Separation of Oral Cooling and Warming Requires TRPM8.

Cooling sensations arise inside the mouth during ingestive and homeostasis behaviors. Oral presence of cooling temperature engages the cold and menthol receptor TRPM8 (transient receptor potential melastatin 8) on trigeminal afferents. Yet, how TRPM8 influences brain and behavioral responses to oral temperature is undefined. Here we used in vivo neurophysiology to record action potentials stimulated by cooling and warming of oral tissues from trigeminal nucleus caudalis neurons in female and male wild-type and TRPM8 gene deficient mice. Using these lines, we also measured orobehavioral licking responses to cool and warm water in a novel, temperature-controlled fluid choice test. Capture of antidromic electrophysiological responses to thalamic stimulation identified that wild-type central trigeminal neurons showed diverse responses to oral cooling. Some neurons displayed relatively strong excitation to cold <10°C (COLD neurons) while others responded to only a segment of mild cool temperatures below 30°C (COOL neurons). Notably, TRPM8 deficient mice retained COLD-type but lacked COOL cells. This deficit impaired population responses to mild cooling temperatures below 30°C and allowed warmth-like (≥35°C) neural activity to pervade the normally innocuous cool temperature range, predicting TRPM8 deficient mice would show anomalously similar orobehavioral responses to warm and cool temperatures. Accordingly, TRPM8 deficient mice avoided both warm (35°C) and mild cool (≤30°C) water and sought colder temperatures in fluid licking tests, whereas control mice avoided warm but were indifferent to mild cool and colder water. Results imply TRPM8 input separates cool from warm temperature sensing and suggest other thermoreceptors also participate in oral cooling sensation.

Electromagnetic Field-Assisted Frozen Tissue Planarization Enhances MALDI-MSI in Plant Spatial Omics.

Plant samples with irregular morphology are challenging for longitudinal tissue sectioning. This has restricted the ability to gain insight into some plants using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). Herein, we develop a novel technique termed electromagnetic field-assisted frozen tissue planarization (EMFAFTP). This technique involves using a pair of adjustable electromagnets on both sides of a plant tissue. Under an optimized electromagnetic field strength, nondestructive planarization and regularization of the frozen tissue is induced, allowing the longitudinal tissue sectioning that favors subsequent molecular profiling by MALDI-MSI. As a proof of concept, flowers, leaves and roots with irregular morphology from six plant species are chosen to evaluate the performance of EMFAFTP for MALDI-MSI of secondary metabolites, amino acids, lipids, and proteins among others in the plant samples. The significantly enhanced MALDI-MSI capabilities of these endogenous molecules demonstrate the robustness of EMFAFTP and suggest it has the potential to become a standard technique for advancing MALDI-MSI into a new era of plant spatial omics.

Development of a baculoviral CRISPR/Cas9 vector system for beta-2-microglobulin knockout in human pluripotent stem cells.

Derivation of hypoimmunogenic human cells from genetically manipulated pluripotent stem cells holds great promise for future transplantation medicine and adoptive immunotherapy. Disruption of beta-2-microglobulin (B2M) in pluripotent stem cells followed by differentiation into specialized cell types is a promising approach to derive hypoimmunogenic cells. Given the attractive features of CRISPR/Cas9-based gene editing tool and baculoviral delivery system, baculovirus can deliver CRISPR/Cas9 components for site-specific gene editing of B2M. Herein, we report the development of a baculoviral CRISPR/Cas9 vector system for the B2M locus disruption in human cells. When tested in human embryonic stem cells (hESCs), the B2M gene knockdown/out was successfully achieved, leading to the stable down-regulation of human leukocyte antigen class I expression on the cell surface. Fibroblasts derived from the B2M gene-disrupted hESCs were then used as stimulator cells in the co-cultures with human peripheral blood mononuclear cells. These fibroblasts triggered significantly reduced alloimmune responses as assessed by sensitive Elispot assays. The B2M-negative hESCs maintained the pluripotency and the ability to differentiate into three germ lineages in vitro and in vivo. These findings demonstrated the feasibility of using the baculoviral-CRISPR/Cas9 system to establish B2M-disrupted pluripotent stem cells. B2M knockdown/out sufficiently leads to hypoimmunogenic conditions, thereby supporting the potential use of B2M-negative cells as universal donor cells for allogeneic cell therapy.

