Mucoadhesive phenylboronic acid-grafted carboxymethyl cellulose hydrogels containing glutathione for treatment of corneal epithelial cells exposed to benzalkonium chloride.

Benzalkonium chloride (BAK) is the most commonly-used preservative in topical ophthalmic medications that may cause ocular surface inflammation associated with oxidative stress and dry eye syndrome. Glutathione (GSH) is an antioxidant in human tears and able to decrease the proinflammatory cytokine release from cells and reactive oxygen species (ROS) formation. Carboxymethyl cellulose (CMC), a hydrophilic polymer, is one of most commonly used artificial tears and can promote the corneal epithelial cell adhesion, migration and re-epithelialization. However, most of commercial artificial tears provide only temporary relief of irritation symptoms and show the short-term treatment effects. In the study, 3-aminophenylboronic acid was grafted to CMC for increase of mucoadhesive properties that might increase the precorneal retention time and maintain the effective therapeutic concentration on the ocular surface. CMC was modified with different degree of substitution (DS) and characterized by Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. Phenylboronic acid (PBA)-grafted CMC hydrogels have interconnected porous structure and shear thinning behavior. Modification of CMC with high DS (H-PBA-CMC) shows the strong bioadhesive force. The optimal concentration of GSH to treat corneal epithelial cells (CECs) was evaluated by cell viability assay. H-PBA-CMC hydrogels could sustained release GSH and decrease the ROS level. H-PBA-CMC hydrogels containing GSH shows the therapeutic effects in BAK-damaged CECs via improvement of inflammation, apoptosis and cell viability. After topical administration of developed hydrogels, there was no ocular irritation in rabbits. These results suggested that PBA-grafted CMC hydrogels containing GSH might have potential applications for treatment of dry eye disease.

An Evolving Landscape: Return of Breast Sensation After Mastectomy Varies by Anatomic Region and Reconstructive Method.

PURPOSE: Loss of breast sensation after mastectomy has been well documented. Postoperative reinnervation of the breast is influenced by factors including reconstructive technique, patient comorbidities, and adjuvant treatment. However, little attention has been paid to the differences in sensation across regions of the breast and the impact of reconstructive method on these regional differences over time. METHODS: Patients undergoing nipple-sparing mastectomy with immediate autologous or alloplastic reconstruction were prospectively followed. Neurosensory testing was performed in 9 breast regions using a pressure-specified sensory device. Patients were stratified by reconstructive technique, and regional sensation was compared at different preoperative and postoperative time points using Student t tests. RESULTS: One hundred ninety-two patients were included; 106 underwent autologous reconstruction via neurotized deep inferior epigastric artery perforator flap, and 86 underwent 2-stage alloplastic reconstruction. Preoperative sensation thresholds did not differ between reconstructive cohorts in any region and averaged 18.1 g/mm2. In the first year after mastectomy, decreased sensation was most pronounced in the inner breast regions and at the nipple areolar complex (NAC) in both reconstructive cohorts. At 4 years postoperatively, sensation increased the most at the NAC in the alloplastic cohort (34.0 g/mm2 decrease) and at the outer lateral region in the autologous cohort (30.4 g/mm2 threshold decrease). The autologous cohort experienced improved sensation compared with the alloplastic cohort in 5 of 9 regions at 1 year postoperatively, and in 7 of 9 regions at 4 years postoperatively; notably, only sensation at the outer superior and outer medial regions did not differ significantly between cohorts at 4 years postoperatively. CONCLUSIONS: Although patients undergoing breast reconstruction experience increased breast sensation over time, the return of sensation is influenced by type of reconstruction and anatomic region. Regions closer to and at the NAC experience the greatest loss of sensation after mastectomy, although the NAC itself undergoes the most sensation recovery of any breast region in those with alloplastic reconstruction.Autologous reconstruction via a neurotized deep inferior epigastric artery perforator flap results in increased return of sensation compared with alloplastic reconstruction, particularly in the inferior and lateral quadrants of the breast.

Impact of Comorbidities on Sensory Return After Breast Reconstruction.

