Coronary Artery Wall Contrast Enhancement Imaging Impact on Disease Activity Assessment in IgG4-RD a direct marker of coronary involvement.

BACKGROUND: Coronary artery wall contrast enhancement (CE) has been applied to non-invasive visualization of changes to the coronary artery wall in systemic lupus erythematosus (SLE). This study investigated the feasibility of quantifying CE to detect coronary involvement in IgG4-related disease (IgG4-RD), as well as the influence on disease activity assessment. METHODS: A total of 93 subjects (31 IgG4-RD; 29 SLE; 33 controls) were recruited in the study. Coronary artery wall imaging was performed in a 3.0T MRI scanner. Serological markers and IgG4-RD Responder Index (IgG4-RD-RI) scores were collected for correlation analysis. RESULTS: Coronary wall CE was observed in 29 (94%) IgG4-RD patients and 22 (76%) SLE patients. Contrast-to-noise ratio (CNR) and total CE area were significantly higher in patient groups compared to controls (CNR: 6.1 ± 2.7 [IgG4-RD] v. 4.2 ± 2.3 [SLE] v. 1.9 ± 1.5 [control], P < 0.001; Total CE area: 3.0 [3.0-6.6] v. 1.7 [1.5-2.6] v. 0.3 [0.3-0.9], P < 0.001). In the IgG4-RD group, CNR and total CE area were correlated with the RI (CNR: r =0.55, P =0.002; total CE area: r = 0.39, P = 0.031). RI´ scored considering coronary involvement by CE, differed significantly from RI scored without consideration of CE (RI v. RI´: 15 ± 6v. 16 ± 6, P < 0.001). CONCLUSIONS: Visualization and quantification of CMR coronary CE by CNR and total CE area could be utilized to detect subclinical and clinical coronary wall involvement, which is prevalent in IgG4-RD. The potential inclusion of small and medium-sized vessel involvements in the assessment of disease activity in IgG4-RD is worthy of further investigation.

Evaluation of atmospheric particulate matter pollution characteristics in Shanghai based on biomagnetic monitoring technology.

Atmospheric particulate matter (PM) pollution is one of the world's most serious environmental challenges, and it poses a significant threat to environmental quality and human health. Biomagnetic monitoring of PM has great potential to improve spatial resolution and provide alternative indicators for large area measurements, with respect and complementary to standard air quality monitoring stations. In this study, 160 samples of evergreen plant leaves were collected from park green spaces within five different functional areas of Shanghai. Magnetic properties were investigated to understand the extent and nature of particulate pollution and the possible sources, and to assess the suitability of various plant leaves for urban particulate pollution monitoring. The results showed that magnetic particles of the plant leaf-adherent PM were predominantly composed of pseudo-single domain (PSD) and multi-domain (MD) ferrimagnetic particles. Magnolia grandiflora, as a large evergreen arbor with robust PM retention capabilities, proved to be a more suitable candidate for monitoring urban particulate pollution compared to Osmanthus fragrans, a small evergreen arbor, and Aucuba japonica Thunb. var. variegata and Photinia serratifolia, evergreen shrubs. Meanwhile, there were significant differences in the spatial distribution of the magnetic particle content and heavy metal enrichment of the samples, mainly showing regional variations of industrial area > traffic area > commercial area > residential area > clean area. Additionally, the combination with the results of scanning electron microscopy, shows that industrial production (metal smelting, coal burning), transport and other activities are the main sources of particulate pollution. Plant leaves can be used as an effective tool for urban particulate pollution monitoring and assessment of atmospheric particulate pollution characteristics, and the technique provided useful information on particle size, mineralogy and possible sources.

Mobilizing endogenous neuroprotection: the mechanism of the protective effect of acupuncture on the brain after stroke.