Synergistic Effect of Rutile and Brookite TiO2 for Photocatalytic Formic Acid Dehydrogenation.

Solar energy is an ideal clean and inexhaustible energy source. Solar-driven formic acid (FA) dehydrogenation is one of the promising strategies to address safety and cost issues related to the storage, transport, and distribution of hydrogen energy. For FA dehydrogenation, the O-H and C-H cleavages are the key steps, and developing a photocatalyst with the ability to break these two bonds is critical. In this work, both density functional theory (DFT) calculation and experimental results confirmed the positive synergistic effect between brookite and rutile TiO2 for O-H and C-H cleavage in HCOOH. Further, brookite TiO2 is beneficial to the generation of the •OH radical and significantly promotes C-H cleavage in formate. Under optimized conditions, the H2 production efficiency of FA dehydrogenation can reach up to 30.4 µmol·mg-1·h-1, which is the highest value compared with similar reported TiO2-based systems and over 1.7 times the reported highest value of Au0.75Pd0.25/TiO2 photocatalysts. More importantly, after more than 42 days (>500 h) of irradiation, the system still demonstrated high H2 production activity, indicating the potential for practical application. This work provides a valuable strategy to improve both the efficiency and stability of photocatalytic FA dehydrogenation under mild conditions.

Capsaicin combined with stem cells improved mitochondrial dysfunction in PIG3V cells, an immortalized human vitiligo melanocyte cell line, by inhibiting the HSP70/TLR4/mTOR/FAK signaling axis.

BACKGROUND: Vitiligo is a common autoimmune skin disease. Capsaicin has been found to exert a positive effect on vitiligo treatment, and mesenchymal stem cells (MSCs) are also confirmed to be an ideal cell type. This study aimed to explore the influence of capsaicin combined with stem cells on the treatment of vitiligo and to confirm the molecular mechanism of capsaicin combined with stem cells in treating vitiligo. METHODS AND RESULTS: PIG3V cell proliferation and apoptosis were detected using CCK-8 and TUNEL assays, MitoSOX Red fluorescence staining was used to measure the mitochondrial ROS level, and JC-1 staining was used to detect the mitochondrial membrane potential. The expression of related genes and proteins was detected using RT‒qPCR and Western blotting. Coimmunoprecipitation was used to analyze the protein interactions between HSP70 and TLR4 or between TLR4 and mTOR. The results showed higher expression of HSP70 in PIG3V cells than in PIG1 cells. The overexpression of HSP70 reduced the proliferation of PIG3V cells, promoted apoptosis, and aggravated mitochondrial dysfunction and autophagy abnormalities. The expression of HSP70 could be inhibited by capsaicin combined with MSCs, which increased the levels of Tyr, Tyrp1 and DCT, promoted the proliferation of PIG3V cells, inhibited apoptosis, activated autophagy, and improved mitochondrial dysfunction. In addition, capsaicin combined with MSCs regulated the expression of TLR4 through HSP70 and subsequently affected the mTOR/FAK signaling pathway CONCLUSIONS: Capsaicin combined with MSCs inhibits TLR4 through HSP70, and the mTOR/FAK signaling pathway is inhibited to alleviate mitochondrial dysfunction and autophagy abnormalities in PIG3V cells.

Combination of 308-nm excimer laser and piperine promotes melanocyte proliferation, migration, and melanin content production via the miR-328/SFRP1 axis.

