A brain-to-gut signal controls intestinal fat absorption.

Although fat is a crucial source of energy in diets, excessive intake leads to obesity. Fat absorption in the gut is prevailingly thought to occur organ-autonomously by diffusion1-3. Whether the process is controlled by the brain-to-gut axis, however, remains largely unknown. Here we demonstrate that the dorsal motor nucleus of vagus (DMV) plays a key part in this process. Inactivation of DMV neurons reduces intestinal fat absorption and consequently causes weight loss, whereas activation of the DMV increases fat absorption and weight gain. Notably, the inactivation of a subpopulation of DMV neurons that project to the jejunum shortens the length of microvilli, thereby reducing fat absorption. Moreover, we identify a natural compound, puerarin, that mimics the suppression of the DMV-vagus pathway, which in turn leads to reduced fat absorption. Photoaffinity chemical methods and cryogenic electron microscopy of the structure of a GABAA receptor-puerarin complex reveal that puerarin binds to an allosteric modulatory site. Notably, conditional Gabra1 knockout in the DMV largely abolishes puerarin-induced intestinal fat loss. In summary, we discover that suppression of the DMV-vagus-jejunum axis controls intestinal fat absorption by shortening the length of microvilli and illustrate the therapeutic potential of puerarin binding to GABRA1 in fat loss.

Learning-dependent gating of hippocampal inputs by frontal interneurons.

The hippocampus is a brain region that is essential for the initial encoding of episodic memories. However, the consolidation of these memories is thought to occur in the neocortex, under guidance of the hippocampus, over the course of days and weeks. Communication between the hippocampus and the neocortex during hippocampal sharp wave-ripple oscillations is believed to be critical for this memory consolidation process. Yet, the synaptic and circuit basis of this communication between brain areas is largely unclear. To address this problem, we perform in vivo whole-cell patch-clamp recordings in the frontal neocortex and local field potential recordings in CA1 of head-fixed mice exposed to a virtual-reality environment. In mice trained in a goal-directed spatial task, we observe a depolarization in frontal principal neurons during hippocampal ripple oscillations. Both this ripple-associated depolarization and goal-directed task performance can be disrupted by chemogenetic inactivation of somatostatin-positive (SOM+) interneurons. In untrained mice, a ripple-associated depolarization is not observed, but it emerges when frontal parvalbumin-positive (PV+) interneurons are inactivated. These results support a model where SOM+ interneurons inhibit PV+ interneurons during hippocampal activity, thereby acting as a disinhibitory gate for hippocampal inputs to neocortical principal neurons during learning.

Iridium(III) carbene complexes as potent girdin inhibitors against metastatic cancers.

Many cancer-driving protein targets remain undruggable due to a lack of binding molecular scaffolds. In this regard, octahedral metal complexes with unique and versatile three-dimensional structures have rarely been explored as inhibitors of undruggable protein targets. Here, we describe antitumor iridium(III) pyridinium-N-heterocyclic carbene complex 1a, which profoundly reduces the viability of lung and breast cancer cells as well as cancer patient-derived organoids at low micromolar concentrations. Compound 1a effectively inhibits the growth of non-small-cell lung cancer and triple-negative breast cancer xenograft tumors, impedes the metastatic spread of breast cancer cells, and can be modified into an antibody-drug conjugate payload to achieve precise tumor delivery in mice. Identified by thermal proteome profiling, an important molecular target of 1a in cellulo is Girdin, a multifunctional adaptor protein that is overexpressed in cancer cells and unequivocally serves as a signaling hub for multiple pivotal oncogenic pathways. However, specific small-molecule inhibitors of Girdin have not yet been developed. Notably, 1a exhibits high binding affinity to Girdin with a Kd of 1.3 µM and targets the Girdin-linked EGFR/AKT/mTOR/STAT3 cancer-driving pathway, inhibiting cancer cell proliferation and metastatic activity. Our study reveals a potent Girdin-targeting anticancer compound and demonstrates that octahedral metal complexes constitute an untapped library of small-molecule inhibitors that can fit into the ligand-binding pockets of key oncoproteins.

Highly pathogenic PRRSV upregulates IL-13 production through nonstructural protein 9-mediated inhibition of N6-methyladenosine demethylase FTO.