Given its high morbidity, disability, and mortality rates, ischemic stroke (IS) is a severe disease posing a substantial public health threat. Although early thrombolytic therapy is effective in IS treatment, the limited time frame for its administration presents a formidable challenge. Upon occurrence, IS triggers an ischemic cascade response, inducing the brain to generate endogenous protective mechanisms against excitotoxicity and inflammation, among other pathological processes. Stroke patients often experience limited recovery stages. As a result, activating their innate self-protective capacity [endogenous brain protection (EBP)] is essential for neurological function recovery. Acupuncture has exhibited clinical efficacy in cerebral ischemic stroke (CIS) treatment by promoting the human body's self-preservation and "Zheng Qi" (a term in traditional Chinese medicine (TCM) describing positive capabilities such as self-immunity, self-recovery, and disease prevention). According to research, acupuncture can modulate astrocyte activity, decrease oxidative stress (OS), and protect neurons by inhibiting excitotoxicity, inflammation, and apoptosis via activating endogenous protective mechanisms within the brain. Furthermore, acupuncture was found to modulate microglia transformation, thereby reducing inflammation and autoimmune responses, as well as promoting blood flow restoration by regulating the vasculature or the blood-brain barrier (BBB). However, the precise mechanism underlying these processes remains unclear. Consequently, this review aims to shed light on the potential acupuncture-induced endogenous neuroprotective mechanisms by critically examining experimental evidence on the preventive and therapeutic effects exerted by acupuncture on CIS. This review offers a theoretical foundation for acupuncture-based stroke treatment.

Protein tyrosine phosphatases: emerging role in cancer therapy resistance.

BACKGROUND: Tyrosine phosphorylation of intracellular proteins is a post-translational modification that plays a regulatory role in signal transduction during cellular events. Dephosphorylation of signal transduction proteins caused by protein tyrosine phosphatases (PTPs) contributed their role as a convergent node to mediate cross-talk between signaling pathways. In the context of cancer, PTP-mediated pathways have been identified as signaling hubs that enabled cancer cells to mitigate stress induced by clinical therapy. This is achieved by the promotion of constitutive activation of growth-stimulatory signaling pathways or modulation of the immune-suppressive tumor microenvironment. Preclinical evidences suggested that anticancer drugs will release their greatest therapeutic potency when combined with PTP inhibitors, reversing drug resistance that was responsible for clinical failures during cancer therapy. AREAS COVERED: This review aimed to elaborate recent insights that supported the involvement of PTP-mediated pathways in the development of resistance to targeted therapy and immune-checkpoint therapy. EXPERT OPINION: This review proposed the notion of PTP inhibition in anticancer combination therapy as a potential strategy in clinic to achieve long-term tumor regression. Ongoing clinical trials are currently underway to assess the safety and efficacy of combination therapy in advanced-stage tumors.

[Application of modified acetabular anteversion and inclination angles test system in patients undergoing total hip arthroplasty after lumbar fusion].

Objective: To investigate the accuracy and effectiveness of acetabular cup placement in total hip arthroplasty (THA) after lumbar fusion applying of modified acetabular anteversion and inclination angles test system. Methods: A clinical data of 45 patients undergoing THA for osteoarthritis between January 2018 and June 2023 was retrospectively analyzed. All patients had previously received lumbar fusion. The modified acetabular anteversion and inclination angle test system was used in 26 cases (observation group) and not used in 19 cases (control group) during THA. There was no significant difference in baseline data such as gender, age, body mass index, operative side, number of lumbar fusion segments, and preoperative Harris score between the two groups ( P>0.05). The position of acetabular prosthesis, hip function (Harris score), and incidence of complications were compared between the two groups. Results: In the observation group, all acetabular cups were in the safe zone (anteversion angle, 25°-30°) during operation, and 1 acetabular cup (3.85%) was not in the safe zone after operation. In the control group, 9 acetabular cups (47.37%) were not in the safe zone. The postoperative difference between the two groups was significant ( P<0.05). There was no significant difference between intra- and post-operative acetabular inclination angles in the observation group ( P>0.05), and the postoperative acetabular inclination angle was significantly smaller in the observation group than in the control group ( P<0.05). All incisions healed by first intention and no infection occurred. All patients were followed up 6 months. There was no significant difference in Harris score between the two groups at different time point ( P>0.05), and there were significant differences between different time points in the two groups ( P<0.05). No joint dislocation occurred in the observation group during follow-up, while dislocation occurred in 2 cases and femoral impingement syndrome occurred in 1 case of the control group. There was no significant difference in the incidence of complications between the two groups ( P>0.05). Conclusion: For THA patients with lumbar fusion, the ideal placement angle of the acetabular cup can be obtained by using the modified acetabular anteversion and inclination angles test system during operation.

