Toward a neurocircuit-based sequential transcranial magnetic stimulation treatment of pediatric bipolar II disorder.

BACKGROUND: Abnormalities in large-scale neuronal networks-the frontoparietal central executive network (CEN)-are consistent findings in bipolar disorder and potential therapeutic targets for transcranial magnetic stimulation (TMS). OBJECTIVE: The present study aimed to assess the effects of CEN neurocircuit-based sequential TMS on the clinical symptoms and cognitive functions of adolescents with bipolar II disorder. METHODS: The study was a single-blinded, randomized, placebo-control trial. Participants with DSM-5-defined bipolar disorder II were recruited and randomized to receive either a sham treatment (n = 20) or an active TMS treatment (n = 22). The active group patients were taking medication, with intermittent theta burst stimulation (iTBS) treatment provided as adjunctive treatment targeting the left DLPFC, the left ITG, and the left PPC nodes consecutively. Patients completed the measurements of HAMD and the Das-Naglieri Cognition Assessment System at baseline and 3 weeks after the intervention. RESULTS: A significant group-by-time interaction was observed in the HAMD, total cognition, and planning. Post-hoc analysis revealed that patients in the active group significantly improved HAMD scores following neurostimulation. Moreover, within-subject analysis indicated that the active group significantly improved in scores of total cognition and planning, while the sham group did not. No significant differences were seen in the other cognitive measures. CONCLUSION: The neurocircuit-based sequential TMS protocol targeting three CEN nodes, in conjunction with medication, safely and effectively improved depressive symptoms and cognitive function in adolescents with bipolar II disorder.

Expression levels and clinical significance of serum miR-19a/CCL20 in patients with acute cerebral infarction.

Acute cerebral infarction (ACI) is a lethal disease whose early diagnosis is critical for treatment. microRNA (miR)-19a targets CC chemokine ligand 20 (CCL20) in myocardial infarction. We investigated the expression patterns of serum miR-19a and CCL20 of ACI patients and assessed their clinical values. Serum samples of 50 healthy subjects and110 ACI patients were collected. Serum levels of miR-19a, CCL20 mRNA, and biochemical indexes were assessed. miR-19a downstream target gene and the binding relationship between miR-19a and CCL20 were predicted and verified. miR-19a and CCL20 mRNA were subjected to correlation and diagnostic efficiency analysis. miR-19a was poorly expressed in the serum of ACI patients, especially in patients with unstable plaque and large infarction. tumor necrosis factor-α, low-density lipoprotein, and platelet/lymphocyte ratio negatively correlated with serum miR-19a level and positively correlated with CCL20. Dual-luciferase assay revealed that miR-19a could negatively regulate CCL20 expression. CCL20 was highly expressed in the serum of ACI patients. The area under receiver-operating characteristic curve of miR-19a combined with CCL20 was 0.9741 (98.00% specificity, 90.91% sensitivity), higher than their single diagnosis. Collectively, miR-19a had high diagnostic value for ACI and could target to restrain CCL20. The combination of miR-19a and CCL20 improved diagnostic value for ACI.

A Survey on Nutrition Labeling for Sodium, Potassium, and Phosphorus of Packaged Food and Beverages.

OBJECTIVES: Nutrition labeling is important to guide patients with chronic kidney disease to make informed choices. This study aimed to evaluate the extent and accessibility of nutrition labeling for sodium, potassium, and phosphorus on food and beverage products in a supermarket. METHODS: A cross-sectional survey was conducted in a Malaysian supermarket. Information on sodium, potassium, and phosphorus contents was collected from the nutrition fact panel, while information on food additives containing sodium, potassium, and phosphorus was collected from the ingredient list. RESULTS: The survey included 2,577 foods and beverages, and 79.4% of the products included sodium information in nutrition fact panels, but only 11.7% and 2.0% disclosed potassium and phosphorus content, respectively. Sodium-containing additives were found in 78.6% of products; potassium- and phosphorus-containing additives were reported in 28.5% and 46.9% of products, respectively. Sodium-containing additives were typically listed as "salt," potassium-containing additives as "alternative names," and phosphorus-containing additives as "starch" and "E numbers." Imported products were more likely to include sodium (P < .001) and phosphorus (p = .036) contents, while more locally manufactured products reported sodium- (p = .003) and phosphorus- (P = .004) containing additives. CONCLUSION: There is limited availability of potassium and phosphorus information on nutrition labels in Malaysia food and beverage products, which presents significant challenges for individuals with chronic kidney disease in choosing appropriate products for their dietary needs.