Porcine reproductive and respiratory syndrome virus (PRRSV), a highly infectious virus, causes severe losses in the swine industry by regulating the inflammatory response, inducing tissue damage, suppressing the innate immune response, and promoting persistent infection in hosts. Interleukin-13 (IL-13) is a cytokine that plays a critical role in regulating immune responses and inflammation, particularly in immune-related disorders, certain types of cancer, and numerous bacterial and viral infections; however, the underlying mechanisms of IL-13 regulation during PRRSV infection are not well understood. In this study, we demonstrated that PRRSV infection elevates IL-13 levels in porcine alveolar macrophages. PRRSV enhances m6A-methylated RNA levels while reducing the expression of fat mass and obesity associated protein (FTO, an m6A demethylase), thereby augmenting IL-13 production. PRRSV nonstructural protein 9 (nsp9) was a key factor for this modulation. Furthermore, we found that the residues Asp567, Tyr586, Leu593, and Asp595 were essential for nsp9 to induce IL-13 production via attenuation of FTO expression. These insights delineate PRRSV nsp9's role in FTO-mediated IL-13 release, advancing our understanding of PRRSV's impact on host immune and inflammatory responses.

Missense mutation in the activation segment of the kinase CK2 models Okur-Chung neurodevelopmental disorder and alters the hippocampal glutamatergic synapse.

Exome sequencing has enabled the identification of causative genes of monogenic forms of autism, amongst them, in 2016, CSNK2A1, the gene encoding the catalytic subunit of the kinase CK2, linking this kinase to Okur-Chung Neurodevelopmental Syndrome (OCNDS), a newly described neurodevelopmental condition with many symptoms resembling those of autism spectrum disorder. Thus far, no preclinical model of this condition exists. Here we describe a knock-in mouse model that harbors the K198R mutation in the activation segment of the α subunit of CK2. This region is a mutational hotspot, representing one-third of patients. These mice exhibit behavioral phenotypes that mirror patient symptoms. Homozygous knock-in mice die mid-gestation while heterozygous knock-in mice are born at half of the expected mendelian ratio and are smaller in weight and size than wildtype littermates. Heterozygous knock-in mice showed alterations in cognition and memory-assessing paradigms, enhanced stereotypies, altered circadian activity patterns, and nesting behavior. Phosphoproteome analysis from brain tissue revealed alterations in the phosphorylation status of major pre- and postsynaptic proteins of heterozygous knock-in mice. In congruence, we detect reduced synaptic maturation in hippocampal neurons and attenuated long-term potentiation in the hippocampus of knock-in mice. Taken together, heterozygous knock-in mice (CK2αK198R/+) exhibit significant face validity, presenting ASD-relevant phenotypes, synaptic deficits, and alterations in synaptic plasticity, all of which strongly validate this line as a mouse model of OCNDS.

ALKBH5 regulates chicken adipogenesis by mediating LCAT mRNA stability depending on m6A modification.

BACKGROUND: Previous studies have demonstrated the role of N6-methyladenosine (m6A) RNA methylation in various biological processes, our research is the first to elucidate its specific impact on LCAT mRNA stability and adipogenesis in poultry. RESULTS: The 6 100-day-old female chickens were categorized into high (n = 3) and low-fat chickens (n = 3) based on their abdominal fat ratios, and their abdominal fat tissues were processed for MeRIP-seq and RNA-seq. An integrated analysis of MeRIP-seq and RNA-seq omics data revealed 16 differentially expressed genes associated with to differential m6A modifications. Among them, ELOVL fatty acid elongase 2 (ELOVL2), pyruvate dehydrogenase kinase 4 (PDK4), fatty acid binding protein 9 (PMP2), fatty acid binding protein 1 (FABP1), lysosomal associated membrane protein 3 (LAMP3), lecithin-cholesterol acyltransferase (LCAT) and solute carrier family 2 member 1 (SLC2A1) have ever been reported to be associated with adipogenesis. Interestingly, LCAT was down-regulated and expressed along with decreased levels of mRNA methylation methylation in the low-fat group. Mechanistically, the highly expressed ALKBH5 gene regulates LCAT RNA demethylation and affects LCAT mRNA stability. In addition, LCAT inhibits preadipocyte proliferation and promotes preadipocyte differentiation, and plays a key role in adipogenesis. CONCLUSIONS: In conclusion, ALKBH5 mediates RNA stability of LCAT through demethylation and affects chicken adipogenesis. This study provides a theoretical basis for further understanding of RNA methylation regulation in chicken adipogenesis.