OBJECTIVE: Both piperine and a 308-nm excimer laser have significant curative effects on vitiligo. This study mainly explored the molecular mechanism of a 308-nm excimer combined with piperine in regulating melanocyte proliferation. METHODS: Epidermal melanocytes were cultured in piperine solution, and the cells were irradiated by an XTRAC excimer laser treatment system at 308-nm output monochromatic light. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were for detecting the expression levels of genes or proteins. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and Transwell method was for assessing cell viability and migration capacity. The content of melanin was also detected. RESULTS: The combination of the 308-nm excimer laser and piperine enhanced the cell proliferation, migration, and melanin production of melanocytes and upregulated the level of miR-328, and restraint of miR-328 reversed the influence of the 308-nm excimer laser and piperine. Secreted frizzled-related protein 1 (SFRP1) is a direct target gene of miR-328, and miR-328 can inhibit the expression of SFRP1 and elevate the protein level of the Wnt/ß-catenin signaling pathway. CONCLUSION: The 308-nm excimer laser combined with piperine may be more efficient than piperine alone in the remedy of vitiligo, and the miR-328/SFRP1 and Wnt/ß-catenin pathways are participated in the proliferation, migration, and melanin synthesis of melanocytes.

The effect of iron supplementation in preterm infants at different gestational ages.

BACKGROUND: Iron deficiency (ID) is the most prevalent nutritional deficiency disease in preterm infants, significantly affecting their growth and development. For preterm infants to flourish physically and neurologically, timely iron supplementation is essential. The main goals of this study were to determine whether the present iron supplementation regimen results in iron overload in late preterm infants and whether it can meet the growth requirements of early preterm infants for catch-up. METHODS: We conducted a prospective follow-up study on preterm infants at the Department of Child Health, West China Second University Hospital, Sichuan University, from January 1, 2020, to August 31, 2020. In this study, 177 preterm infants were divided into two groups based on gestational age-early preterm infants (gestational age < 34 weeks) and late preterm infants (gestational age ≥ 34 weeks and < 37 weeks)-to compare the incidence of iron deficiency, iron status, and physical growth of preterm infants receiving iron supplements (2-4 mg/kg/d). RESULTS: Iron supplementation considerably reduced the incidence of iron deficiency in preterm infants. The prevalence of iron deficiency in early preterm infants and late preterm infants was 11.3% and 5.1%, respectively, at the corrected gestational age of 3 months; at the corrected gestational age of 6 months, the prevalence was 5.3% and 6.3%, respectively. No preterm infants with iron deficiency were detected in either group at the corrected gestational age of 12 months. Ferritin was substantially lower in early preterm infants (36.87 ± 31.57 ng/ml) than in late preterm infants (65.78 ± 75.76 ng/ml) at the corrected gestational age of 3 months (p < 0.05). A multifactorial regression analysis of factors influencing iron metabolism levels in preterm infants revealed a positive relationship between log10hepcidin, birth weight, and ferritin, with higher birth weights resulting in higher ferritin levels. CONCLUSIONS: Postnatal iron supplementation at 2-4 mg/kg/d in preterm infants significantly decreases the incidence of ID. There were substantial differences in iron levels across preterm infants of varying gestational ages. A tailored iron supplementation plan based on growth, birth weight, and gestational age may be a more suitable route for iron supplementation. Although the current study found that the postnatal iron status of early preterm infants differed from that of late preterm infants, the actual mechanism of action remains unknown, and large-sample, multicenter clinical studies are required to investigate this further.

TRPV1-Lineage Somatosensory Fibers Communicate with Taste Neurons in the Mouse Parabrachial Nucleus.