NR4A1 transcriptionally regulates the differentiation of stem-like CD8+ T cells in the tumor microenvironment.

CD8+ T cells are rendered exhausted in tumor and chronic infection. Among heterogeneous exhausted T cells, a subpopulation of progenitor-like (Tpex) cells have been found important for long-term tumor or pathogen control and are also the main responders in immunotherapy. Using an RFP reporter mouse for the orphan nuclear receptor NR4A1, originally characterized as critical in T cell dysfunction, we discover that the reporter is highly expressed in Tpex cells in tumor and chronic infection. Enforced expression of Nr4a1 promotes Tpex cell accumulation, whereas tumor control is improved after Nr4a1 deletion, associated with increased effector function but decreased long-term maintenance of CD8+ T cells. Integrating chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) analysis, NR4A1 is found to bind and promote the expression of Tpex-related genes, as well as suppress terminal differentiation-associated genes. This study therefore has identified a key role of NR4A1 in Tpex regulation and provides a promising target for immunotherapy.

Sulforaphane decreases oxidative stress and inhibits NLRP3 inflammasome activation in a mouse model of ulcerative colitis.

Excessive oxidative stress and NLRP3 inflammasome activation are considered the main drivers of inflammatory bowel disease (IBD), and inhibition of inflammasomes ameliorates clinical symptoms and morphological manifestations of IBD. Herein, we examined the roles of NLRP3 activation in IBD and modulation of NLRP3 by sulforaphane (SFN), a compound with multiple pharmacological activities that is extracted from cruciferous plants. To simulate human IBD, we established a mouse colitis model by administering dextran sodium sulfate in the drinking water. SFN (25, 50 mg·kg-1·d-1, ig) or the positive control sulfasalazine (500 mg/kg, ig) was administered to colitis-affected mice for 7 days. Model mice displayed pathological alterations in colon tissue as well as classic symptoms of colitis beyond substantial tissue inflammation. Expression of NLRP3, ASC, and caspase-1 was significantly elevated in the colonic epithelium. The expression of NLRP3 inflammasomes led to activation of downstream proteins and increases in the cytokines IL-18 and IL-1ß. SFN administration either fully or partially reversed these changes, thus restoring IL-18 and IL-1ß, substantially inhibiting NLRP3 activation, and decreasing inflammation. SFN alleviated the inflammation induced by LPS and NLRP3 agonists in RAW264.7 cells by decreasing the levels of reactive oxygen species. In summary, our results revealed the pathological roles of oxidative stress and NLRP3 in colitis, and indicated that SFN might serve as a natural NLRP3 inhibitor, thereby providing a new strategy for alternative colitis treatment.

A target-triggered strand displacement-assisted target recycling based on carbon dots-based fluorescent probe and MSNs@PDA nanoparticles for miRNA amplified detection and fluorescence imaging.

A target-triggered strand displacement-assisted target recycling based on carbon dots-based fluorescent probe and mesoporous silica nanoparticles@polydopamine (MSNs@PDA) was established to detect miRNA. The surface of MSNs rich in mesopores was coated with a layer of PDA, which can adsorb and quench the fluorescence of single-stranded Fuel DNA with fluorescent carbon dots (CDs) modified at the end through fluorescence resonance energy transfer (FRET). After adding double-stranded DNA-gold nanoparticles (dsDNA-AuNPs) and target let-7a, it will trigger two toehold-mediated strand displacement reactions (TSDR), leading to the recovery of fluorescence and the recycling of target let-7a (excitation wavelength: 380 nm; emission wavelength: 458 nm). The recovery value of fluorescence is proportional to the logarithm of the target microRNA let-7a concentration, thus realizing the sensitivity amplification detection of disease markers. The MSNs@PDA@Fuel DNA-CDs/dsDNA-AuNPs nanoplatform based on the strategy of "on-off-on" and TSDR cyclic amplification may hold great potential as an effective and safe nanoprobe for accurate fluorescence imaging of diseases related to miRNA with low abundances.