PURPOSE: Breast anesthesia after mastectomy and reconstruction has been an ongoing concern with few improvements made in recent years. At present, there is a lack of studies evaluating the impact of comorbidities on sensation restoration. Identifying risk factors (RF) will be helpful with preoperative counseling. METHODS: This was a prospective study on patients who underwent mastectomy and immediate implant-based or neurotized deep inferior epigastric perforator (DIEP) flap-based reconstruction. Neurosensory testing was performed at predefined time points using a pressure specified device. Patients were stratified based on reconstruction type and comorbidities, including obesity (≥30 kg/m2), age (>55 years), hypertension, alcohol use, and smoking status. Sensory comparisons among the comorbidity groups were conducted using unpaired 2-sample t tests. RESULTS: A total of 239 patients were included in this study with 109 patients in the implant cohort and 131 patients in the DIEP cohort. One patient underwent bilateral reconstruction using both reconstructive modalities. Preoperatively, age older than 55 years was identified as an RF for reduced breast sensation in the implant cohort (difference in threshold, 10.7 g/mm2), whereas obesity was identified as an RF in the DIEP cohort (difference in threshold, 8 g/mm2). During the first 2 years postreconstruction, age older than 55 years and tobacco use history were found to be negatively correlated with breast sensation for both cohorts. With DIEP reconstruction specifically, obesity was identified as an additional RF during the early postoperative period. Of note, none of the comorbidities were found to be long-term RFs for reduced breast sensitivity. All breast sensation levels returned to comparable levels across all comorbidities by 4 years postreconstruction. CONCLUSIONS: Currently, various comorbidities have been recognized as RFs for several postoperative complications including extended postoperative stay, necrosis, infection, and reoperation. However, our findings suggest that, although age, smoking history, and obesity showed transient associations with reduced breast sensation during the initial years postreconstruction, they play no role in the long-term potential of sensory nerve regeneration.

Minimizing Voltage Losses via Synergistically Reducing Hetero-Interface Energy Offset for High Efficiency Perovskite Solar Cells.

The open circuit voltage (VOC) losses at multiple interfaces within perovskite solar cells (PSCs) limit the improvements in power conversion efficiency (PCE). Herein, a tailored strategy is proposed to reduce the energy offset at both hetero-interfaces within PSCs to decrease the VOC losses. For the interface of perovskite and electron transport layer where exists a mass of defects, it uses the pyromellitic acid to serve as a molecular bridge, which reduces non-radiative recombination and energy level offset. For the interface of perovskite and hole transport layer, which includes a passivator of PEAI, the detrimental effect (negative shift of work function) of PEAI passivation and optimizing the interface energy level alignment are neutralized by incorporating (2-(4-(bis(4-methoxyphenyl)amino)phenyl)-1-cyanovinyl)phosphonic acid. Owing to synergistically reduced hetero-interface energy offset, the PSCs achieve a PCE of 25.13%, and the VOC is increased from 1.134 to 1.174 V. In addition, the resulting PSCs possess enhanced stability, the unencapsulated PSCs can maintain ≈96% and ≈97% of their initial PCE after 2000 h of aging under ambient conditions and 210 h under operation conditions.

Northeast Pacific warm blobs sustained via extratropical atmospheric teleconnections.

Large-scale marine heatwaves in the Northeast Pacific (NEP), identified here and previously as 'warm blobs', have devastating impacts on regional ecosystems. An anomalous atmospheric ridge over the NEP is known to be crucial for maintaining these warm blobs, also causing abnormally cold temperatures over North America during the cold season. Previous studies linked this ridge to teleconnections from tropical sea surface temperature anomalies. However, it was unclear whether teleconnections from the extratropics could also contribute to the ridge. Here we show that planetary wave trains, triggered by increased rainfall and latent heat release over the Mediterranean Sea accompanied by decreased rainfall over the North Atlantic, can transport wave energy to the NEP, guided by the westerly jet, and induce a quasi-barotropic ridge there. Our findings provide insights into extratropical teleconnections sustaining the NEP ridge, offering a source of potential predictability for the warm blobs and temperature fluctuations over North America.

Ultrafast photoinduced C-H bond formation from two small inorganic molecules.

The formation of carbon-hydrogen (C-H) bonds via the reaction of small inorganic molecules is of great significance for understanding the fundamental transition from inorganic to organic matter, and thus the origin of life. Yet, the detailed mechanism of the C-H bond formation, particularly the time scale and molecular-level control of the dynamics, remain elusive. Here, we investigate the light-induced bimolecular reaction starting from a van der Waals molecular dimer composed of two small inorganic molecules, H2 and CO. Employing reaction microscopy driven by a tailored two-color light field, we identify the pathways leading to C-H photobonding thereby producing HCO+ ions, and achieve coherent control over the reaction dynamics. Using a femtosecond pump-probe scheme, we capture the ultrafast formation time, i.e., 198 ± 16 femtoseconds. The real-time visualization and coherent control of the dynamics contribute to a deeper understanding of the most fundamental bimolecular reactions responsible for C-H bond formation, thus contributing to elucidate the emergence of organic components in the universe.

