Photo-Amplified Plasma Membrane Rupture by Membrane-Anchoring NIR-II Small Molecule Design for Improved Cancer Photoimmunotherapy.

Immunotherapy is a promising cancer treatment method for eradicating tumor cells by enhancing the immune response. However, there are several major obstacles to conventional phototherapy-mediated immune responses, including inadequate immunogenicity and immunosuppressive environment. Here, we present a novel photoimmunotherapy modality-the development of membrane-anchoring small molecule inducing plasma membrane rupture (PMR) by NIR-II photo-stimulation, thus evoking cell necrotic death and enhancing antitumor immunotherapy. Our top-performing membrane-anchoring small molecule (CBT-3) exhibits temperature-tunable PMR efficiency, allowing rapid necrotic death in cancer cells at 50 µM dose by using exogenous NIR-II light-mediated mild photothermal effect (1064 nm, 0.6 W cm-2). Further evidence indicated that this gentle therapeutic approach activated inflammatory signaling pathways in cells, enhanced immunogenic cell death, and reshaped the immunosuppressive tumor microenvironment, ultimately promoting systemic antitumor immune responses in vivo. This study represents the first instance of utilizing NIR-II photo-amplified PMR effect based on membrane-anchoring small molecule, providing a novel avenue for advancing cancer photoimmunotherapy.

Stabilization of dimeric PYR/PYL/RCAR family members relieves abscisic acid-induced inhibition of seed germination.

Abscisic acid (ABA) is the primary preventing factor of seed germination, which is crucial to plant survival and propagation. ABA-induced seed germination inhibition is mainly mediated by the dimeric PYR/PYL/RCAR (PYLs) family members. However, little is known about the relevance between dimeric stability of PYLs and seed germination. Here, we reveal that stabilization of PYL dimer can relieve ABA-induced inhibition of seed germination using chemical genetic approaches. Di-nitrobensulfamide (DBSA), a computationally designed chemical probe, yields around ten-fold improvement in receptor affinity relative to ABA. DBSA reverses ABA-induced inhibition of seed germination mainly through dimeric receptors and recovers the expression of ABA-responsive genes. DBSA maintains PYR1 in dimeric state during protein oligomeric state experiment. X-ray crystallography shows that DBSA targets a pocket in PYL dimer interface and may stabilize PYL dimer by forming hydrogen networks. Our results illustrate the potential of PYL dimer stabilization in preventing ABA-induced seed germination inhibition.

Designing Zero-Dimensional Cadmium-Based Organic-Inorganic Hybrids: The Role of Halogen Doping in Modulating Multifunctional Properties.

Advances in materials science are increasingly dependent on the development of multifunctional materials capable of improving system efficiency and reducing the environmental impact. In this study, two zero-dimensional (0D) cadmium-based organic-inorganic hybrid materials (BEMPD)2CdBr4 (BEMPD-Br, 1) and (BEMPD)2CdBr2Cl2 (BEMPD-ClBr, 2) (BEMPD = 1-(2-bromoethyl)-1-methylpiperidine) were prepared by halogen doping. Compound 2 is a mixed halide in which there are two halogen sites, Cl and Br, and in a disordered state, which has a regulatory effect on the structural distortion and properties of the compound. The Curie temperatures of compounds 1 and 2 are 348 and 390 K, respectively, and the UV-vis absorption spectra showed that the direct band gaps of compounds 1 and 2 were 4.68 and 4.8 eV, respectively. In addition, room-temperature photoluminescence experiments show broadband emission peaks at 717 and 683 nm for compounds 1 and 2, respectively, with fluorescence lifetimes of 2.414 and 3.915 µs. These 0D hybrids provide an avenue for the development of smart materials and optoelectronic devices, and also provide positive clues for manipulating the properties of organic-inorganic hybrid compounds.

Unraveling stroke gait deviations with movement analytics, more than meets the eye: a case control study.

Background: This study aimed to identify and quantify the kinematic and kinetic gait deviations in post-stroke hemiplegic patients with matched healthy controls using Statistical Parametric Mapping (SPM). Methods: Fifteen chronic stroke patients [4 females, 11 males; age 53.7 (standard deviation 12.2) years; body mass 65.4 (10.4) kg; standing height 168.5 (9.6) cm] and 15 matched healthy controls [4 females, 11 males; age 52.9 (11.7) years; body weight 66.5 (10.7) years; standing height 168.3 (8.8) cm] were recruited. In a 10-m walking task, joint angles, ground reaction forces (GRF), and joint moments were collected, analyzed, and compared using SPM for an entire gait cycle. Results: Generally, when comparing the stroke patients' affected (hemiplegic) and less-affected (contralateral) limbs with the control group, SPM identified significant differences in the late stance phase and early swing phase in the joint angles and moments in bilateral limbs (all p < 0.005). In addition, the vertical and anteroposterior components of GRF were significantly different in various periods of the stance phase (all p < 0.005), while the mediolateral component showed no differences between the two groups. Conclusion: SPM was able to detect abnormal gait patterns in both the affected and less-affected limbs of stroke patients with significant differences when compared with matched controls. The findings draw attention to significant quantifiable gait deviations in the less-affected post-stroke limb with the potential impact to inform gait retraining strategies for clinicians and physiotherapists.

