing the FAK/PI3K/AKT signaling pathway. Hence, ABWW might be a potential novel active compound for anti-fibrosis new drug development.

Age-related smartphone use patterns among individuals with moderate-to-severe traumatic brain injury.

OBJECTIVE: With mobile health technologies serving as an alternative means of providing healthcare, evaluating patients' abilities to navigate digital infrastructures is becoming increasingly relevant. The goal of this study is to investigate smartphone use patterns among individuals with history of moderate-to-severe traumatic brain injury (TBI). METHODS: An anonymous survey was delivered via e-mail or text message to eligible participants who had a history of moderate-to-severe TBI and were prospectively followed at one of the eight participating Traumatic Brain Injury Model Systems centers for at least 1-year post-injury. The survey captured demographic data and included a questionnaire to evaluate smartphone use (calling, texting, web browsing, etc.). RESULTS: A total of 2665 eligible individuals were contacted to complete the survey, 472 of which responded. 441 of them reported smartphone use. Individuals ages 45 and older were significantly less likely to use their phones for functions other than calling and texting when compared to individuals ages 18-44 (p < 0.05). CONCLUSIONS: Most individuals with moderate-to-severe TBI in this cohort demonstrated intentional smartphone use, suggesting that mobile health technologies may be feasible as a cost-effective healthcare alternative. However, doing so will require additional interventions to provide further technological education especially in older individuals with TBI.

Precise synthesis and photovoltaic properties of giant molecule acceptors.

Series of giant molecule acceptors DY, TY and QY with two, three and four small molecule acceptor subunits are synthesized by a stepwise synthetic method and used for systematically investigating the influence of subunit numbers on the structure-property relationship from small molecule acceptor YDT to giant molecule acceptors and to polymerized small molecule acceptor PY-IT. Among these acceptors-based devices, the TY-based film shows proper donor/acceptor phase separation, higher charge transfer state yield and longer charge transfer state lifetime. Combining with the highest electron mobility, more efficient exciton dissociation and lower charge carrier recombination properties, the TY-based device exhibits the highest power conversion efficiency of 16.32%. These results indicate that the subunit number in these acceptors has significant influence on their photovoltaic properties. This stepwise synthetic method of giant molecule acceptors will be beneficial to diversify their structures and promote their applications in high-efficiency and stable organic solar cells.

Chemical approaches for the stereocontrolled synthesis of 1,2-cis-ß-D-rhamnosides.

In carbohydrate chemistry, the stereoselective synthesis of 1,2-cis-glycosides remains a formidable challenge. This complexity is comparable to the synthesis of 1,2-cis-ß-D-mannosides, primarily due to the adverse anomeric and Δ-2 effects. Over the past decades, to attain ß-stereoselectivity in D-rhamnosylation, researchers have devised numerous direct and indirect methodologies, including the hydrogen-bond-mediated aglycone delivery (HAD) method, the synthesis of ß-D-mannoside paired with C6 deoxygenation, and the combined approach of 1,2-trans-glycosylation and C2 epimerization. This review elaborates on the advancements in ß-D-rhamnosylation and its implications for the total synthesis of tiacumicin B and other physiologically relevant glycans.

Plasma von Willebrand Factor Is Elevated Hyperacutely After Mild Traumatic Brain Injury.

Each year in the United States, ∼2.7 million persons seek medical attention for traumatic brain injury (TBI), of which ∼85% are characterized as being mild brain injuries. Many different cell types in the brain are affected in these heterogeneous injuries, including neurons, glia, and the brain vasculature. Efforts to identify biomarkers that reflect the injury of these different cell types have been a focus of ongoing investigation. We hypothesized that von Willebrand factor (vWF) is a sensitive biomarker for acute traumatic vascular injury and correlates with symptom severity post-TBI. To address this, blood was collected from professional boxing athletes (n = 17) before and within 30 min after competition. Plasma levels of vWF and neuron-specific enolase were measured using the Meso Scale Discovery, LLC. (MSD) electrochemiluminescence array-based multi-plex format (MSD, Gaithersburg, MD). Additional symptom and outcome data from boxers and patients, such as the Rivermead symptom scores (Rivermead Post Concussion Symptoms Questionnaire [RPQ-3]), were collected. We found that, subsequent to boxing bouts, there was a 1.8-fold increase in vWF levels within 30 min of injury (p < 0.0009). Moreover, fold-change in vWF correlates moderately (r = 0.51; p = 0.03) with the number of head blows. We also found a positive correlation (r = 0.69; p = 0.002) between fold-change in vWF and self-reported post-concussive symptoms, measured by the RPQ-3. The receiver operating curve analysis of vWF plasma levels and RPQ-3 scoring yielded a sensitivity of 94.12% and a specificity of 76.5% with an area under the curve of 83% for boxers after a fight compared to the pre-bout baseline. This study suggests that vWF is a potential blood biomarker measurable in the hyperacute period after blunt mild TBI. This biomarker may prove to be useful in diagnosing and monitoring traumatic vascular injury.