Highly Efficient and Scalable p-i-n Perovskite Solar Cells Enabled by Poly-metallocene Interfaces.

Inverted p-i-n perovskite solar cells (PSCs) are easy to process but need improved interface characteristics with reduced energy loss to prevent efficiency drops when increasing the active photovoltaic area. Here, we report a series of poly ferrocenyl molecules that can modulate the perovskite surface enabling the construction of small- and large-area PSCs. We found that the perovskite-ferrocenyl interaction forms a hybrid complex with enhanced surface coordination strength and activated electronic states, leading to lower interfacial nonradiative recombination and charge transport resistance losses. The resulting PSCs achieve an enhanced efficiency of up to 26.08% for small-area devices and 24.51% for large-area devices (1.0208 cm2). Moreover, the large-area PSCs maintain >92% of the initial efficiency after 2000 h of continuous operation at the maximum power point under 1-sun illumination and 65 °C.

Oroxin A alleviates early brain injury after subarachnoid hemorrhage by regulating ferroptosis and neuroinflammation.

BACKGROUND: Subarachnoid hemorrhage (SAH), a severe subtype of stroke, is characterized by notably high mortality and morbidity, largely due to the lack of effective therapeutic options. Although the neuroprotective potential of PPARg and Nrf2 has been recognized, investigative efforts into oroxin A (OA), remain limited in preclinical studies. METHODS: SAH was modeled in vivo through filament perforation in male C57BL/6 mice and in vitro by exposing HT22 cells to hemin to induce neuronal damage. Following the administration of OA, a series of methods were employed to assess neurological behaviors, brain water content, neuronal damage, cell ferroptosis, and the extent of neuroinflammation. RESULTS: The findings indicated that OA treatment markedly improved survival rates, enhanced neurological functions, mitigated neuronal death and brain edema, and attenuated the inflammatory response. These effects of OA were linked to the suppression of microglial activation. Moreover, OA administration was found to diminish ferroptosis in neuronal cells, a critical factor in early brain injury (EBI) following SAH. Further mechanistic investigations uncovered that OA facilitated the translocation of nuclear factor erythroid 2-related factor 2 (Nrf-2) from the cytoplasm to the nucleus, thereby activating the Nrf2/GPX4 pathway. Importantly, OA also upregulated the expression of FSP1, suggesting a significant and parallel protective effect against ferroptosis in EBI following SAH in synergy with GPX4. CONCLUSION: In summary, this research indicated that the PPARg activator OA augmented the neurological results in rodent models and diminished neuronal death. This neuroprotection was achieved primarily by suppressing neuronal ferroptosis. The underlying mechanism was associated with the alleviation of cellular death through the Nrf2/GPX4 and FSP1/CoQ10 pathways.

A multicentre randomized double-blind placebo-controlled phase III study of the efficacy and safety of xeligekimab (GR1501) in patients with moderate-to-severe plaque psoriasis.

BACKGROUND: Xeligekimab (GR1501) is a fully human monoclonal antibody that selectively neutralizes interleukin (IL)-17A and has shown potential efficacy in treating moderate-to-severe psoriasis in preliminary trials. OBJECTIVES: To evaluate the efficacy and safety of xeligekimab in Chinese patients with moderate-to-severe psoriasis. METHODS: A total of 420 Chinese patients were randomized to 200 mg xeligekimab every 2 weeks (n = 281) or placebo (n = 139) for the first 12 weeks, followed by an extension of the treatment schedule to xeligekimab every 4 weeks for a further 40 weeks. Efficacy was assessed by evaluating achievement of Physician Global Assessment (PGA) 0/1 and 75%, 90% and 100% improvement in Psoriasis Area and Severity Index (PASI 75, PASI 90 and PASI 100, respectively). The safety profile was also evaluated. RESULTS: At week 12, PASI 75, PASI 90 and PASI 100 were achieved in 90.7%, 74.4% and 30.2% of patients in the xeligekimab group vs. 8.6%, 1.4% and 0% of patients in the placebo group, respectively. PGA 0/1 was achieved in 74.4% patients in the xeligekimab group and 3.6% of patients in the placebo group. PASI 75 and PGA 0/1 were maintained until week 52. No unexpected adverse events were recorded. CONCLUSIONS: Xeligekimab showed high efficacy and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.