Identification of a de novo CACNA1B variant and a start-loss ADRA2B variant in paroxysmal kinesigenic dyskinesia.

Paroxysmal kinesigenic dyskinesia (PKD) represents the most prevalent form of paroxysmal dyskinesia, characterized by recurrent and transient attacks of involuntary movements triggered by a sudden voluntary action. In this study, whole-exome sequencing was conducted on a cohort of Chinese patients to identify causal mutations. In one young female case, a de novo CACNA1B variant (NM_000718.3:exon3:c.479C > T:p.S160F) was identified as the causative lesion. This finding may broaden the phenotypic spectrum of CACNA1B mutations and provide a prospective cause of primary PKD. Additionally, a novel start-loss variant (NM_000682.7:c.3G > A) within ADRA2B further denied its association with benign adult familial myoclonic epilepsy, and a KCNQ2 E515D variant that was reported as a genetic susceptibility factor for seizures had no damaging effect in this family. In sum, this study established a correlation between CACNA1B and primary PKD, and found valid evidence that further negates the pathogenic role of ADRA2B in benign adult familial myoclonic epilepsy.

Transcriptional patterns of human retinal pigment epithelial cells under protracted high glucose.

BACKGROUND: The retinal pigment epithelium (RPE) is essential for retinal homeostasis. Comprehensively exploring the transcriptional patterns of diabetic human RPE promotes the understanding of diabetic retinopathy (DR). METHODS AND RESULTS: A total of 4125 differentially expressed genes (DEGs) were screened out from the human primary RPE cells subjected to prolonged high glucose (HG). The subsequent bioinformatics analysis is divided into 3 steps. In Step 1, 21 genes were revealed by intersecting the enriched genes from the KEGG, WIKI, and Reactome databases. In Step 2, WGCNA was applied and intersected with the DEGs. Further intersection based on the enrichments with the GO biological processes, GO cellular components, and GO molecular functions databases screened out 12 candidate genes. In Step 3, 13 genes were found to be simultaneously up-regulated in the DEGs and a GEO dataset involving human diabetic retinal tissues. VEGFA and ERN1 were the 2 starred genes finally screened out by overlapping the 3 Steps. CONCLUSION: In this study, multiple genes were identified as crucial in the pathological process of RPE under protracted HG, providing potential candidates for future researches on DR. The current study highlights the importance of RPE in DR pathogenesis.

Actual and Virtual Parks Benefit Quality of Life and Physical Activity: A Cluster Trial.

Urban parks provide connectedness to nature as a health resilience environment for promoting health. Virtual reality can provide opportunities for urban citizens to be exposed to natural elements with health benefits. The purpose was to explore the effects of actual and virtual parks on the quality of life and physical activity of urban residents. The study design was a cluster trial. Participants were healthy adults aged 20-50 years, recruited from three college campuses, and randomly assigned to two experimental groups (n = 30, 32) and one control group (n = 30). The intervention with virtual or actual parks was conducted for 30 min a session once a week for 12 weeks. Outcomes were measured using self-reported questionnaires, including the World Health Organization Quality-of-Life Scale-BREF and International Physical Activity Questionnaire-Short Form. In total, 84 participants completed the interventions and post-intervention measures. Results showed that participants who experienced actual parks had significant increases in the social quality of life and light-intensity physical activity and had decreased body weight. Participants who experienced the virtual parks experienced a significant increase in their mental quality of life. Participants in the experimental groups of both kinds of parks had significant improvements in their self-rated health, physical and environmental quality of life, and sedentary time after the intervention. Urban parks are an important natural resource for citizens' health and physical activity promotion. Virtual parks can simulate actual parks and have similar health benefits and are thus are recommended for citizens who lack opportunities and motivation to go to actual parks.

Physical Regimes and Mechanisms of Picosecond Laser Fragmentation of Gold Nanoparticles in Water from X-ray Probing and Atomistic Simulations.