Trigeminal neurons convey somatosensory information from craniofacial tissues. In mouse brain, ascending projections from medullary trigeminal neurons arrive at taste neurons in the parabrachial (PB) nucleus, suggesting that taste neurons participate in somatosensory processing. However, the cell types that support this convergence were undefined. Using Cre-directed optogenetics and in vivo neurophysiology in anesthetized mice of both sexes, here we studied whether transient receptor potential vanilloid 1 (TRPV1)-lineage nociceptive and thermosensory fibers are primary neurons that drive trigeminal circuits reaching PB taste cells. We monitored spiking activity in individual PB neurons during photoexcitation of the terminals of TRPV1-lineage fibers arriving at the dorsal trigeminal nucleus caudalis, which relays orofacial somatosensory messages to the PB area. We also recorded PB neural responses to oral delivery of taste, chemesthetic, and thermal stimuli. We found that optical excitation of TRPV1-lineage fibers elicited responses in traditionally defined taste neurons in lateral PB nuclei. The tuning of neurons across diverse tastes associated with their sensitivity to TRPV1-lineage fiber stimulation, which only sparingly engaged neurons oriented to preferred tastes like sucrose. Moreover, neurons responsive to photostimulation of TRPV1-lineage afferents showed strong responses to temperature including noxious heat, which predominantly excited PB bitter taste cells. Multivariate and machine learning analyses revealed the PB confluence of TRPV1-lineage signals with taste captured sensory valence information shared across aversive gustatory, nociceptive, and thermal stimuli. Our results reveal that TRPV1-lineage fibers, which have defined roles in thermosensation and pain, communicate with PB taste neurons. This multisensory convergence supports dependencies between gustatory and somatosensory hedonic representations in the brain.SIGNIFICANCE STATEMENT The parabrachial (PB) nucleus participates in autonomic and integrative neural processing for diverse sensory modalities. We recently found in mice that trigeminal neurons supplying craniofacial somatosensation project to PB neurons sensitive to tastes. Here, we show that trigeminal projections to PB gustatory cells are driven by a genetic class of thermosensory and nociceptive fiber. Input from these fibers was associated with PB neural sensitivity to aversive oral temperatures and tastes and supported a multimodal neural representation of sensory valence across gustatory, nociceptive, and thermal stimuli. These results reveal gustation and somatosensation to be only components of a larger PB code that captures sensory value. Defining this circuit has implications for understanding the neural representation of taste, temperature, and also pain-related phenomena.

2,5-Dihydroxyterephthalic Acid: A Matrix for Improved Detection and Imaging of Amino Acids.

Amino acids (AAs), which are low-molecular-weight (low-MW) metabolites, serve as essential building blocks not only for protein synthesis but also for maintaining the nitrogen balance in living systems. In situ detection and imaging of AAs are crucial for understanding more complex biological processes. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is a label-free mass spectrometric imaging technique that enables the simultaneous detection and imaging of the spatial distribution and relative abundance of different endogenous/exogenous compounds in biological samples. The excellent efficiency of MALDI-MSI is attributed to the choice of the MALDI matrix. However, to the best of our knowledge, no matrix has been specifically developed for AAs. Herein, we report a MALDI matrix, 2,5-dihydroxyterephthalic acid (DHT), which can improve the detection and imaging of AAs in biological samples by MALDI-MS. Our results indicated that DHT exhibited strong ultraviolet-visible (UV-vis) absorption, uniform matrix deposition, and high vacuum stability. Moreover, the matrix-related ion signals produced from DHT were reduced by 50 and 71.8% at m/z < 500 compared to the commonly used matrices of 2,5-dihydroxybenzoic acid (DHB) and α-cyano-4-hydroxycinnamic acid (CHCA), respectively, in their respective organic solvents. In terms of quantitative performance, arginine, glutamic acid, glutamine, and proline can be detected with limits of detection of 6, 4, 6, and 4 ng/mL, respectively, using the DHT as the matrix. Using DHT as the matrix, all 20 protein AAs were successfully detected in human serum by MALDI-MS, whereas only 7 and 10 AAs were detected when DHB and CHCA matrices were used, respectively. Furthermore, 20 protein AAs and taurine were successfully detected and imaged in a section of edible Crassostrea gigas (oyster) tissue for the first time. Our study demonstrates that using DHT as a matrix can improve the detection and imaging of AAs in biological samples by MALDI-MS.

High-throughput MALDI-MSI metabolite analysis of plant tissue microarrays.