Interface Passivation of a Pyridine-Based Bifunctional Molecule for Inverted Perovskite Solar Cells.

Organic-inorganic hybrid perovskite solar cells (PSCs) have recently been demonstrated to be promising renewable harvesters because of their prominent photovoltaic power conversion efficiency (PCE), although their stability and efficiency still have not reached commercial criteria. Trouble-oriented analyses showcase that defect reduction among the grain boundaries and interfaces in the prepared perovskite polycrystalline films is a practical strategy, which has prompted researchers to develop functional molecules for interface passivation. Herein, the pyridine-based bifunctional molecule dimethylpyridine-3,5-dicarboxylate (DPDC) was employed as the interface between the electron-transport layer and perovskite layer, which achieved a champion PCE of 21.37% for an inverted MAPbI3-based PSC, which was greater than 18.64% for the control device. The mechanistic studies indicated that the significantly improved performance was mainly attributed to the remarkably enhanced fill factor with a value greater than 83%, which was primarily due to the nonradiative recombination suppression offered by the passivation effect of DPDC. Moreover, the promoted carrier mobility together with the enlarged crystal size contributed to a higher short-circuit current density. In addition, an increase in the open-circuit voltage was also observed in the DPDC-treated PSC, which benefited from the improved work function for reducing the energy loss during carrier transport. Furthermore, the DPDC-treated PSC showed substantially enhanced stability, with an over 80% retention rate of its initial PCE value over 300 h even at a 60% relative humidity level, which was attributed to the hydrophobic nature of the DPDC molecule and effective defect passivation. This work is expected not only to serve as an effective strategy for using a pyridine-based bifunctional molecule to passivate perovskite interfaces to enhance photovoltaic performance but also to shed light on the interface passivation mechanism.

Solid-Emission-Tunable Squaraine with Thermal-Promoted Aggregate-State Transitions for Fast Thermal History Sensing.

Determining thermal history is crucial in many industrial processes, but reliable and sensitive organic thermal history indicators are currently absent. Herein, we report on the development of a squaraine-based fluorescent molecule, DPEA-SQ, for the detection of thermal exposure histories up to 436 K. DPEA-SQ forms multiple single crystals (DPEA-SQ-I, DPEA-SQ-II, and DPEA-SQ-III) with different conformations and aggregate-state packing modes, contributing to their different fluorescence wavelengths, lifetimes, and efficiencies. Interestingly, DPEA-SQ-I and DPEA-SQ-III undergo aggregate-state structural transitions to form the thermodynamically more stable DPEA-SQ-II, which are accompanied by changes in their fluorescence. By taking advantage of similar aggregate-state structural transformations during heating, a high-temperature thermal exposure history of up to 436 K is recorded and reflected by their fluorescence. To demonstrate the potential practical applications of DPEA-SQ, a DPEA-SQ-Powder/PDMS film is prepared and coated on an electric circuit board, which enables real-time monitoring of localized overheating by the naked eye. Additionally, the fluorescence peaks of DPEA-SQ-Powder and DPEA-SQ-Powder/PDMS films remain unchanged after storage at 373 K for 52 days, demonstrating high aggregate-state stability. The fast and reliable responses of this system make it an excellent candidate for the detection of overtemperature traces in electronic components and circuit diagnosis.

Development of Attenuated Viruses for Effective Protection against Pepper Veinal Mottle Virus in Tomato Crops.