Laser fragmentation in liquids has emerged as a promising green chemistry technique for changing the size, shape, structure, and phase composition of colloidal nanoparticles, thus tuning their properties to the needs of practical applications. The advancement of this technique requires a solid understanding of the mechanisms of laser-nanoparticle interactions that lead to the fragmentation. While theoretical studies have made impressive practical and mechanistic predictions, their experimental validation is required. Hence, using the picosecond laser fragmentation of Au nanoparticles in water as a model system, the transient melting and fragmentation processes are investigated with a combination of time-resolved X-ray probing and atomistic simulations. The direct comparison of the diffraction profiles predicted in the simulations and measured in experiments has revealed a sequence of several nonequilibrium processes triggered by the laser irradiation. At low laser fluences, in the regime of nanoparticle melting and resolidification, the results provide evidence of a transient superheating of crystalline nanoparticles above the melting temperature. At fluences about three times the melting threshold, the fragmentation starts with evaporation of Au atoms and their condensation into small satellite nanoparticles. As fluence increases above five times the melting threshold, a transition to a rapid (explosive) phase decomposition of superheated nanoparticles into small liquid droplets and vapor phase atoms is observed. The transition to the phase explosion fragmentation regime is signified by prominent changes in the small-angle X-ray scattering profiles measured in experiments and calculated in simulations. The good match between the experimental and computational diffraction profiles gives credence to the physical picture of the cascade of thermal fragmentation regimes revealed in the simulations and demonstrates the high promise of the joint tightly integrated computational and experimental efforts.

Integrated metabolomic and transcriptomic analyses provide insights into regulation mechanisms during bulbous stem development in the Chinese medicinal herb plant, Stephania kwangsiensis.

BACKGROUND: Stephania kwangsiensis Lo (Menispermaceae) is a well-known Chinese herbal medicine, and its bulbous stems are used medicinally. The storage stem of S. kwangsiensis originated from the hypocotyls. To date, there are no reports on the growth and development of S. kwangsiensis storage stems. RESULTS: The bulbous stem of S. kwangsiensis, the starch diameter was larger at the stable expanding stage (S3T) than at the unexpanded stage (S1T) or the rapidly expanding stage (S2T) at the three different time points. We used ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and Illumina sequencing to identify key genes involved in bulbous stem development. A large number of differentially accumulated metabolites (DAMs) and differentially expressed genes (DEGs) were identified. Based on the differential expression profiles of the metabolites, alkaloids, lipids, and phenolic acids were the top three differentially expressed classes. Compared with S2T, significant changes in plant signal transduction and isoquinoline alkaloid biosynthesis pathways occurred at both the transcriptional and metabolic levels in S1T. In S2T compared with S3T, several metabolites involved in tyrosine metabolism were decreased. Temporal analysis of S1T to S3T indicated the downregulation of phenylpropanoid biosynthesis, including lignin biosynthesis. The annotation of key pathways showed an up-down trend for genes and metabolites involved in isoquinoline alkaloid biosynthesis, whereas phenylpropanoid biosynthesis was not completely consistent. CONCLUSIONS: Downregulation of the phenylpropanoid biosynthesis pathway may be the result of carbon flow into alkaloid synthesis and storage of lipids and starch during the development of S. kwangsiensis bulbous stems. A decrease in the number of metabolites involved in tyrosine metabolism may also lead to a decrease in the upstream substrates of phenylpropane biosynthesis. Downregulation of lignin synthesis during phenylpropanoid biosynthesis may loosen restrictions on bulbous stem expansion. This study provides the first comprehensive analysis of the metabolome and transcriptome profiles of S. kwangsiensis bulbous stems. These data provide guidance for the cultivation, breeding, and harvesting of S. kwangsiensis.

Maillard reaction intermediates in Chinese Baijiu and their effects on Maillard reaction related flavor compounds during aging.

This study investigated the Maillard reaction in Baijiu and the effects of extended aging in the presence of Maillard reaction intermediates (MRIs) on aromatic compounds, particularly focusing on heterocyclic changes. MRIs with different aroma types in Baijiu aged 1-18 years and force-aged for 6 weeks were determined. Results revealed that MRIs in soy sauce aroma-type Baijiu were significantly more abundant than those in other types of Baijiu. Changes in MRIs were observed and compared in aging and forced-aging Baijiu. Additionally, the distribution and variation of heterocycles in Baijiu were examined, which revealed an increase in N-heterocycle levels but a decrease in S- and O-heterocycle levels to a certain extent. The results of this study demonstrate that the Maillard reaction during the aging of Baijiu influences heterocycle concentrations, thereby improving flavor of aged Baijiu. Research into heterocycles and the Maillard reaction may help elucidate the aromatic evolution of Baijiu with aging and provide guidance for Baijiu storage.