Psoriasis is a skin disease characterized by scaly and raised patches of skin on any part of the body. The condition can be caused by a combination of how a person's immune system works, their genes and their environment. A cytokine is a substance secreted by certain cells of the immune system that have an effect on other cells. One such cytokine, called IL-17A, has been associated with different inflammatory diseases, including psoriasis. We conducted a large trial in Chinese people with moderate-to-severe psoriasis to look at the efficacy (ability to produce the intended result) and safety of a medicine called xeligekimab (known as a 'monoclonal antibody') which works by targeting IL-17A. We randomly assigned 420 Chinese patients to receive 200 mg of xeligekimab every 2 weeks or a 'placebo' (no active medicine) for the first 12 weeks. We extended the treatment schedule of xeligekimab to every 4 weeks for a further 40 weeks. To assess how the medicine worked, we measured people's psoriasis symptoms and severity. To assess how safe the medicine was, we looked at the side-effects (or 'adverse events'). The results of this trial showed that xeligekimab improved people's psoriasis and itching starting at week 4 of receiving treatment, and more than 60% of people achieved improvement or remission by week 6, which was sustained up to week 52. The safety of xeligekimab was similar to another medicine classed as a monoclonal antibody (called secukinumab) and there were no new or unexpected adverse events reported. Overall, our findings suggest that xeligekimab is a safe and effective medicine for the treatment of psoriasis in Chinese people.

Efficacy and safety of vunakizumab in moderate-to-severe chronic plaque psoriasis: A randomized, double-blind, placebo-controlled phase 3 trial.

BACKGROUND: Vunakizumab, a novel anti-interleukin-17A antibody, has shown promising efficacy for moderate-to-severe plaque psoriasis in a phase 2 trial. OBJECTIVE: We conducted a double-blind, randomized phase 3 trial (NCT04839016) to further evaluate vunakizumab in this population. METHODS: Six hundred ninety subjects were randomized (2:1) to receive vunakizumab 240 mg or placebo at weeks 0, 2, 4, and 8. At week 12, subjects on placebo were switched to vunakizumab 240 mg (weeks 12, 14, 16, and every 4 weeks thereafter). The co-primary endpoints were ≥90% improvement from baseline in the Psoriasis Area and Severity Index score (PASI 90) and a static Physicians Global Assessment score of 0/1 (sPGA 0/1) at week 12. RESULTS: At week 12, the vunakizumab group showed higher PASI 90 (76.8% vs 0.9%) and sPGA 0/1 (71.8% vs 0.4%) response rates, as well as higher PASI 75 (93.6% vs 4.0%), PASI 100 (36.6% vs 0.0%), and sPGA 0 (38.2% vs 0.0%) response rates (all two-sided P < .0001 vs placebo). Efficacy was maintained through week 52 with continuous vunakizumab. Possible treatment-related serious adverse events occurred in 0.9% of vunakizumab-treated subjects. LIMITATIONS: Chinese subjects only; no active comparator. CONCLUSION: Vunakizumab demonstrated robust clinical response at week 12 and through week 52, with good tolerability in moderate-to-severe plaque psoriasis.

The efficacy and safety of monoclonal antibody therapies for interstitial cystitis/bladder pain syndrome: A meta-analysis of randomized controlled trials.

OBJECTIVES: This study aimed to assess the efficacy and safety of monoclonal antibody therapies (MATs) for interstitial cystitis/bladder pain syndrome (IC/BPS). METHODS: A systematic search was conducted across databases including PubMed, Embase, clinicalTrial.gov, and the Cochrane Library Central Register of Controlled Trials. Randomized controlled trials (RCTs) comparing MATs versus placebo were included. Primary outcomes comprised the Global Response Assessment (GRA) scale and the O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI). Additional analyses encompassed mean daily frequency of voids, the O'Leary-Sant Interstitial Cystitis Problem Index, pain scores, and complications. Statistical analyses were performed using Review Manager 5.3. RESULTS: Five high-quality RCTs, comprising 263 patients with IC/BPS, were ultimately selected. MATs were generally effective in treating IC/BPS. Patients receiving MATs exhibited a higher satisfaction rate (odds ratio [OR]: 2.7, confidence interval [CI]: 1.31-5.58, p = 0.007) and lower ICSI scores (mean difference [MD]: -1.44, CI: -2.36 to -0.52, p = 0.002). Moreover, MAT recipients experienced reduced pain (MD: -0.53, CI: -0.79 to -0.26, p < 0.0001) and decreased frequency of urination (MD: -1.91, CI: -2.55 to -1.27, p < 0.00001). Importantly, there were no disparities regarding complication incidence in the MAT and control groups. CONCLUSIONS: The current findings indicate that MATs are effective and safe for treating IC/BPS. Nonetheless, future RCTs with larger sample sizes and long-term follow-up are warranted.