Tomato (Solanum lycopersicum) is the most important vegetable and fruit crop in the family Solanaceae worldwide. Numerous pests and pathogens, especially viruses, severely affect tomato production, causing immeasurable market losses. In Taiwan, the cultivation of tomato crops is mainly threatened by insect-borne viruses, among which pepper veinal mottle virus (PVMV) is one of the most prevalent. PVMV is a member of the genus Potyvirus of the family Potyviridae and is non-persistently transmitted by aphids. Its infection significantly reduces tomato fruit yield and quality. So far, no PVMV-resistant tomato lines are available. In this study, we performed nitrite-induced mutagenesis of the PVMV tomato isolate Tn to generate attenuated PVMV mutants. PVMV Tn causes necrotic lesions in Chenopodium quinoa leaves and severe mosaic and wilting in Nicotiana benthamiana plants. After nitrite treatment, three attenuated PVMV mutants, m4-8, m10-1, and m10-11, were selected while inducing milder responses to C. quinoa and N. benthamiana with lower accumulation in tomato plants. In greenhouse tests, the three mutants showed different degrees of cross-protection against wild-type PVMV Tn. m4-8 showed the highest protective efficacy against PVMV Tn in N. benthamiana and tomato plants, 100% and 97.9%, respectively. A whole-genome sequence comparison of PVMV Tn and m4-8 revealed that 20 nucleotide substitutions occurred in the m4-8 genome, resulting in 18 amino acid changes. Our results suggest that m4-8 has excellent potential to protect tomato crops from PVMV. The application of m4-8 in protecting other Solanaceae crops, such as peppers, will be studied in the future.

Mammalian IRE1α dynamically and functionally coalesces with stress granules.

Upon endoplasmic reticulum (ER) stress, activation of the ER-resident transmembrane protein kinase/endoribonuclease inositol-requiring enzyme 1 (IRE1) initiates a key branch of the unfolded protein response (UPR) through unconventional splicing generation of the transcription factor X-box-binding protein 1 (XBP1s). Activated IRE1 can form large clusters/foci, whose exact dynamic architectures and functional properties remain largely elusive. Here we report that, in mammalian cells, formation of IRE1α clusters is an ER membrane-bound phase separation event that is coupled to the assembly of stress granules (SGs). In response to different stressors, IRE1α clusters are dynamically tethered to SGs at the ER. The cytosolic linker portion of IRE1α possesses intrinsically disordered regions and is essential for its condensation with SGs. Furthermore, disruption of SG assembly abolishes IRE1α clustering and compromises XBP1 mRNA splicing, and such IRE1α-SG coalescence engenders enrichment of the biochemical components of the pro-survival IRE1α-XBP1 pathway during ER stress. Our findings unravel a phase transition mechanism for the spatiotemporal assembly of IRE1α-SG condensates to establish a more efficient IRE1α machinery, thus enabling higher stress-handling capacity.

Small molecule inhibitors targeting m6A regulators.

As the most common form of epigenetic regulation by RNA, N6 methyladenosine (m6A) modification is closely involved in physiological processes, such as growth and development, stem cell renewal and differentiation, and DNA damage response. Meanwhile, its aberrant expression in cancer tissues promotes the development of malignant tumors, as well as plays important roles in proliferation, metastasis, drug resistance, immunity and prognosis. This close association between m6A and cancers has garnered substantial attention in recent years. An increasing number of small molecules have emerged as potential agents to target m6A regulators for cancer treatment. These molecules target the epigenetic level, enabling precise intervention in RNA modifications and efficiently disrupting the survival mechanisms of tumor cells, thus paving the way for novel approaches in cancer treatment. However, there is currently a lack of a comprehensive review on small molecules targeting m6A regulators for anti-tumor. Here, we have comprehensively summarized the classification and functions of m6A regulators, elucidating their interactions with the proliferation, metastasis, drug resistance, and immune responses in common cancers. Furthermore, we have provided a comprehensive overview on the development, mode of action, pharmacology and structure-activity relationships of small molecules targeting m6A regulators. Our aim is to offer insights for subsequent drug design and optimization, while also providing an outlook on future prospects for small molecule development targeting m6A.

