Identifying Potential Diagnostic and Therapeutic Targets for Infantile Hemangioma Using WGCNA and Machine Learning Algorithms.

Infantile hemangioma (IH) is the most common benign vascular tumor during infancy and childhood and is characterized by abnormal vascular development. It is the most common vascular tumor and its related mechanisms and treatments remain a problem. IH-related biomarkers have been identified using transcriptome analysis and can be used to predict clinical outcomes. This study aimed to identify the key target genes for IH treatment and explore their possible roles in the IH pathophysiology. Gene records were acquired from the Gene Expression Omnibus database. Utilizing integrated weighted gene co-expression network examination, gene clusters were determined. Single-sample gene set enrichment analysis was performed to gauge immune infiltration. Essential genes were identified via Random Forest and Least Absolute Selection and Shrinkage Operator analyses. Ultimately, a set of five pivotal genes associated with the ailment was identified (NETO2, IDO1, KDR, MEG3, and TMSB15A). A nomogram for predicting IH diagnosis was constructed based on hub genes. The calibration curve showed valid agreement between the prediction and conclusion that the key genes in the model were clinically significant. Neuropilin and Tolloid-like 2 (NETO2) are closely associated with tumor development. The role value of NETO2 expression levels increased in hemangioma-derived endothelial cells (HemECs). After silencing NETO2, the growth and migration of cancer cells were significantly restrained. This study revealed the critical role of NETO2 in IH development, suggesting that targeting NETO2 may be effective in improving the therapeutic outcome of IH.

Comprehensive evaluation of Chinese herbal compound prescriptions for postoperative spinal cord injury: A network meta-analysis of randomized controlled trials.

Background: Spinal cord injury (SCI) is a catastrophic condition associated with spinal nerve damage, which can lead to complete or partial loss of sensory and motor functions. Chinese herbal compound prescriptions (CHCP) have shown varying degrees of therapeutic effects on spinal cord injuries. However, there is a significant lack of clinical evidence-based research to substantiate these effects. Purpose: This study aims to thoroughly assess the viability of CHCPs in postoperative SCI through network meta-analysis. Methods: Computer searches were conducted across multiple databases, including PubMed, Cochrane Library, Embase, Web of Science, CNKI, Wanfang, VIP, and CBM, from their inception until May 2024. The meta-analysis adhered to the PRISMA guidelines and was registered in the PROSPERO database (CRD42023462686). A network meta-analysis was performed using the BUGSnet software package via R. Study design: A network meta-analysis of randomized clinical trials (RCTs). Results: A total of 26 RCTs involving 1848 patients were ultimately included. The network meta-analysis revealed the effectiveness in improving ASIA motor score as follows: "HQGZD" > "Other Decoctions" > "BYHWD" > "TDHXD" > "THCQD" > "Surgery". For ASIA sensory score, the effectiveness ranking was: "HQGZD" > "Other Decoctions" > "BYHWD" > "TDHXD" > "THCQD" > "Surgery". Additionally, the experimental group had a higher ADL score compared to the control group, with a statistically difference [SMD = 1.08, 95 % CI = (0.88, 1.27), p < 0.05]. The experimental group had fewer adverse events compared to the control group, with a statistically difference [RR = 0.41, 95 % CI (0.22, 0.78), p < 0.05]. Conclusion: The findings suggest that CHCP can mprove postoperative ASIA motor and sensory scores, enhance ADL scores, and reduce adverse events following SCI surgery. Specifically, combining surgery with Huangqi Guizhi Wuwu Decoction or Buyang Huanwu Decoction may provide superior therapeutic effects in SCI treatment. Integrating CHCP into postoperative care for SCI patients may offer potential benefits.

[Pharmacovigilance guidelines for clinical application of oral Chinese patent medicines].