Molecular insights into the functional analysis of P450 CYP321A7 gene in the involvement of detoxification of lambda-cyhalothrin in Spodoptera frugiperda.

Fall armyworm, Spodoptera frugiperda (J. E. Smith), is a widely recognized global agricultural pest that has significantly reduced crop yields all over the world. S. frugiperda has developed resistance to various insecticides. Insect cytochrome P450 monooxygenases (CYPs or P450s) play an important role in detoxifying insecticides, leading to increased resistance in insect populations. However, the function of the specific P450 gene for lambda-cyhalothrin resistance in S. frugiperda was unclear. Herein, the expression patterns of 40 P450 genes in the susceptible and lambda-cyhalothrin-resistant populations were analyzed. Among them, CYP321A7 was found to be overexpressed in the resistant population, specifically LRS (resistance ratio = 25.38-fold) derived from a lambda-cyhalothrin-susceptible (SS) population and FLRS (a population caught from a field, resistance ratio = 63.80-fold). Elevated enzyme activity of cytochrome P450 monooxygenases (P450s) was observed for LRS (2.76-fold) and the FLRS (4.88-fold) as compared to SS, while no significant differences were observed in the activities of glutathione S-transferases and esterases. Furthermore, the knockdown of CYP321A7 gene by RNA interference significantly increased the susceptibility to lambda-cyhalothrin. Remarkably, the knockdown of CYP321A7 reduced the enzymatic activity of P450 by 43.7%, 31.9%, and 22.5% in SS, LRS, and FLRS populations, respectively. Interestingly, fourth-instar larvae treated with lambda-cyhalothrin at the LC30 dosage had a greater mortality rate due to RNA interference-induced suppression of CYP321A7 (with increases of 61.1%, 50.0%, and 45.6% for SS, LRS, and FLRS populations, respectively). These findings suggest a link between lambda-cyhalothrin resistance and continual overexpression of CYP321A7 in S. frugiperda larvae, emphasizing the possible importance of CYP321A7 in lambda-cyhalothrin detoxification in S. frugiperda.

Extending the emission peak tail of indole cyanine for deep-near-infrared bioimaging.

We propose a novel strategy for tailoring the structure of fluorescent molecules to achieve emission at the tail end of the NIR-II window. The favorable spectroscopic properties and low cytotoxicity of YNs make them powerful tools for bioimaging. Notably, YN-4 exhibits a brightness 2.5 times greater than YN-3, 6 times that of IR-783, and 5 times that of ICG. This enhanced brightness enabled high-resolution imaging of mouse thoracic and abdominal cavities, tumor vasculature, and real-time monitoring of gastrointestinal motility using YN-4. Furthermore, covalent grafting of glucose onto the YN-Glu scaffold significantly improved tumor-targeting capability and facilitated tracking of glucose metabolism. This work aims to extend the application of fluorescent molecule imaging beyond the NIR-IIa window.

Active visual continuous seam tracking based on adaptive feature detection and particle filter tracking.

Welding seam tracking based on online programming is the future trend of intelligent production. However, most of the existing image processing methods have certain limitations in the adaptability, accuracy, and robustness of weld feature point detection. The online welding method of gas metal arc welding (GMAW) based on active vision sensing is studied in this paper. The Steger sub-pixel detection method is used to guarantee the accuracy of feature point extraction, and a self-adaptive search window and self-adaptive slope extraction are proposed on this basis. The self-adaptive window is generated according to the linear information of the weld area, and the scale factor and range threshold constraint are added to realize the real-time detection of the weld feature information. Screening the center pixel of the laser stripe in the self-adaptive window of the current frame by the initial slope or the self-adaptive slope of the previous frame, the linear information of the weld area is obtained. The self-adaptive slope of the current frame is fitted by the random sampling consistency method, and the pixel margin is retained to adapt to the linear detection of different continuous welds. When arc light and other serious interference make it difficult to obtain weld information, a particle filter is used to make the best prediction of the weld position. Finally, the welding robot platform based on laser vision sensing was built to test various continuous welds of the butt weld, fillet weld, and lap weld. Experimental results show that the detection speed is 27 ms, and the accuracy of detection and tracking can respectively reach 0.03 mm and 0.78 mm, which meets the requirements of weld detection and tracking.

Relationship of serial muscle ultrasound of rectus femoris and ambulatory recovery in patients with acute incomplete spinal cord injury: A prospective observational study.