A novel metabolomics analysis technique, termed matrix-assisted laser desorption/ionization mass spectrometry imaging-based plant tissue microarray (MALDI-MSI-PTMA), was successfully developed for high-throughput metabolite detection and imaging from plant tissues. This technique completely overcomes the disadvantage that metabolites cannot be accessible on an intact plant tissue due to the limitations of the special structures of plant cells (e.g. epicuticular wax, cuticle and cell wall) through homogenization of plant tissues, preparation of PTMA moulds and matrix spraying of PTMA sections. Our study shows several properties of MALDI-MSI-PTMA, including no need of sample separation and enrichment, high-throughput metabolite detection and imaging (>1000 samples per day), high-stability mass spectrometry data acquisition and imaging reconstruction and high reproducibility of data. This novel technique was successfully used to quickly evaluate the effects of two plant growth regulator treatments (i.e. 6-benzylaminopurine and N-phenyl-N'-1,2,3-thiadiazol-5-ylurea) on endogenous metabolite expression in plant tissue culture specimens of Dracocephalum rupestre Hance (D. rupestre). Intra-day and inter-day evaluations indicated that the metabolite data detected on PTMA sections had good reproducibility and stability. A total of 312 metabolite ion signals in leaves tissues of D. rupestre were detected, of which 228 metabolite ion signals were identified, they were composed of 122 primary metabolites, 90 secondary metabolites and 16 identified metabolites of unknown classification. The results demonstrated the advantages of MALDI-MSI-PTMA technique for enhancing the overall detection ability of metabolites in plant tissues, indicating that MALDI-MSI-PTMA has the potential to become a powerful routine practice for high-throughput metabolite study in plant science.

A concentration-descending washing strategy with methanol for the enhancement of protein imaging in biological tissues by MALDI-MS.

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is a powerful approach that has been widely used for in situ detection of various endogenous compounds in tissues. However, there are still challenges with in situ analysis of proteins using MALDI-MSI due to the ion suppression effects of small molecules in tissue sections. Therefore, tissue-washing steps are crucial for protein MALDI tissue imaging to remove these interfering molecules. Here, we successfully developed a new method named the concentration-descending washing strategy (CDWS) with methanol (MeOH), i.e., washing of biological tissue with 100%, 95%, and 70% MeOH solutions, for the enhancement of endogenous in situ protein detection and imaging in tissues using MALDI-MS. The method of MeOH-based CDWS (MeOH-CDWS) led to the successful in situ detection of 272 ± 3, 185 ± 4, and 134 ± 2 protein ion signals from rat liver, rat brain, and germinating Chinese-yew seed tissue sections, respectively. By comparison, 161 ± 2, 121 ± 1, and 114 ± 2 protein ions were detected by three commonly used methods, i.e., Carnoy's wash, ethanol (EtOH)-based CAWS (i.e., concentration-ascending washing strategy, 70% EtOH followed by 90% EtOH/9% AcOH), and isopropanol (iPrOH)-based CAWS (70% iPrOH followed by 95% iPrOH), respectively, in rat liver tissue sections, indicating that 68.9 ± 3.1%, 124.8 ± 3.3%, and 138.6 ± 4.4% more protein ion signals could be detected by the use of MeOH-CDWS than the three abovementioned washing strategies. Our results show that the use of MeOH-CDWS improves the performance of MALDI-MSI for in situ protein detection such as the number and intensity of proteins. The use of MeOH-CDWS improves the fixation of proteins and thus reduces the loss of proteins, which significantly reduces protein delocalization in tissue and enhances the performance of MALDI tissue imaging of protein. Thus, the use of MeOH-CDWS improves the quality of protein images in tissue sections through MALDI-MSI and has the potential to be used as standard practice for MALDI tissue imaging of proteins.

Failure to diagnose hypochondroplasia by prenatal diagnosis: a case report.

BACKGROUND: Hypochondroplasia (HCH) is a common nonlethal skeletal dysplasia caused by pathogenic variations in the fibroblast growth factor receptor 3 (FGFR3) gene, and HCH has similar clinical manifestations with achondroplasia (ACH), which can be screened during the fetal period by prenatal ultrasound testing and diagnosed by genetic testing. CASE PRESENTATION: we report the special case of a patient with obvious growth retardation and rhizomelic disproportionate short stature, accompanied by other manifestations, including an enlarged head and short hands at 1 year old. However, several multiple color ultrasound exams identified shortened limbs (< 3rd percentile), an increased biparietal diameter (> 95th percentile) and a low nasal bridge in the fetal period. Due to the high incidence rate of ACH, genetic testing for the hotspot FGFR3 gene c.1138 g > A pathogenic variations was performed immediately in the third trimester. Unfortunately, the definitive diagnosis could not be made before birth due to the negative result of hotspot gene exam. Whole exome sequencing (WES) was performed at 1 year identified FGFR3 gene c.1620C > A variations positivity, and the patient was finally diagnosed as HCH. CONCLUSION: Our report extends the understanding of the limitations of prenatal genetic diagnostic testing, especially the hot spot pathogenic variations test should be not the only clinical diagnostic basis. Moreover, this case also emphasizes that further gene analysis for patients with significant conflict between the clinical manifestation and the prenatal genetic panel examination findings should be reconducted timely to spare the family from a delayed diagnosis or a misdiagnosis.