Oral Chinese patent medicine is the essence of effective prescriptions created and summarized by Chinese medical scientists through thousands of years of medical practice. It is portable and convenient, with an obvious curative effect and other characteristics. However, at present, oral Chinese patent medicine is rich in dosage forms, various in types, complex in mechanism of action, and broad in clinical positioning. In clinical application, there are often cases of drug use without reference to instructions,repeated drug use, and prolonged drug use, which highlights safety problems such as adverse reactions and hepatorenal toxicity. Oral Chinese patent medicine pharmacovigilance is facing challenges. World Health Organization(WHO) has issued the WHO guidelines on safety monitoring of herbal medicines in pharmacovigilance systems, and International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use(ICH) has issued the ICH E2 pharmacovigilance guidelines. The United States has issued the Pharmacovigilance management standards and pharmacoepidemiological assessment guidelines, and the European Union has issued the Guidelines on good pharmacovigilance practices. Japan, South Korea, and other countries in the Asia Pacific region have established their own pharmacovigilance systems, but currently, there are no pharmacovigilance guidelines related to oral Chinese patent medicine in China. Therefore, experts from many disciplines and fields in China were invited to jointly develop the Pharmacovigilance guidelines for clinical application of oral Chinese patent medicines, which aims to develop pharmacovigilance guidelines for clinical application that are consistent with China's national conditions and highlight the characteristics of oral Chinese patent medicine, and provide guidance for clinically safe and rational drug application in medical institutions.

Comparative analysis of new mScarlet-based red fluorescent tags in Caenorhabditis elegans.

One problem that has hampered the use of red fluorescent proteins in the fast-developing nematode Caenorhabditis elegans has been the substantial time delay in maturation of several generations of red fluorophores. The recently described mScarlet-I3 protein has properties that may overcome this limitation. We compare here the brightness and onset of expression of CRISPR/Cas9 genome-engineered mScarlet, mScarlet3, mScarlet-I3, and GFP reporter knock-ins. Comparing the onset and brightness of expression of reporter alleles of C. elegans golg-4, encoding a broadly expressed Golgi resident protein, we found that the onset of detection of mScarlet-I3 in the embryo is several hours earlier than older versions of mScarlet and comparable to GFP. These findings were further supported by comparing mScarlet-I3 and GFP reporter alleles for pks-1, a gene expressed in the CAN neuron and cells of the alimentary system, as well as reporter alleles for the pan-neuronal, nuclear marker unc-75. Hence, the relative properties of mScarlet-I3 and GFP do not depend on cellular or subcellular context. In all cases, mScarlet-I3 reporters also show improved signal-to-noise ratio compared to GFP.

Oxysulfonylation of Alkynes with Sodium Sulfinates to Access ß-Keto Sulfones Catalyzed by BF3·OEt2.

An efficient and operationally simple method for the synthesis of ß-keto sulfones through the BF3·OEt2-promoted reaction of alkynes and sodium sulfinates is developed. With its facile and selective access to the targets, it features good functional group compatibility, mild conditions, easily available starting materials, and good yields. Notably, the reaction does not require metal catalysts or chemical reagents with pungent odors.

Circulating inflammatory cytokines and the risk of sepsis: a bidirectional mendelian randomization analysis.

BACKGROUND: Sepsis is a life-threatening condition that is characterized by multiorgan dysfunction and caused by dysregulated cytokine networks, which are closely associated with sepsis progression and outcomes. However, currently available treatment strategies that target cytokines have failed. Thus, this study aimed to investigate the interplay between genetically predicted circulating concentrations of cytokines and the outcomes of sepsis and to identify potential targets for sepsis treatment. METHODS: Data related to 35 circulating cytokines in 31,112 individuals (including 11,643 patients with sepsis) were included in genome-wide association studies (GWASs) from the UK Biobank and FinnGen consortia. A bidirectional two-sample Mendelian randomization (MR) analysis was performed using single nucleotide polymorphisms (SNPs) to evaluate the causal effects of circulating cytokines on sepsis outcomes and other cytokines. RESULTS: A total of 35 inflammatory cytokine genes were identified in the GWASs, and 11 cytokines, including Interleukin-1 receptor antagonist (IL-1ra), macrophage inflammatory protein 1 (MIP1α), IL-16, et al., were associated with sepsis outcome pairs according to the selection criteria of the cis-pQTL instrument. Multiple MR methods verified that genetically predicted high circulating levels of IL-1ra or MIP1α were negatively correlated with genetic susceptibility to risk of sepsis, including sepsis (28-day mortality), septicaemia, streptococcal and pneumonia-derived septicaemia (P ≤ 0.01). Furthermore, genetic susceptibility of sepsis outcomes except sepsis (28-day mortality) markedly associated with the circulating levels of five cytokines, including active plasminogen activator inhibitor (PAI), interleukin 7 (IL-7), tumour necrosis factor alpha (TNF-α), beta nerve growth factor (NGF-ß), hepatic growth factor (HGF) (P < 0.05). Finally, we observed that the causal interaction network between MIP1α or IL-1ra and other cytokines (P < 0.05). CONCLUSIONS: This comprehensive MR analysis provides insights into the potential causal mechanisms that link key cytokines, particularly MIP1α, with risk of sepsis, and the findings suggest that targeting MIP1α may be a potential strategy for preventing sepsis.