The combined toxicity of polystyrene nano/micro-plastics and triphenyl phosphate (TPHP) on HepG2 cells.

Combined toxicity is a critical concern during the risk assessment of environmental pollutants. Due to the characteristics of strong hydrophobicity and large specific surface area, microplastics (MPs) and nanoplastics (NPs) have become potential carriers of organic pollutants that may pose a health risk to humans. The co-occurrence of organic pollutants and MPs would cause adverse effects on aquatic organism, while the information about combined toxicity induced by organophosphorus flame retardants and MPs on human cells was limited. This study aimed to reveal the toxicity effects of co-exposure to triphenyl phosphate (TPHP) and polystyrene (PS) particles with micron-size/nano-size on HepG2 cell line. The adsorption behaviors of TPHP on PS particles was observed, with the PS-NP exhibiting a higher adsorption capacity. The reactive oxygen species generation, mitochondrial membrane potential depolarization, lactate dehydrogenase release and cell apoptosis proved that PS-NPs/MPs exacerbated TPHP-induced cytotoxicity. The particle size of PS would affect the toxicity to HepG2 cells that PS-NP (0.07 µm) exhibited more pronounced combined toxicity than PS-MP (1 µm) with equivalent concentrations of TPHP. This study provides fundamental insights into the co-toxicity of TPHP and PS micro/nanoplastics in HepG2 cells, which is crucial for validating the potential risk of combined toxicity in humans.

Custom-tailored hole transport layer using oxalic acid for high-quality tin-lead perovskites and efficient all-perovskite tandems.

All-perovskite tandem solar cells (TSCs) have exhibited higher efficiencies than single-junction perovskite solar cells (PSCs) but still suffer from the unsatisfactory performance of low-bandgap (LBG) tin-lead (Sn-Pb) subcells. The inherent properties of PEDOT:PSS are crucial to high-performance Sn-Pb perovskite films and devices; however, the underlying mechanism has not been fully explored and revealed. Here, we report a facile oxalic acid treatment of PEDOT:PSS (OA-PEDOT:PSS) to precisely regulate its work function and surface morphology. OA-PEDOT:PSS shows a larger work function and an ordered reorientation and fiber-shaped film morphology with efficient hole transport pathways, leading to the formation of more ideal hole-selective contact with Sn-Pb perovskite for suppressing interfacial nonradiative recombination losses. Moreover, OA-PEDOT:PSS induces (100) preferred orientation growth of perovskite for higher-quality Sn-Pb films. Last, the OA-PEDOT:PSS-tailored LBG PSC yields an impressive efficiency of up to 22.56% (certified 21.88%), enabling 27.81% efficient all-perovskite TSC with enhanced operational stability.

Anterior cingulate cortex projections to the dorsal medial striatum underlie insomnia associated with chronic pain.

Chronic pain often leads to the development of sleep disturbances. However, the precise neural circuit mechanisms responsible for sleep disorders in chronic pain have remained largely unknown. Here, we present compelling evidence that hyperactivity of pyramidal neurons (PNs) in the anterior cingulate cortex (ACC) drives insomnia in a mouse model of nerve-injury-induced chronic pain. After nerve injury, ACC PNs displayed spontaneous hyperactivity selectively in periods of insomnia. We then show that ACC PNs were both necessary for developing chronic-pain-induced insomnia and sufficient to mimic sleep loss in naive mice. Importantly, combining optogenetics and electrophysiological recordings, we found that the ACC projection to the dorsal medial striatum (DMS) underlies chronic-pain-induced insomnia through enhanced activity and plasticity of ACC-DMS dopamine D1R neuron synapses. Our findings shed light on the pivotal role of ACC PNs in developing chronic-pain-induced sleep disorders.

Ligand-free Pd-catalyzed highly selective arylation of activated and unactivated alkenes via oxidative and reductive heck coupling.

In this work, an eco-friendly, green, efficient approach for oxidative and reductive Heck-Mizoroki (HM) reactions was developed, which offered acceptable yields from first-pass experiments. Mono-arylation was achieved without the use of ligands, directing groups, or prefunctionalized alkenes. Considering mild reaction conditions, good functional group compatibility, and great regioselectivity, the method can find broad applications in novel medicine and material development and discovery processes.