A tunable ultra-broadband and ultra-high sensitivity far-infrared metamaterial absorber based on VO2 and graphene.

We proposed a far-infrared tunable metamaterial absorber using vanadium dioxide (VO2) and graphene as controlling materials. The properties of the absorber are investigated theoretically using the finite-difference time-domain (FDTD) technique. It was found that when the Fermi energy level of graphene is fixed at zero, VO2 is in the insulated state, and the metasurface exhibits far-infrared broadband absorption performance, with absorptance exceeding 90% in the wavelength range of 12.6 µm to 23.2 µm. In addition, by elevating the Fermi energy level of graphene, the absorption bandwidth of the device is expanded continuously. When the VO2 is in the metallic state, the device can flexibly transform into a far-infrared narrowband absorber. The device also has the advantage of being insensitive to changes in polarization and incident angle. The origin of the absorption and the tuning principle of the device were analyzed and verified successfully by using an equivalent circuit model (ECM). Besides, we also studied the refraction index sensing characteristics of the absorber. Surprisingly, the absorber exhibits excellent sensing characteristics, and its sensitivity (S) reaches 14.108 µm per RIU and the figure of merit (FOM) is 6.13 per RIU.

Rethinking therapeutic strategies of dual-target drugs: An update on pharmacological small-molecule compounds in cancer.

Oncogenes and tumor suppressors are well-known to orchestrate several signaling cascades, regulate extracellular and intracellular stimuli, and ultimately control the fate of cancer cells. Accumulating evidence has recently revealed that perturbation of these key modulators by mutations or abnormal protein expressions are closely associated with drug resistance in cancer therapy; however, the inherent drug resistance or compensatory mechanism remains to be clarified for targeted drug discovery. Thus, dual-target drug development has been widely reported to be a promising therapeutic strategy for improving drug efficiency or overcoming resistance mechanisms. In this review, we provide an overview of the therapeutic strategies of dual-target drugs, especially focusing on pharmacological small-molecule compounds in cancer, including small molecules targeting mutation resistance, compensatory mechanisms, synthetic lethality, synergistic effects, and other new emerging strategies. Together, these therapeutic strategies of dual-target drugs would shed light on discovering more novel candidate small-molecule drugs for the future cancer treatment.

A fully validated LC­MS/MS method for quantifying bevacizumab in plasma samples from patients with NSCLC and its implications in therapeutic drug monitoring.

Given the increasing use of bevacizumab in combinatorial drug therapy for a multitude of different cancer types, there is a need for therapeutic drug monitoring to analyze the possible correlation between drug trough concentration, and therapeutic effect and adverse reactions. An ultra-performance liquid chromatography tandem-mass spectrometry method was then developed and validated to determine bevacizumab levels in human plasma samples. Chromatographic separation was achieved on a Shimadzu InertSustainBio C18 HP column, whereas subsequent mass spectrometric analysis was performed using a Shimadzu 8050CL triple quadrupole mass spectrometer equipped with an electro-spray ionization source in the positive ion mode. In total, three multiple reaction monitoring transitions of each of the surrogate peptides were chosen with 'FTFSLDTSK' applied as the quantification peptide whereas 'VLIYFTSSLHSGVPSR' and 'STAYLQMNSLR' were designated as the verification peptides using the Skyline software. This analytical method was then fully validated, with specificity, linearity, lower limit of quantitation, accuracy, precision, stability, matrix effect and recovery calculated. The linearity of this method was developed to be within the concentration range 5-400 µg/ml for bevacizumab in human plasma. Subsequently, eight patients with non-small cell lung cancer (NSCLC) were recruited and injected with bevacizumab over three periods of treatment to analyze their steady-state trough concentration and differences. To conclude, the results of the present study suggest that bevacizumab can be monitored in a therapeutic setting in patients with NSCLC.