Biological interactions of polystyrene nanoplastics: Their cytotoxic and immunotoxic effects on the hepatic and enteric systems.

As emerging pollutants in the environment, nanoplastics (NPs) can cross biological barriers and be enriched in organisms, posing a greatest threat to the health of livestock and humans. However, the size-dependent toxic effects of NPs in higher mammals remain largely unknown. To determine the size-dependent potential toxicities of NPs, we exposed mouse (AML-12) and human (L02) liver cell lines in vitro, and 6-week-old C57BL/6 mice (well-known preclinical model) in vivo to five different sizes of polystyrene NPs (PS-NPs) (20, 50, 100, 200 and 500 nm). We found that ultra-small NPs (20 nm) induced the highest cytotoxicity in mouse and human liver cell lines, causing oxidative stress and mitochondrial membrane potential loss on AML-12 cells. Unexpectedly in vivo, after long-term oral exposure to PS-NPs (75 mg/kg), medium NPs (200 nm) and large NPs (500 nm) induced significant hepatotoxicity, evidenced by increased oxidative stress, liver dysfunction, and lipid metabolism disorders. Most importantly, medium or large NPs generated local immunotoxic effects via recruiting and activating more numbers of neutrophils and monocytes in the liver or intestine, which potentially resulted in increased proinflammatory cytokine secretion and the tissue damage. The discrepancy in in vitro-in vivo toxic results might be attributed to the different properties of biodistribution and tissue accumulation of different sized NPs in vivo. Our study provides new insights regarding the hepatotoxicity and immunotoxicity of NPs on human and livestock health, warranting us to take immense measures to prevent these NPs-associated health damage.

Sinomenine improves renal fibrosis by regulating mesenchymal stem cell-derived exosomes and affecting autophagy levels.

BACKGROUND: This study attempts to investigate the therapeutic effect of sinomenine on renal fibrosis and its mechanism. METHODS: The 8-week-old C57BL/6 male mice were randomly divided into sham group, UUO model group, UUO sinomenine group (UUO + Sino 50), UUO + sinomenine group (UUO + Sino 100), UUO + exosome group (exo), and UUO + exo-inhibitor. The pathological changes of kidney were observed by H&E staining, the degree of renal interstitial fibrosis was detected by MASSON and Sirius red staining, and the expressions of fibrosis and autophagy markers were detected by real-time fluorescence quantitative PCR and WB. NTA and electron microscopy were used to analyze exo secretion after sinomenine treatment. RESULTS: Sinomenine could improve the progression of renal fibrosis without causing tissue damage including heart, lungs and liver. Sinomenine could promote autophagosome formation. It could promote the secretion of exosomes from bone marrow mesenchymal stem cells (BMSCs). Sinomine regulates the PI3K-AKT pathway through BMSC-exo carrying miR-204-5p, affecting autophagy level and alleviating the process of renal fibrosis. CONCLUSION: Our study suggests that sinomine could improve the progression of renal fibrosis by influencing the expression of miR-204-5p in BMSC-exo and regulating the PI3K-AKT pathway.

Efficacy analysis of multidisciplinary treatment for Wilms tumor in a single center.

OBJECTIVE: To analyze the efficacy of multidisciplinary treatment for Wilms tumor (WT) in Kunming Children's Hospital, and investigate the risk factors affecting the prognosis of WT. METHODS: The clinic-pathological data were collected and analyzed in patients with unilateral WT treated in Kunming Children's Hospital from January 2017 to July 2021. Research subjects were selected according to inclusion criteria and exclusion criteria. The risk factors and independent risk factors that affect the prognosis of patients with WT were determined by Kaplan-Meier survival analysis and Cox proportional hazards model, respectively. OUTCOME: A total of 68 children were included in this study, and the 5-year overall survival (OS) rate was 87.4%. Kaplan-Meier survival analysis results showed that ethnicity (P = 0.020), the tumor volume of resection (P = 0.001), histological type (P < 0.001), and postoperative recurrence (P < 0.001) were the risk factors affecting the prognosis of children with WT. The results of the Cox proportional hazards model showed that only the histological type (P = 0.018) was the independent risk factor for the prognosis of WT. CONCLUSION: The efficacy of multidisciplinary treatment for WT was satisfying. The histological type has important predictive value for the prognosis of WT, and the patient with unfavorable histology has a poor prognosis.