Enantioselective Total Synthesis of (-)-Daphenylline.

A concise enantioselective total synthesis of (-)-daphenylline, a hexacyclic Daphniphyllum alkaloid with a unique benzene ring, was achieved in 14 steps. The synthesis commences with two chiral stereocenters, C2 and C18, readily installed via Carreira's Ir/amine dual-catalyzed allylation. The allylic bridgehead amine 6 was rapidly prepared through Wickens' photoredox-catalyzed hydrocarboxylation of olefin and CuBr2-catalyzed α-amination of ketone. The tetracycle 4 was formed via Pd-catalyzed reductive Heck reaction or, more concisely, by Krische's Rh-catalyzed reductive 1,6-enyne cyclization. In this synthesis, newly reported Wickens' photoredox-catalyzed hydrocarboxylation was used twice, and Friedel-Crafts acylation thrice.

Class-Incremental Unsupervised Domain Adaptation via Pseudo-Label Distillation.

Class-Incremental Unsupervised Domain Adaptation (CI-UDA) requires the model can continually learn several steps containing unlabeled target domain samples, while the source-labeled dataset is available all the time. The key to tackling CI-UDA problem is to transfer domain-invariant knowledge from the source domain to the target domain, and preserve the knowledge of the previous steps in the continual adaptation process. However, existing methods introduce much biased source knowledge for the current step, causing negative transfer and unsatisfying performance. To tackle these problems, we propose a novel CI-UDA method named Pseudo-Label Distillation Continual Adaptation (PLDCA). We design Pseudo-Label Distillation module to leverage the discriminative information of the target domain to filter the biased knowledge at the class- and instance-level. In addition, Contrastive Alignment is proposed to reduce domain discrepancy by aligning the class-level feature representation of the confident target samples and the source domain, and exploit the robust feature representation of the unconfident target samples at the instance-level. Extensive experiments demonstrate the effectiveness and superiority of PLDCA. Code is available at code.

Optimizing ZnO-Quantum Dot Interface with Thiol as Ligand Modification for High-Performance Quantum Dot Light-Emitting Diodes.

As the electron transport layer in quantum dot light-emitting diodes (QLEDs), ZnO suffers from excessive electrons that lead to luminescence quenching of the quantum dots (QDs) and charge-imbalance in QLEDs. Therefore, the interplay between ZnO and QDs requires an in-depth understanding. In this study, DFT and COSMOSL simulations are employed to investigate the effect of sulfur atoms on ZnO. Based on the simulations, thiol ligands (specifically 2-hydroxy-1-ethanethiol) to modify the ZnO nanocrystals are adopted. This modification alleviates the excess electrons without causing any additional issues in the charge injection in QLEDs. This modification strategy proves to be effective in improving the performance of red-emitting QLEDs, achieving an external quantum efficiency of over 23% and a remarkably long lifetime T95 of >12 000 h at 1000 cd m-2. Importantly, the relationship between ZnO layers with different electronic properties and their effect on the adjacent QDs through a single QD measurement is investigated. These findings show that the ZnO surface defects and electronic properties can significantly impact the device performance, highlighting the importance of optimizing the ZnO-QD interface, and showcasing a promising ligand strategy for the development of highly efficient QLEDs.

Physiological and Pathological Roles of NTSR2 in Several Organs and Diseases (Review).

Neurotensin (NTS) and its receptors (NTSRs) have long been the subject of study and have shown to have a vital function in a variety of systems. They are specifically implicated in the development of tumors and have both oncogenic and anti-apoptotic effects. Neurotensin receptor 2 (NTSR2), like NTSR1, belongs to the G protein-coupled receptor family and has been linked to analgesia, mental disorders, and hematological cancers. However, several research reports have revealed that it exists in numerous different systems. As a result, it seems to be an extremely promising therapeutic target for a variety of diseases. As NTSR2 is particularly prevalent in the brain and has different distribution and developmental characteristics from NTSR1, it may play a specific role in the nervous system. The present review summarizes the expression and function of NTSR2 in different systems, to highlight its potential as a diagnostic tool or therapeutic target.

Robust Commonsense Reasoning Against Noisy Labels Using Adaptive Correction.