Chitinase 3-like 1 expression associated with lymphatic metastasis and prognosis in urothelial carcinoma of the bladder.

Objectives: Lymphatic metastasis, an early stage of the metastasis process, is associated with adverse clinical outcomes in urothelial carcinoma of the bladder (UCB). However, the role of inflammation in triggering lymphatic metastasis remains unclear. Methods: We employed an RNA-sequencing cohort (n = 50) from Sun Yat-Sen Memorial Hospital (SYMH) to identify the most highly upregulated inflammatory gene associated with lymphatic metastasis. Using immunohistochemistry and immunofluorescence analyses, we validated the association of the identified molecule with clinical features and prognosis in an independent UCB cohort (n = 244) from SYMH. We also analysed TCGA-BLCA cohort (n = 408) to identify its potential biological pathways and immune landscape. Results: In our study, chitinase 3-like 1 (CHI3L1) emerged as a significantly overexpressed proinflammatory mediator in UCB tissues with lymphatic metastasis compared to those without lymphatic metastasis (81.1% vs. 47.8%, P < 0.001). Within UCB tissues, CHI3L1 was expressed in both stromal cells (52.8%) and tumor cells (7.3%). Moreover, CHI3L1+ stromal cells, but not tumor cells, exhibited independent prognostic significance for both overall survival (P < 0.001) and recurrence-free survival (P = 0.006). CHI3L1+ stromal cells were positively associated with D2-40+ lymphatic vessel density (P < 0.001) and the immunosuppressive PD-L1/PD-1/CD8 axis in UCB tissues (all P < 0.05). A bioinformatics analysis also identified a positive association between CHI3L1 expression and lymphangiogenesis or immunosuppression pathways. Conclusion: Our study established a clear association between stromal CHI3L1 expression and lymphatic metastasis, suggesting that stromal CHI3L1 expression is a potential prognostic marker for bladder cancer patients.

Effects of different exercise interventions on chemotherapy-related cognitive impairment in patients with breast cancer: a study protocol for systematic review and network meta-analysis.

INTRODUCTION: Breast cancer stands as the most prevalent type of cancer affecting women globally, and chemotherapy plays a pivotal role in its treatment by diminishing tumour recurrence and enhancing the survival rates of patients. However, chemotherapy-related cognitive impairment (CRCI) often occurs in patients undergoing treatment. Although multiple clinical trials have indicated that exercise therapy can improve CRCI in patients with breast cancer, there are variations in the types of exercise interventions and their effectiveness. We aim to perform a pioneering network meta-analysis (NMA) to assess and prioritise the effectiveness of various exercise interventions in enhancing cognitive function in patients with breast cancer undergoing chemotherapy. METHODS AND ANALYSIS: We will search multiple databases, including PubMed, Web of Science, Cochrane, Embase, China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, Wanfang and Sinomed databases, from their inception to May 2023. The main outcome is the cognitive function changes in patients with breast cancer, including subjective and objective results. We will specifically include randomised controlled trials reported in English and Chinese languages, whose primary outcome consists of an assessment of the cognitive function of patients with breast cancer using standardised and validated assessment tools, encompassing both subjective and objective outcomes. The quality of all the trials included will be evaluated based on 'Version 2 of the Cochrane tool for assessing the risk of bias in randomized controlled trials (RoB2)'. We will conduct a Bayesian NMA to thoroughly evaluate and compare the effectiveness of different exercise interventions. We will use cumulative ranking probability plots to estimate the ranking of the best interventions for various exercises. Network plots and funnel plots will be employed to display the study sizes and participants of each exercise intervention, as well as potential publication biases. ETHICS AND DISSEMINATION: The study findings will be shared via peer-reviewed journals to ensure the highest quality and credibility of the research. As the reporting will not include any private patient data, there are no ethical considerations associated with this protocol. PROSPERO REGISTRATION NUMBER: CRD42023406597.

Is 3T MR nerve-bone fusion imaging a viable alternative to MRI-CBCT to identify the relationship between the inferior alveolar nerve and mandibular third molar.