Diagnosis and Treatment of Myxoid Liposarcoma.

OPINION STATEMENT: Myxoid liposarcoma (MLS) is a rare subtype of soft tissue sarcoma that distinguishes itself from conventional subtypes through its propensity for extrapulmonary metastasis. The distinctive magnetic resonance imaging (MRI) characteristics of MLS render it an invaluable tool for identifying primary and secondary lesions. Pathologically, MLS is characterized by the FUS-DDIT3 gene fusion. Accurate diagnosis, facilitated by MRI and pathological assessment, is critical for prognostication and the formulation of appropriate treatment strategies. Surgery remains the cornerstone of local management for MLS. The combination of surgery and radiotherapy can significantly reduce the local recurrence rate in MLS, as it is highly sensitive to both radiotherapy and chemotherapy. Additionally, for high-risk MLS cases with a large tumor diameter, chemotherapy has been shown to improve survival. The comprehensive treatment approach for MLS demonstrates superior local recurrence rates and survival rates compared to most soft tissue sarcomas. Current research focuses on developing effective therapies for unresectable or advanced disease based on genomic and phenotypic characteristics as well as the immune-tumor microenvironment.

Efficacy and safety of topical minocycline foam (FMX101 4%) in treatment of Chinese subjects with moderate-to-severe facial acne vulgaris: A phase 3, multi-centre, randomized, double-blind, vehicle-controlled study.

BACKGROUND: FMX101 4%, as a topical foam formulation of minocycline, has been approved by US Food and Drug Administration for the treatment of moderate-to-severe acne vulgaris (AV). OBJECTIVE: To evaluate the efficacy and safety of FMX101 4% in treating Chinese subjects with moderate-to-severe facial AV. METHODS: This was a multi-centre, randomized, double-blind, vehicle-controlled phase 3 study in Chinese subjects with moderate-to-severe AV. Eligible subjects were randomized 2:1 to receive either FMX101 4% or vehicle foam treatment for 12 weeks. The primary efficacy endpoint was the change in inflammation lesion count (ILC) from baseline at week 12. The key secondary endpoint was the treatment success rate according to Investigator's Global Assessment (IGA) at week 12. RESULTS: In total, 372 subjects were randomized into two groups (FMX101 4% group, n = 248; vehicle group, n = 124). After 12 weeks treatment, the reduction in ILC from baseline was statistically significant in favour of FMX101 4%, compared with vehicle foam (-21.0 [0.08] vs. -12.3 [1.14]; LSM [SE] difference, -8.7 [1.34]; 95% CI [-11.3, -6.0]; p < 0.001). FMX101 4% treatment yielded significantly higher IGA treatment success rate at week 12 as compared to the control treatment (8.06% vs. 0%). Applying FMX101 4% also resulted in significant reduction in noninflammatory lesion count (nILC) versus vehicle foam at week 12 (-19.4 [1.03] vs. -14.9 [1.47]; LSM [SE] difference, -4.5 [1.74]; 95% CI [-8.0, -1.1]; p = 0.009). Most treatment-emergent adverse events (TEAEs) were mild-to-moderate in severity, and no treatment-related treatment-emergent serious adverse event (TESAE) occurred. Thus, FMX101 4% was considered to be a safe and well-tolerated product during the 12-week treatment period. CONCLUSION: FMX101 4% treatment for 12 weeks could lead to significantly reduced ILC and nILC, and improved IGA treatment success rate in Chinese subjects with moderate-to-severe facial AV. It also showed a well acceptable safe and tolerability profile.

Human-multimodal deep learning collaboration in 'precise' diagnosis of lupus erythematosus subtypes and similar skin diseases.