Commonsense reasoning based on knowledge graphs (KGs) is a challenging task that requires predicting complex questions over the described textual contexts and relevant knowledge about the world. However, current methods typically assume clean training scenarios with accurately labeled samples, which are often unrealistic. The training set can include mislabeled samples, and the robustness to label noises is essential for commonsense reasoning methods to be practical, but this problem remains largely unexplored. This work focuses on commonsense reasoning with mislabeled training samples and makes several technical contributions: 1) we first construct diverse augmentations from knowledge and model, and offer a simple yet effective multiple-choice alignment method to divide the training samples into clean, semi-clean, and unclean parts; 2) we design adaptive label correction methods for the semi-clean and unclean samples to exploit the supervised potential of noisy information; and 3) finally, we extensively test these methods on noisy versions of commonsense reasoning benchmarks (CommonsenseQA and OpenbookQA). Experimental results show that the proposed method can significantly enhance robustness and improve overall performance. Furthermore, the proposed method is generally applicable to multiple existing commonsense reasoning frameworks to boost their robustness. The code is available at https://github.com/xdxuyang/CR_Noisy_Labels.

Conjugated Phosphonic Acids Enable Robust Hole Transport Layers for Efficient and Intrinsically Stable Perovskite Solar Cells.

High efficiency and long-term stability are the prerequisites for the commercialization of perovskite solar cells (PSCs). However, inadequate and non-uniform doping of hole transport layers (HTLs) still limits the efficiency improvements, while the intrinsic instability of HTLs caused by ion migration and accumulation is difficult to be addressed by external encapsulation. Here it is shown that the addition of a conjugated phosphonic acid (CPA) to the Spiro-OMeTAD benchmark HTL can greatly enhance the device efficiency and intrinsic stability. Featuring an optimal diprotic-acid structure, indolo(3,2-b)carbazole-5,11-diylbis(butane-4,1-diyl) bis(phosphonic acid) (BCZ) is developed to promote morphological uniformity and mitigate ion migration across both perovskite/HTL and HTL/Ag interfaces, leading to superior charge conductivity, reinforced ion immobilization, and remarkable film stability. The dramatically improved interfacial charge collection endows BCZ-based n-i-p PSCs with a champion power conversion efficiency of 24.51%. More encouragingly, the BCZ-based devices demonstrate remarkable stability under harsh environmental conditions by retaining 90% of initial efficiency after 3000 h in air storage. This work paves the way for further developing robust organic HTLs for optoelectronic devices.

Larger aggregate formed by self-assembly process of the mixture surfactants enhance the dissolution and oxidative removal of non-aqueous phase liquid contaminants in aquifer.

Surfactants can transfer non-aqueous phase liquid (NAPL) contaminants to the aqueous phase, and enhance the removal of the latter in groundwater. However, the extensive use of surfactants causes secondary contamination and increases the non-target consumption of oxidants. It is pressing to develop a surfactant with high phase transfer efficiency and sound compatibility with oxidants to minimize the use of surfactants for groundwater remediation. The phase transfer capability of different surfactants and their binary mixtures, their enhanced KMnO4 oxidation performance for NAPL contaminants as well as influencing factors were investigated to solve the above-mentioned question. The results showed that Tween20, SDBS and BS-12 perform best in terms of phase transfer capability among nonionic, anionic and amphoteric surfactants respectively, and only SDBS and BS-12 produce a synergistic effect among the binary mixtures. The CMC of SDBS/BS-12 was lower than its ideal CMC value, and the self-assembly process of SDBS/BS-12 also formed larger aggregates, which improved the phase transfer performance. Compared to other single surfactants, the removal efficiency of petroleum hydrocarbons in the aquifer sediments was raised by 7.4-33.8 % using the mixed surfactant. The SDBS/BS-12 mixture was compatible with KMnO4 and boosted the reaction of NAPL contaminants with KMnO4 by transferring from the NAPL phase to the aqueous phase. As a result, the NAPL toluene and phenanthrene removal efficiency increased from 37 % and 29 % to 80 % and 86 % respectively. Natural organic matters inhibited the phase transfer efficiency of the SDBS/BS-12 mixture, whereas anions and monovalent cations enhanced the phase transfer capability of the mixture. High-valent cations led to precipitation in the SDBS/BS-12, which could be eliminated by adding Na2Si2O5. The SDBS/BS-12 mixture delivered the same phase transfer efficiency with the dosage of 1.73-23.07 % of other single surfactants, and its cost was equivalent to 0.25-41.7 % of the latter, thus embracing bright application prospects.