OBJECTIVES: To investigate the feasibility of MRI nerve-bone fusion imaging in assessing the relationship between inferior alveolar nerve (IAN) / mandibular canal (MC) and mandibular third molar (MTM) compared with MRI-CBCT fusion. MATERIALS AND METHODS: The MRI nerve-bone fusion and MRI-CBCT fusion imaging were performed in 20 subjects with 37 MTMs. The Hausdorff distance (HD) value and dice similarity coefficient (DSC) was calculated. The relationship between IAN/MC and MTM roots, inflammatory, and fusion patterns were compared between these two fused images. The reliability was assessed using a weighted κ statistic. RESULTS: The mean HD and DSC ranged from 0.62 ~ 1.35 and 0.83 ~ 0.88 for MRI nerve-bone fusion, 0.98 ~ 1.50 and 0.76 ~ 0.83 for MRI-CBCT fusion. MR nerve-bone fusion had considerable reproducibility compared to MRI-CBCT fusion in relation classification (MR nerve-bone fusion κ = 0.694, MRI-CBCT fusion κ = 0.644), direct contact (MR nerve-bone fusion κ = 0.729, MRI-CBCT fusion κ = 0.720), and moderate to good agreement for inflammation detection (MR nerve-bone fusion κ = 0.603, MRI-CBCT fusion κ = 0.532, average). The MR nerve-bone fusion imaging showed a lower ratio of larger pattern compared to MR-CBCT fusion (16.2% VS 27.3% in the molar region, and 2.7% VS 5.4% in the retromolar region). And the average time spent on MR nerve-bone fusion and MRI-CBCT fusion was 1 min and 3 min, respectively. CONCLUSIONS: Both MR nerve-bone fusion and MRI-CBCT fusion exhibited good consistency in evaluating the spatial relationship between IAN/MC and MTM, fusion effect, and inflammation detection. CLINICAL RELEVANCE: MR nerve-bone fusion imaging can be a preoperative one-stop radiation-free examination for patients at high risk for MTM surgery.

Injury Mortality of Children and Adolescents Aged 0-19 Years - China, 2010-2021.

Introduction: To examine the recent trends in child injury mortality in China. Methods: Injury mortality data of 2010-2021 for children and adolescents aged 0-19 years were from the China Health Statistics Yearbook. Injury mortality disparities across urban vs. rural locations, gender, and age groups were scrutinized. Annual percent change (APC), average annual percent change (AAPC), and their 95% confidence intervals (95% CI) were estiamted usimg Joinpoint regression models. Results: The age-standardized injury mortality significantly dropped from 21.87 to 9.41 per 100,000 population among children and youth aged 0-19 years during 2010-2021, with an AAPC of -6.7% (95% CI: -8.2%, -5.2%). The urban-rural disparity and gender gap in injury mortality reduced gradually. In 2021, drowning and road traffic crashes were the top two causes of child injury deaths, explaing 31.1% and 27.9% of total injury deaths, respectively. Suffocation accounted for 62.3% of injury deaths among infants younger than a year. Alarmingly, the suicide mortality rate rose from 2.16 to 3.42 per 100,000 population between 2010 and 2021 among teenagers aged 15-19 years. Subgroup analyses yielded similar results. Conclusions: During 2010-2021, the injury mortality decreased significantly among Chinese children and adolescents, and the responding urban-rural disparities narrowed.

Spatiotemporal cerebral blood flow dynamics underlies emergence of the limbic-sensorimotor-association cortical gradient in human infancy.

Infant cerebral blood flow (CBF) delivers nutrients and oxygen to fulfill brain energy consumption requirements for the fastest period of postnatal brain development across lifespan. However, organizing principle of whole-brain CBF dynamics during infancy remains obscure. Leveraging a unique cohort of 100+ infants with high-resolution arterial spin labeled MRI, we found the emergence of the cortical hierarchy revealed by highest-resolution infant CBF maps available to date. Infant CBF across cortical regions increased in a biphasic pattern with initial rapid and sequentially slower rate, with break-point ages increasing along the limbic-sensorimotor-association cortical gradient. Increases in CBF in sensorimotor cortices were associated with enhanced language and motor skills, and frontoparietal association cortices for cognitive skills. The study discovered emergence of the hierarchical limbic-sensorimotor-association cortical gradient in infancy, and offers standardized reference of infant brain CBF and insight into the physiological basis of cortical specialization and real-world infant developmental functioning.