Adaptive Reflection Detection and Control Strategy of Pointer Meters Based on YOLOv5s.

Reflective phenomena often occur in the detecting process of pointer meters by inspection robots in complex environments, which can cause the failure of pointer meter readings. In this paper, an improved k-means clustering method for adaptive detection of pointer meter reflective areas and a robot pose control strategy to remove reflective areas are proposed based on deep learning. It mainly includes three steps: (1) YOLOv5s (You Only Look Once v5-small) deep learning network is used for real-time detection of pointer meters. The detected reflective pointer meters are preprocessed by using a perspective transformation. Then, the detection results and deep learning algorithm are combined with the perspective transformation. (2) Based on YUV (luminance-bandwidth-chrominance) color spatial information of collected pointer meter images, the fitting curve of the brightness component histogram and its peak and valley information is obtained. Then, the k-means algorithm is improved based on this information to adaptively determine its optimal clustering number and its initial clustering center. In addition, the reflection detection of pointer meter images is carried out based on the improved k-means clustering algorithm. (3) The robot pose control strategy, including its moving direction and distance, can be determined to eliminate the reflective areas. Finally, an inspection robot detection platform is built for experimental study on the performance of the proposed detection method. Experimental results show that the proposed method not only has good detection accuracy that achieves 0.809 but also has the shortest detection time, which is only 0.6392 s compared with other methods available in the literature. The main contribution of this paper is to provide a theoretical and technical reference to avoid circumferential reflection for inspection robots. It can adaptively and accurately detect reflective areas of pointer meters and can quickly remove them by controlling the movement of inspection robots. The proposed detection method has the potential application to realize real-time reflection detection and recognition of pointer meters for inspection robots in complex environments.

Effect of mitomycin C and 5-fluorouracil on wound healing in patients undergoing glaucoma surgery: A meta-analysis.

Increased intraocular pressure (IOP) is a risk factor for glaucoma. One treatment option is trabeculectomy. Antimetabolic agents are used in the operation to decrease the post-operative scarring of the wound. The two most common medicines are Mitomycin C (MMC) and 5-Fluorouracil (5-FU). The aim of this research is to assess the effect of MMC on post-operation wound healing in comparison with 5-FU in addition to trabeculectomy. Well, we went through four common databases. Our language was limited to English during the study. The last time we looked at the e-databases was August 2023. Case control studies were performed where MMC resulted in better wound healing than 5-FU. Researchers selected a total of 1023 trials and eventually selected six trials for data analysis. Four hundred and ninety one cases of glaucoma were treated with trabeculectomy. Among them, 246 were given MMC and 245 were given 5-FU during operation. Six trials showed that there was no statistical difference between MMC and 5-FU in the incidence of post-operative wound leak in glaucoma patients who received trabeculectomy (OR, 1.21; 95% CI, 0.63-2.30 p = 0.57); Five trials demonstrated that MMC was associated with a reduced risk of post-operative corneal damage compared to 5-FU injection (OR, 0.18; 95% CI, 0.06-0.56 p = 0.003); In both trials, the incidence of post-operative bleeding was not significantly different from that of 5-FU injected in the MMC group (OR, 0.33; 95% CI, 0.05-2.16 p = 0.25). Our results indicate that MMC is superior to 5-FU in the reduction of post-operative corneal injury. Additional comparisons between MMC and 5-FU are required in order to increase the reliability and effectiveness of these findings.

Taming of Singlet Oxygen: Towards Artificial Oxygen Carriers Based on 1,4-Dialkylnaphthalenes.