A TLR4-Targeting Bioactive Peptide Hydrogel to Regulate Immune-Microenvironment for Diabetic Wound Repair.

Persistent inflammation and disrupted immunoregulation are critical factors in impeding diabetic wound healing. While immunoregulatory hydrogel dressings hold significant promise for clinical applications in diabetic wound healing, the current application often demands intricate interventions and high-cost treatments involving cytokines and cell therapies. The development of single component immunoregulatory hydrogels remains a complex challenge. To address this issue, an active peptide hydrogel with immunoregulatory properties targeting the TLR4/NF-kB pathway, aiming to promote rapid diabetic wound healing, is engineered. The hydrogel sequence comprises naphthalene derivative, phenylalanine, and glycine to modulate hydrophilic/hydrophobic characteristics. The amino group on arginine contributes to tissue adhesion and regulation of intermolecular forces, ultimately yielding stable gels. The results underscore the formation of the peptide hydrogel (NFA) via the physical crosslinking of self-assembled nanofibers in water, thereby affording both excellent injectability and tissue adhesion. Notably, NFA demonstrates significant potential in promoting wound healing in a mouse model with full-thickness wounds by regulating macrophage responses in the inflammatory microenvironment through the TLR4/NF-kB pathway.

Discovery of a novel small-molecule activator of SIRT3 that inhibits cell proliferation and migration by apoptosis and autophagy-dependent cell death pathways in colorectal cancer.

Colorectal cancer (CRC) is well known as a prevalent malignancy affecting the digestive tract, yet its precise etiological determinants remain to be elusive. Accordingly, identifying specific molecular targets for colorectal cancer and predicting potential malignant tumor behavior are potential strategies for therapeutic interventions. Of note, apoptosis (type I programmed cell death) has been widely reported to play a pivotal role in tumorigenesis by exerting a suppressive effect on cancer development. Moreover, autophagy-dependent cell death (type II programmed cell death) has been implicated in different types of human cancers. Thus, investigating the molecular mechanisms underlying apoptosis and autophagy-dependent cell death is paramount in treatment modalities of colorectal cancer. In this study, we uncovered that a new small-molecule activator of SIRT3, named MY-13, triggered both autophagy-dependent cell death and apoptosis by modulating the SIRT3/Hsp90/AKT signaling pathway. Consequently, this compound inhibited tumor cell proliferation and migration in RKO and HCT-116 cell lines. Moreover, we further demonstrated that the small-molecule activator significantly suppressed tumor growth in vivo. In conclusion, these findings demonstrate that the novel small-molecule activator of SIRT3 may hold a therapeutic potential as a drug candidate in colorectal cancer.

Investigation on Mechanism of Microstructure Evolution during Multi-Process Hot Forming of GH4169 Superalloy Forging.

Typically, in the manufacturing of GH4169 superalloy forgings, the multi-process hot forming that consists of pre-deformation, heat treatment and final deformation is required. This study focuses on the microstructural evolution throughout hot working processes. Considering that δ phase can promote nucleation and limit the growth of grains, a process route was designed, including pre-deformation, aging treatment (AT) to precipitate sufficient δ phases, high temperature holding (HTH) to uniformly heat the forging, and final deformation. The results show that the uneven strain distribution after pre-deformation has a significant impact on the subsequent refinement of the grain microstructure due to the complex coupling relationship between the evolution of the δ phase and recrystallization behavior. After the final deformation, the fine-grain microstructure with short rod-like δ phases as boundaries is easy to form in the region with a large strain of the pre-forging. However, necklace-like mixed grain microstructure is formed in the region with a small strain of the pre-forging. In addition, when the microstructure before final deformation consists of mixed grains, dynamic recrystallization (DRX) nucleation behavior preferentially depends on kernel average misorientation (KAM) values. A large KAM can promote the formation of DRX nuclei. When the KAM values are close, a smaller average grain size of mixed-grain microstructure is more conductive to promote the DRX nucleation. Finally, the interaction mechanisms between δ phase and DRX nucleation are revealed.