BACKGROUND: Lupus erythematosus (LE) is a spectrum of autoimmune diseases. Due to the complexity of cutaneous LE (CLE), clinical skin image-based artificial intelligence is still experiencing difficulties in distinguishing subtypes of LE. OBJECTIVES: We aim to develop a multimodal deep learning system (MMDLS) for human-AI collaboration in diagnosis of LE subtypes. METHODS: This is a multi-centre study based on 25 institutions across China to assist in diagnosis of LE subtypes, other eight similar skin diseases and healthy subjects. In total, 446 cases with 800 clinical skin images, 3786 multicolor-immunohistochemistry (multi-IHC) images and clinical data were collected, and EfficientNet-B3 and ResNet-18 were utilized in this study. RESULTS: In the multi-classification task, the overall performance of MMDLS on 13 skin conditions is much higher than single or dual modals (Sen = 0.8288, Spe = 0.9852, Pre = 0.8518, AUC = 0.9844). Further, the MMDLS-based diagnostic-support help improves the accuracy of dermatologists from 66.88% ± 6.94% to 81.25% ± 4.23% (p = 0.0004). CONCLUSIONS: These results highlight the benefit of human-MMDLS collaborated framework in telemedicine by assisting dermatologists and rheumatologists in the differential diagnosis of LE subtypes and similar skin diseases.

Platinum(II) N-heterocyclic carbene complexes arrest metastatic tumor growth.

Vimentin is a cytoskeletal intermediate filament protein that plays pivotal roles in tumor initiation, progression, and metastasis, and its overexpression in aggressive cancers predicted poor prognosis. Herein described is a highly effective antitumor and antimetastatic metal complex [PtII(C^N^N)(NHC2Bu)]PF6 (Pt1a; HC^N^N = 6-phenyl-2,2'-bipyridine; NHC= N-heterocyclic carbene) that engages vimentin via noncovalent binding interactions with a distinct orthogonal structural scaffold. Pt1a displays vimentin-binding affinity with a dissociation constant of 1.06 µM from surface plasmon resonance measurements and fits into a pocket between the coiled coils of the rod domain of vimentin with multiple hydrophobic interactions. It engages vimentin in cellulo, disrupts vimentin cytoskeleton, reduces vimentin expression in tumors, suppresses xenograft growth and metastasis in different mouse models, and is well tolerated, attributable to biotransformation to less toxic and renal-clearable platinum(II) species. Our studies uncovered the practical therapeutic potential of platinum(II)‒NHC complexes as effective targeted chemotherapy for combating metastatic and cisplatin-resistant cancers.

Four new alkaloids from the roots of Dactylicapnos scandens.

Four new alkaloids (1 - 4), together with five known ones (5 - 9), were isolated from the bulbs of Dactylicapnos scandens. The structures were determined by analysis of their spectroscopic data and quantum-chemical calculations. All the isolates were tested for their ability to modulate neuronal Ca2+ mobilization in primary cultured neocortical neurons. Compound 8 inhibited spontaneous Ca2+ oscillations at low micromolar concentrations.

Mediating role of systemic inflammation in the association between volatile organic compounds exposure and periodontitis: NHANES 2011-2014.

BACKGROUND: Volatile organic compounds (VOCs) are ubiquitous environmental pollutants which have been suggested to have adverse effects on human health. While the influence of environmental pollutant exposures on periodontitis has attracted elevating attention in recent years, the epidemiological evidence on the association between VOCs exposure and periodontitis was scarce. This study aimed to investigate the potential mediating role of systemic inflammation factors in the complex association between VOCs exposure and periodontitis. METHODS: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014, we examined the impacts of VOCs exposure on periodontitis. Concentrations of urinary metabolites of VOCs (mVOCs) were measured using electrospray tandem mass spectrometry to evaluate internal VOCs exposure. Multivariable logistic regression, restricted cubic spline regression (RCS), Bayesian kernel machine regression (BKMR) and Quantile g-computation (QGC) models were performed to investigate the impacts of VOCs exposure on periodontitis. Mediation models were applied to assess the mediated effects of systemic inflammation on the association between mixed VOCs exposure and periodontitis. Besides, we analyzed the association between mixed VOCs exposure and periodontitis in stratified age, gender, and smoking status subgroups. RESULTS: 1,551 participants were ultimately included for further analyses, of whom 45.20% suffering from periodontitis. Multivariable logistic regression and RCS identified positive associations between single urinary mVOCs and periodontitis (P < 0.05). Notably, BKMR and QGC models suggested that mixed VOCs exposure was significantly associated with periodontitis, with 2-Aminothiazoline-4-carboxylic acid (ATCA) contributing the most (conditional posterior inclusion probability = 0.997). Moreover, systemic inflammation markers (leukocyte and lymphocyte counts) were found to partly mediate the association between VOCs exposure and periodontitis (P < 0.05). No interaction effect was identified between mixed VOCs exposure and periodontitis in age, gender and smoking status subgroups (P > 0.05). CONCLUSION: This study demonstrated a positive association between VOCs exposure and periodontitis, which was potentially mediated by systemic inflammation factors. Further longitudinal researches are demanded to clarify the underlying mechanisms.