Naphthalene endoperoxides are known as convenient sources of singlet oxygen (O2 , 1 Δg ), which is the major product of endoperoxide cycloreversion reaction. However, their potential as carriers of ground-state molecular oxygen (O2 , 3 Σg ) similar to artificial oxygen carriers remains largely unexplored. This is due to the extreme reactivity and cytotoxic effects of the released singlet oxygen. We now report that a compound with a bimodular design, which incorporates an endoperoxide and an efficient physical quencher of singlet oxygen, 1,4-diazabicyclo[2.2.2]octane (DABCO), produces exclusively ground-state molecular oxygen. This result, coupled with the fact that oxygen release rates from endoperoxides are highly amenable to fine-tuning in a very broad range, and open to targeting by ligand attachment, raises the potential of these compounds far above any comparable chemical, or even biochemical sources. In cell culture experiments, we showed that the addition of the endoperoxide-quencher conjugate can enhance and sustain cell proliferation.

Decreased taste sensitivity to sucrose in dopamine D3 receptor mutant mice.

Dopamine plays a key role in food rewards and sweet-taste stimulation. We examined the basis for behavioral responses to sweet taste in dopamine D3 receptor-deficient (D3-/-) mice by determining whether the absence of D3 receptors affects the sensitivity to dilute sucrose solutions. In experiment 1, we measured the intensity generalization threshold of conditioned taste aversion (CTA) to a 0.2 M sucrose solution. Results showed that the generalization thresholds were 0.025-0.05 M in D3-/- mice and 0.0025-0.005 M in wild-type (WT) mice. In experiment 2, we found that D3-/- and WT mice had similar capabilities to form and extinguish CTAs. Since the intensity generalization threshold is mainly due to a combination of sweet-taste sensitivity and the robust nature of CTA formation, the results showed that taste sensitivity to sucrose in D3-/- mice was lower than that in WT mice. In experiment 3, to test whether the peripheral sensory signaling may also be affected by the disruption of the dopamine D3 receptors, the mRNA expression levels of sweet-taste-related proteins in taste buds of D3-/- mice were determined. The T1R1 and BDNF mRNA expression levels in D3-/- mice were higher than the controls, whereas T1R2, T1R3, α-gustducin, and TRPM5 mRNA were similar. These findings suggest that disruption of dopamine D3 receptor-mediated signaling decreases the sweet-taste sensitivity and alters the mRNA expression levels of some taste-related molecules.

Breeding a Soybean Cultivar Heinong 531 with Peking-Type Cyst Nematode Resistance, Enhanced Yield, and High Seed-Oil Contents.

Soybean cyst nematode (SCN) is a destructive threat to soybean production. It is economically important to develop a new SCN-resistant soybean cultivar with high yield and other good agronomic traits. In this study, a yellow-seed-coated and yellow-hilum-pigmented cultivar Heinong 531 belonging to maturity group I was developed by a pedigree breeding method through a test-cross between a female parental SCN-resistant soybean cultivar Pengdou 158 and a male parental line F1 (high-yield but SCN-susceptible Hefeng 55 × SCN-resistant Kangxian 12). Heinong 531 was evaluated for SCN resistance in both SCN-infested field and autoclaved soil inoculated with hatched second-stage juveniles of SCN HG Type 0. The results indicated that SCN development at all stages in Heinong 531 was suppressed and the female index was only 1.6 to 5.6%. Heinong 531 as well as Pengdou 158 and Kangxian 12 were identified as carrying the Peking-type resistance with both rhg1-a GmSNAP18 and Rhg4 GmSHMT08 genes. In the 2-year regional trials, the average yield of Heinong 531 reached 2805.0 kg/ha, and the 1-year production trial demonstrated an average yield of 2,751.5 kg/ha with yield increase of >12.0% when compared with the local cultivars. The average seed-fat (oil) contents of Heinong 531 reached up to 22.3%. The Peking-type SCN-resistant Heilong 531 with enhanced yield and high seed-oil contents was released in China in June 2021 with the certified number of 'Heishendou 20210004'. These agronomic traits make Heinong 531 a good prospect in a wide attempt to control SCN in the main soybean-producing areas of Northeast China.