Selective activator of human ClpP triggers cell cycle arrest to inhibit lung squamous cell carcinoma.

Chemo-activation of mitochondrial ClpP exhibits promising anticancer properties. However, we are currently unaware of any studies using selective and potent ClpP activators in lung squamous cell carcinoma. In this work, we report on such an activator, ZK53, which exhibits therapeutic effects on lung squamous cell carcinoma in vivo. The crystal structure of ZK53/ClpP complex reveals a π-π stacking effect that is essential for ligand binding selectively to the mitochondrial ClpP. ZK53 features on a simple scaffold, which is distinct from the activators with rigid scaffolds, such as acyldepsipeptides and imipridones. ZK53 treatment causes a decrease of the electron transport chain in a ClpP-dependent manner, which results in declined oxidative phosphorylation and ATP production in lung tumor cells. Mechanistically, ZK53 inhibits the adenoviral early region 2 binding factor targets and activates the ataxia-telangiectasia mutated-mediated DNA damage response, eventually triggering cell cycle arrest. Lastly, ZK53 exhibits therapeutic effects on lung squamous cell carcinoma cells in xenograft and autochthonous mouse models.

Auxiliary sequential deposition enables 19%-efficiency organic solar cells processed from halogen-free solvents.

High-efficiency organic solar cells are often achieved using toxic halogenated solvents and additives that are constrained in organic solar cells industry. Therefore, it is important to develop materials or processing methods that enabled highly efficient organic solar cells processed by halogen free solvents. In this paper, we report an innovative processing method named auxiliary sequential deposition that enables 19%-efficiency organic solar cells processed by halogen free solvents. Our auxiliary sequential deposition method is different from the conventional blend casting or sequential deposition methods in that it involves an additional casting of dithieno[3,2-b:2',3'-d]thiophene between the sequential depositions of the donor (D18-Cl) and acceptor (L8-BO) layers. The auxiliary sequential deposition method enables dramatic performance enhancement from 15% to over 18% compared to the blend casting and sequential deposition methods. Furthermore, by incorporating a branched-chain-engineered acceptor called L8-BO-X, device performance can be boosted to over 19% due to increased intermolecular packing, representing top-tier values for green-solvent processed organic solar cells. Comprehensive morphological and time-resolved characterizations reveal that the superior blend morphology achieved through the auxiliary sequential deposition method promotes charge generation while simultaneously suppressing charge recombination. This research underscores the potential of the auxiliary sequential deposition method for fabricating highly efficient organic solar cells using environmentally friendly solvents.

Src is a target molecule of mannose against pancreatic cancer cells growth in vitro & in vivo.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant cancer with limited treatment options. Mannose, a common monosaccharide taken up by cells through the same transporters as glucose, has been shown to induce growth retardation and enhance cell death in response to chemotherapy in several cancers, including PDAC. However, the molecular targets and mechanisms underlying mannose's action against PDAC are not well understood. In this study, we used an integrative approach of network pharmacology, bioinformatics analysis, and experimental verification to investigate the pharmacological targets and mechanisms of mannose against PDAC. Our results showed that the protein Src is a key target of mannose in PDAC. Additionally, computational analysis revealed that mannose is a highly soluble compound that meets Lipinski's rule of five and that the expression of its target molecules is correlated with survival rates and prognosis in PDAC patients. Finally, we validated our findings through in vitro and in vivo experiments. In conclusion, our study provides evidence that mannose plays a critical role in inhibiting PDAC growth by targeting Src, suggesting that it may be a promising therapeutic candidate for PDAC.

A pectic polysaccharide isolated from Achyranthes bidentata is metabolized by human gut Bacteroides spp.

Achyranthes bidentata (A. bidentata) is a famous traditional Chinese medicine (TGM) for treatment osteoporosis. Polysaccharides, a major factor for shaping the gut microbiota, are the primary ingredients of A. bidentata. However, bioactivity of A. bidentata polysaccharide on human gut microbiota (HGM) remains unknown. Here, a homogeneous pectic polysaccharide A23-1 with average molecular weight of 93.085 kDa was extracted and purified from A. bidentata. And A23-1 was compsed of rhamnose, glucuronic acid, galacturonic acid, glucose, galactose and arabinose in a molar ratio of 7.26: 0.76: 5.12: 2.54: 23.51: 60.81. GC-MS, partial acid hydrolysis and NMR results indicated the backbone of A23-1 was composed of 1, 2, 4-Rhap and 1, 4-GlapA, while the branches were composed of galactose, arabinose, glucose and glucuronic acid. Further, A23-1 was found to be degraded into monosaccharides and fragments. Taking Bacteroides thetaiotaomicron (BT) as a model, we suggested three polysaccharide utilization loci (PULs) might be involved in the A23-1 degradation. Degraded products generated by BO might not support the growth of probiotics. Besides, acetate and propionate as the main end products were generated by Bacteroides spp. and probiotics utilizing A23-1. These findings suggested A23-1 was possible one of food sources of human gut Bacteroides spp.