The optimal puncture time point of prolonged occlusion flow-mediated dilatation in radial artery catheterization: a prospective observational study.

Previous studies have demonstrated prolonged occlusion flow-mediated dilatation (PO-FMD) could reduce cannulation failure rates and decrease radial artery pulsation loss during trans-radial coronary angiography. However, the time and degree of radial artery dilatation induced after PO-FMD were unclear. This study aimed to evaluate the degree and duration of the radial artery dilation after PO-FMD, and the time point at which the radial artery diameter is expanded to the maximum. This was a prospective observational study. According to the Chinese guideline on the primary prevention of cardiovascular diseases, 142 patients awaking from general anesthesia were divided into two groups: low-risk (LR) group and high-risk (HR) group. Firstly, the baseline radial artery diameter was measured on the left wrist using ultrasound in both groups. Subsequently, the radial artery diameters were obtained continuously at the same location for 5 min after PO-FMD. The baseline radial artery diameter, the maximum radial artery diameter, and the duration of radial artery dilation in the two groups were recorded. The time point at which the radial artery diameter is expanded to the maximum in the LR group and HR group was 26.49 ± 11.69 s and 46.27 ± 12.03 s, respectively (P < 0.01). The time of radial artery dilation and the percentage changes in arterial diameter in HR group were significantly lower than LR group (duration time: mean [mean ± standard]: 136.65 ± 31.55 s vs. 168.98 ± 33.27 s; percentage changes: median [interquartile range] 10.5 [8.6, 12.9] % vs. 15.2 [12.4, 19.0] %). In this study, the optimal puncture time point of PO-FMD in the LR group was 26 s, and in the HR group was 46 s. It would be helpful to guide the time point in radial artery catheterization after PO-FMD.Chinese Clinical Trial Registry identifier: ChiCTR2200066214.

Blood-based biomarkers: diagnostic value in brain tumors (focus on gliomas).

Background: Brain tumors, especially gliomas, are known for high lethality. It is currently understood that the correlations of tumors with coagulation and inflammation have been gradually revealed. Objective: This study aimed to explore the potential value of several reported peripheral blood parameters as comprehensively as possible, with preoperative diagnosis and identification of brain tumors (focus on gliomas). Methods: Patients with central nervous system tumors (craniopharyngioma, ependymoma, spinal meningioma, acoustic neuroma, brain metastases, meningioma, and glioma) or primary trigeminal neuralgia admitted to our hospital were retrospectively analyzed. The results of the routine coagulation factor test, serum albumin test, and blood cell test in peripheral blood were recorded for each group of patients on admission. Neutrophil-lymphocyte ratio (NLR), derived NLR (dNLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), prognostic nutritional index (PNI), the systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), and their pairings were calculated. Their ability to identify brain tumors and their correlation with glioma grade were analyzed. Results: A total of 698 patients were included in this retrospective case-control study. Glioma patients had higher NLR, SII, and PIV but lower LMR. The NLR in the brain metastasis group was lower than that in the control, meningioma, and acoustic neuroma groups, but the SII and PIV were higher than those in the ependymoma group. Fibrinogen, white blood cell count, neutrophil count, NLR, SII, and PIV in the GBM group were higher than those in the control group. In all comparisons, NLR and NLR + dNLR showed the greatest accuracy, with areas under the curve (AUCs) of 0.7490 (0.6482-0.8498) and 0.7481 (0.6457-0.8505), respectively. PIV, dNLR + PIV, and LMR + PIV ranked second, with AUCs of 0.7200 (0.6551-0.7849), 0.7200 (0.6526-0.7874), 0.7204 (0.6530-0.7878) and 0.7206 (0.6536-0.7875), respectively. Conclusion: NLR, PIV, and their combinations show high sensitivity and specificity in the diagnosis of brain tumors, especially gliomas. Overall, our results provide evidence for these convenient and reliable peripheral blood markers.