Microwave ablation combined with PD-L1 blockade synergistically promotes Cxcl9-mediated antitumor immunity.

Although microwave ablation (MWA) is an important curative therapy in colorectal cancer liver metastasis, recurrence still occurs clinically. Our previous studies have shown that the expression of programmed cell death 1 ligand 1 (PD-L1) is upregulated following MWA, suggesting that MWA combined with anti-PD-L1 treatment can serve as a promising clinical therapeutic strategy against cancer. Using MWA-treated preclinical mice models, MWA combined with αPD-L1 treatment decreased tumor growth and prolonged overall survival (OS). Furthermore, through flow cytometry and single-cell RNA sequencing analysis, we determined that the MWA plus αPD-L1 therapy significantly suppressed CD8+ T cell exhaustion and enhanced their effector function. A significant increase in γ-interferon (IFN-γ) stimulated transcription factors, specifically Irf8, was observed. This enhancement facilitated the polarization of tumor-associated macrophages (TAM1s and TAM2s) through the nuclear factor-κB/JAK-STAT1 signaling pathway. Furthermore, the combination therapy stimulated the production of CXC motif chemokine ligand (CXCL9) by TAM1s and tumor cells, potentially increasing the chemotaxis of CD8 T cells and Th1 cells. Knocking out Cxcl9 in MC38 tumor cells or using CXCL9 blockade enhanced tumor growth of untreated tumors and shortened OS. Taken together, our study showed that blocking the IFN-γ-Cxcl9-CD8+ T axis promoted tumor progression and discovered a potential involvement of IRF8-regulated TAMs in preventing T cell exhaustion. Collectively, we identified that the combination of MWA with anti-PD-L1 treatment holds promise as a therapeutic strategy to rejuvenate the immune response against tumors. This merits further exploration in clinical studies.

Multilevel Information Encryption Based on Thermochromic Perovskite Microcapsules via Orthogonal Photic and Thermal Stimuli Responses.

Increasing modal variations of stimulus-responsive materials ensure the high capacity and confidentiality of information storage and encryption systems that are crucial to information security. Herein, thermochromic perovskite microcapsules (TPMs) with dual-variable and quadruple-modal reversible properties are designed and prepared on the original oil-in-fluorine (O/F) emulsion system. The TPMs respond to the orthogonal variations of external UV and thermal stimuli in four reversible switchable modes and exhibit excellent thermal, air, and water stability due to the protection of perovskites by the core-shell structure. Benefiting from the high-density information storage TPMs, multiple information encryptions and decryptions are demonstrated. Moreover, a set of devices are assembled for a multilevel information encryption system. By taking advantage of TPMs as a "private key" for decryption, the signal can be identified as the corresponding binary ASCII code and converted to the real message. The results demonstrate a breakthrough in high-density information storage materials as well as a multilevel information encryption system based on switchable quadruple-modal TPMs.

Bergaptol inhibits glioma cell proliferation and induces apoptosis via STAT3/Bcl-2 pathway.

Glioblastoma (GBM) is the most common primary malignant brain tumour and lacks therapeutic options with significant effects. The aberrant activation of STAT3 is a critical factor in glioma progression via activating multiple signalling pathways that promote glioma. Among them, the antiapoptotic gene Bcl-2 could be upregulated by p-STAT3, which is an important reason for the continuous proliferation of glioma. We previously reported that bergaptol, a natural furanocoumarin widely found in citrus products, exerts antineuroinflammatory effects by inhibiting the overactivation of STAT3. Here, we aimed to evaluate whether bergaptol could promote glioma apoptosis by inhibiting the STAT3/Bcl-2 pathway. This study found that bergaptol inhibited the proliferation and migration of GBM cell lines (U87 and A172) and promoted apoptosis in vitro. We also found that bergaptol significantly inhibited the STAT3/Bcl-2 pathway in GBM cells. U87 cells were implanted intracranially into nude mice to establish a glioma model, and glioma-bearing mice were treated with bergaptol (40 mg/kg). Bergaptol treatment significantly inhibited glioma growth and prolonged the glioma-bearing mice's survival time. In addition, bergaptol administration also significantly inhibited the STAT3/Bcl-2 pathway of tumour tissue in vivo. Overall, we found that bergaptol could effectively play an antiglioma role by inhibiting STAT3/Bcl-2 pathway, suggesting the potential efficacy of bergaptol in treating glioma.