Aggressive vertebral hemangiomas contain no adipose tissue resulting in thoracic spine kyphosis: A case report.

RATIONALE: Aggressive vertebral hemangiomas (AVHs) destroy continuous vertebral bodies and intervertebral discs and resulting in spinal kyphosis is extremely rare. The very aggressive behavior was attributable to its significant vascular component and contained no adipose tissue. PATIENT CONCERNS: We report a case of thoracic spine kyphosis of AVHs with multiple vertebral bodies and intervertebral disc destruction in a 45-year-old woman. DIAGNOSES: Based on the imaging studies, the patient underwent surgical removal of this lesion and spinal reconstruction. Histopathology consistent with vertebral hemangioma and contained no adipose. INTERVENTIONS: The patient underwent surgical removal of the lesion and spinal reconstruction. After subperiosteal dissection of the paraspinal muscles and exposure of the laminae, the laminae of the T5-7 vertebrae were removed and exposing the lesion. The lesion was soft and showed cystic changes, completely curetted and autogenous bone was implanted. Vertebroplasty was performed through T3-T9 pedicles bilaterally. Pedicle screw fixation was performed for segmental fixation and fusion. OUTCOMES: After 9 days of operation, the incision healed cleanly and free of pain. She was discharged in good general condition. The patient remained asymptomatic after follow-up 6 months of postoperative. LESSONS: AVHs destroy multiple vertebral bodies and intervertebral discs and resulting in spinal kyphosis is extremely rare.

Independence Threat or Interdependence Threat? The Focusing Effect on Social or Physical Threat Modulates Brain Activity.

OBJECTIVE: The neural basis of threat perception has mostly been examined separately for social or physical threats. However, most of the threats encountered in everyday life are complex. The features of interactions between social and physiological threats under different attentional conditions are unclear. METHOD: The present study explores this issue using an attention-guided paradigm based on ERP techniques. The screen displays social threats (face threats) and physical threats (action threats), instructing participants to concentrate on only one type of threat, thereby exploring brain activation characteristics. RESULTS: It was found that action threats did not affect the processing of face threats in the face-attention condition, and electrophysiological evidence from the brain suggests a comparable situation to that when processing face threats alone, with higher amplitudes of the N170 and EPN (Early Posterior Negativity) components of anger than neutral emotions. However, when focusing on the action-attention condition, the brain was affected by face threats, as evidenced by a greater N190 elicited by stimuli containing threatening emotions, regardless of whether the action was threatening or not. This trend was also reflected in EPN. CONCLUSIONS: The current study reveals important similarities and differences between physical and social threats, suggesting that the brain has a greater processing advantage for social threats.

Association of autoimmune and allergic diseases with senile cataract: a bidirectional two-sample Mendelian randomization study.