CONTEXT/OBJECTIVE: To investigate the change in serial muscle ultrasound of rectus femoris of patients with incomplete spinal cord injury (SCI) performed within 2 months after SCI during acute rehabilitation, and the relationship with functional outcomes at 1 year post-injury. DESIGN: Prospective observational study. SETTING: Inpatient multi-speciality tertiary rehabilitation center in Singapore. PARTICIPANTS: Fifty-four patients with incomplete SCI, defined as American Spinal Injury Association Impairment Scale B-D, with SCI above L2, were recruited from March 2020 to June 2021. Serial muscle ultrasound of the rectus femoris thickness and echo intensity were obtained at 1 week post-injury and after 2 months via standardized protocols. OUTCOME MEASURES: Functional Independence Measure (FIM) motor score, Lower Extremity Motor Score (LEMS), Spinal Cord Independence Measure III (SCIM III) indoor mobility component and Walking Index for Spinal Cord Injury II (WISCI II) were assessed in the first week post-admission and at 1 year. RESULTS: There was a significant positive correlation between change in rectus femoris muscle thickness over 2 months and FIM motor score (P < 0.001), LEMS (P < 0.001), SCIM III indoor mobility component (P < 0.001) and WISCI II (P < 0.001) at 1 year. For the change in echo intensity over 2 months, there was a significantly negative correlation with FIM motor score (P = 0.002), LEMS (P = 0.002), SCIM III indoor mobility component (P = 0.001) and WISCI II (P = 0.001) at 1 year. CONCLUSION: The findings suggest that ultrasonographic serial assessment of rectus femoris muscle thickness and echo intensity during rehabilitation may be useful for determining the long-term functional outcomes in patients with incomplete SCI.

Centralized industrialization of pork in Europe and America contributes to the global spread of Salmonella enterica.

Salmonella enterica causes severe food-borne infections through contamination of the food supply chain. Its evolution has been associated with human activities, especially animal husbandry. Advances in intensive farming and global transportation have substantially reshaped the pig industry, but their impact on the evolution of associated zoonotic pathogens such as S. enterica remains unresolved. Here we investigated the population fluctuation, accumulation of antimicrobial resistance genes and international serovar Choleraesuis transmission of nine pig-enriched S. enterica populations comprising more than 9,000 genomes. Most changes were found to be attributable to the developments of the modern pig industry. All pig-enriched salmonellae experienced host transfers in pigs and/or population expansions over the past century, with pigs and pork having become the main sources of S. enterica transmissions to other hosts. Overall, our analysis revealed strong associations between the transmission of pig-enriched salmonellae and the global pork trade.

MicroRNA expression profile of chicken liver at different times after Histomonas meleagridis infection.

Histomonas meleagridis, an anaerobic intercellular parasite, is known to infect gallinaceous birds, particularly turkeys and chickens. The resurgence of histomonosis in recent times has resulted in significant financial setbacks due to the prohibition of drugs used for disease treatment. Currently, research on about H. meleagridis primarily concentrate on the examination of its virulence, gene expression analysis, and the innate immunity response of the host organism. However, there is a lack of research on differentially expressed miRNAs (DEMs) related to liver infection induced by H. meleagridis. In this study, the weight gain and pathological changes at various post-infection time points were evaluated through animal experiments to determine the peak and early stages of infection. Next, High-throughput sequencing was used to examine the expression profile of liver miRNA at 10 and 15 days post-infection (DPI) in chickens infected with the Chinese JSYZ-F strain of H. meleagridis. A comparison with uninfected controls revealed the presence of 120 and 118 DEMs in the liver of infected chickens at 10 DPI and 15 DPI, respectively, with 74 DEMs being shared between the two time points. Differentially expressed microRNAs (DEMs) were categorized into three groups based on the time post-infection. The first group (L1) includes 45 miRNAs that were differentially expressed only at 10 DPI and were predicted to target 1646 genes. The second group (L2) includes 43 miRNAs that were differentially expressed only at 15 DPI and were predicted to target 2257 genes. The third group (L3) includes 75 miRNAs that were differentially expressed at both 10 DPI and 15 DPI and were predicted to target 1623 genes. At L1, L2, and L3, there were 89, 87, and 41 significantly enriched Gene Ontology (GO) terms, respectively (p<0.05). The analysis of differentially expressed miRNA target genes using KEGG pathways revealed significant enrichment at L1, L2, and L3, with 3, 4, and 5 pathways identified, respectively (p<0.05). This article suggests that the expression of liver miRNA undergoes dynamic alterations due to H. meleagridis and the host. It showed that the expression pattern of L1 class DEMs was more conducive to regulating the development of the inflammatory response, while the L2 class DEMs were more conducive to augmenting the inflammatory response. The observed patterns of miRNA expression associated with inflammation were in line with the liver's inflammatory process following infection. The results of this study provide a basis for conducting a comprehensive analysis of the pathogenic mechanism of H. meleagridis from the perspective of host miRNAs.