Design of Ca-type todorokite catalysts with highly active for the selective reduction of NOx by NH3 at low temperatures.

Ca-type todorokite catalysts were designed and prepared by a simple redox method and applied to the selective reduction of NOx by NH3 (NH3-SCR) for the first time. Compared with the Na-type manjiroite prepared by the same method, the todorokite catalysts with different Mn/Ca ratios showed greatly improved catalytic activity for NOx reduction. Among them, Mn8Ca4 catalyst exhibited the best NH3-SCR performance, achieving 90% NOx conversion within temperature range of 70-275°C and having a high sulphur resistance. Compared to the Na-type manjiroite sample, Ca-type todorokite catalysts possessed an increased size of tunnel, resulting in a larger specific surface area. As increased the amounts of Ca doping, the Na content in Ca-type todorokite catalysts significantly decreased, providing larger amounts of Brønsted acid sites for NH3 adsorption to produce NH4+. The NH4+ species were highly active for reaction with NO + O2, playing a determining role in NH3-SCR process at low temperatures. Meanwhile, larger amounts of surface adsorbed oxygen contained over the Ca-doping samples than that over Na-type manjiroite, promoting the oxidation of NO and fast SCR processes. Over the Ca-type todorokite catalysts, furthermore, nitrates produced during the flow of NO + O2, were more active for reaction with NH3 than that over Na-type manjiroite, benefiting the occurrence of NH3-SCR process. This study provides novel insights into the design of NH3-SCR catalysts with high performance.

Enhancing Efficiency and Stability of Inverted Perovskite Solar Cells through Solution-Processed and Structurally Ordered Fullerene.

The electron transporting layer (ETL) used in high performance inverted perovskite solar cells (PSCs) is typically composed of C60, which requires time-consuming and costly thermal evaporation deposition, posing a significant challenge for large-scale production. To address this challenge, herein, we present a novel design of solution-processible electron transporting material (ETM) by grafting a non-fullerene acceptor fragment onto C60. The synthesized BTPC60 exhibits an exceptional solution processability and well-organized molecular stacking pattern, enabling the formation of uniform and structurally ordered film with high electron mobility. When applied as ETL in inverted PSCs, BTPC60 not only exhibits excellent interfacial contact with the perovskite layer, resulting in enhanced electron extraction and transfer efficiency, but also effectively passivates the interfacial defects to suppress non-radiative recombination. Resultant BTPC60-based inverted PSCs deliver an impressive power conversion efficiency (PCE) of 25.3 % and retain almost 90 % of the initial values after aging at 85 °C for 1500 hours in N2. More encouragingly, the solution-processed BTPC60 ETL demonstrates remarkable film thickness tolerance, and enables a high PCE up to 24.8 % with the ETL thickness of 200 nm. Our results highlight BTPC60 as a promising solution-processed fullerene-based ETM, opening an avenue for improving the scalability of efficient and stable inverted PSCs.

[Application of Photoplethysmography Combined with Deep Learning in Postoperative Monitoring of Flaps].

Objective: Photoelectric volumetric tracing (PPG) exhibits high sensitivity and specificity in flap monitoring. Deep learning (DL) is capable of automatically and robustly extracting features from raw data. In this study, we propose combining PPG with 1D convolutional neural networks (1D-CNN) to preliminarily explore the method's ability to distinguish the degree of embolism and to localize the embolic site in skin flap arteries. Methods: Data were collected under normal conditions and various embolic scenarios by creating vascular emboli in a dermatome artery model and a rabbit dermatome model. These datasets were then trained, validated, and tested using 1D-CNN. Results: As the degree of arterial embolization increased, the PPG amplitude upstream of the embolization site progressively increased, while the downstream amplitude progressively decreased, and the gap between the upstream and downstream amplitudes at the embolization site progressively widened. 1D-CNN was evaluated in the skin flap arterial model and rabbit skin flap model, achieving average accuracies of 98.36% and 95.90%, respectively. Conclusion: The combined monitoring approach of DL and PPG can effectively identify the degree of embolism and locate the embolic site within the skin flap artery.