Background: Many observational studies have been reported that patients with autoimmune or allergic diseases seem to have a higher risk of developing senile cataract, but the views are not consistent. In order to minimize the influence of reverse causality and potential confounding factors, we performed Mendelian Randomization (MR) analysis to investigate the genetic causal associations between autoimmune, allergic diseases and senile cataract. Methods: Single nucleotide polymorphisms associated with ten common autoimmune and allergic diseases were obtained from the IEU Open genome-wide association studies (GWAS) database. Summary-level GWAS statistics for clinically diagnosed senile cataract were obtained from the FinnGen research project GWAS, which consisted of 59,522 individuals with senile cataracts and 312,864 control individuals. MR analysis was conducted using mainly inverse variance weighted (IVW) method and further sensitivity analysis was performed to test robustness. Results: As for ten diseases, IVW results confirmed that type 1 diabetes (OR = 1.06; 95% CI = 1.05-1.08; p = 2.24×10-12), rheumatoid arthritis (OR = 1.05; 95% CI = 1.02-1.08; p = 1.83×10-4), hypothyroidism (OR = 2.4; 95% CI = 1.42-4.06; p = 1.12×10-3), systemic lupus erythematosus (OR = 1.02; 95% CI = 1.01-1.03; p = 2.27×10-3), asthma (OR = 1.02; 95% CI = 1.01-1.03; p = 1.2×10-3) and allergic rhinitis (OR = 1.07; 95% CI = 1.02-1.11; p = 2.15×10-3) were correlated with the risk of senile cataract. Celiac disease (OR = 1.04; 95% CI = 1.01-1.08; P = 0.0437) and atopic dermatitis (OR = 1.05; 95% CI = 1.01-1.10; P = 0.0426) exhibited a suggestive connection with senile cataract after Bonferroni correction. These associations are consistent across weighted median and MR Egger methods, with similar causal estimates in direction and magnitude. Sensitivity analysis further proved that these associations were reliable. Conclusions: The results of the MR analysis showed that there were causal relationships between type 1 diabetes, rheumatoid arthritis, hypothyroidism, systemic lupus erythematosus, asthma, allergic rhinitis and senile cataract. To clarify the possible role of autoimmune and allergy in the pathophysiology of senile cataract, further studies are needed.

Manipulation of Nonradiative Process Based on the Aggregation Microenvironment to Customize Excited-State Energy Conversion.

ConspectusNonradiative processes with the determined role in excited-state energy conversion, such as internal conversion (IC), vibrational relaxation (VR), intersystem crossing (ISC), and energy or electron transfer (ET or eT), have exerted a crucial effect on biological functions in nature. Inspired by these, nonradiative process manipulation has been extensively utilized to develop organic functional materials in the fields of energy and biomedicine. Therefore, comprehensive knowledge and effective manipulation of sophisticated nonradiative processes for achieving high-efficiency excited-state energy conversion are quintessential. So far, many strategies focused on molecular engineering have demonstrated tremendous potential in manipulating nonradiative processes to tailor excited-state energy conversion. Besides, molecular aggregation considerably affects nonradiative processes due to their ultrasensitivity, thus providing us with another essential approach to manipulating nonradiative processes, such as the famous aggregation-induced emission. However, the weak interactions established upon aggregation, namely, the aggregation microenvironment (AME), possess hierarchical, dynamic, and systemic characteristics and are extremely complicated to elucidate. Revealing the relationship between the AME and nonradiative process and employing it to customize excited-state energy conversion would greatly promote advanced materials in energy utilization, biomedicine, etc., but remain a huge challenge. Our group has devoted much effort to achieving this goal.In this Account, we focus on our recent developments in nonradiative process manipulation based on AME. First, we provide insight into the effect of the AME on nonradiative process in terms of its steric effect and electronic regulation, illustrating the possibility of nonradiative process manipulation through AME modulation. Second, the distinct enhanced steric effect is established by crystallization and heterogeneous polymerization to conduct crystallization-induced reversal from dark to bright excited states and dynamic hardening-triggered nonradiative process suppression for highly efficient luminescence. Meanwhile, promoting the ISC process and stabilizing the triplet state are also manipulated by the crystal and polymer matrix to induce room-temperature phosphorescence. Furthermore, the strategies employed to exploit nonradiative processes for photothermy and photosensitization are reviewed. For photothermal conversion, besides the weakened steric effect with promoted molecular motions, a new strategy involving the introduction of diradicals upon aggregation to narrow the energy band gap and enhance intermolecular interactions is put forward to facilitate IC and VR for high-efficiency photothermal conversion. For photosensitization, both the enhanced steric effect from the rigid matrix and the effective electronic regulation from the electron-rich microenvironment are demonstrated to facilitate ISC, ET, and eT for superior photosensitization. Finally, we explore the existing challenges and future directions of nonradiative process manipulation by AME modulation for customized excited-state energy conversion. We hope that this Account will be of wide interest to readers from different disciplines.