[Analysis of risk factors for postoperative delirium in elderly patients undergoing spinal surgery].

OBJECTIVE: To investigate the risk factors of postoperative delirium in elderly patients undergoing spine surgery. METHODS: The basic case data of 566 patients who underwent spine surgery under general anesthesia from January 2021 to January 2023 were retrospectively analyzed. There were 296 males and 270 females with an average age of (71.58 ± 4.21) years old. There were 195 cases of cervical spine surgery, 26 cases of thoracic spine surgery and 345 cases of lumbar spine surgery.According to the occurrence of postoperative delirium, the patients were divided into postoperative delirium group(41 patients) and non-delirium group (525 patients). Univariate analysis was used to analyze the possible influencing factors such as gender, age, weight, smoking history, drinking history, surgical site, preoperative anxiety, intraoperative hypotension times, blood loss and so on, and binary Logistic regression was used to analyze the univariate factors with P<0.05. RESULTS: A total of 41 patients developed postoperative delirium. Univariate analysis showed that age (P=0.000), duration of surgery (P=0.039), preoperative anxiety (P=0.001), blood loss (P=0.000), history of opioid use (P=0.003), history of stroke (P=0.005), C-reactive protein (P=0.000), sodium ion(P=0.000) were significantly different between delirium group and non-delirium group. These factors were included in the binary Logistic regression analysis, and the results showed that age [OR=0.729, 95%CI(0.569, 0.932), P=0.012], opioid use [OR=21.500, 95%CI(1.334, 346.508), P=0.031], blood loss [OR=0.932, 95%CI(0.875, 0.993), P=0.029], C-reactive protein [OR=0.657, 95%CI(0.485, 0.890), P=0.007], preoperative anxiety [OR=23.143, 95%CI(1.859, 288.090), P=0.015], and sodium [OR=1.228, 95%CI(1.032, 1.461), P=0.020] were independent risk factors for the development of delirium after spinal surgery in elderly patients. CONCLUSION: Age, opioid use, blood loss, preoperative anxiety, elevated c-reactive protein, and hyponatremia are independent risk factors for the development of postoperative delirium in elderly patients undergoing spinal surgery.

Association of serum interleukin-6 with negative symptoms in stable early-onset schizophrenia.

BACKGROUND: Accumulating evidence suggests that the inflammatory cytokine interleukin-6 (IL-6) contributes to the pathophysiology of psychiatric disorders. However, there was no study concerning the relationship between IL-6 concentrations and clinical features in the chronic phase of early-onset schizophrenia (EOS). AIM: To investigate the relationship between serum IL-6 concentration and the clinical features of EOS. METHODS: We measured serum IL-6 Levels from 74 patients with chronic schizophrenia, including 33 with age at onset < 21 years (EOS group) and 41 with onset ≥ 21 years in [adult-onset schizophrenia (AOS) group], and from 41 healthy controls. Symptom severities were evaluated using the Positive and Negative Syndrome Scale (PANSS). RESULTS: Serum IL-6 concentrations were higher in both EOS and AOS groups than healthy controls (F = 22.32, P < 0.01), but did not differ significantly between EOS and AOS groups (P > 0.05) after controlling for age, body mass index, and other covariates. Negative symptom scores were higher in the EOS group than the AOS group (F = 6.199, P = 0.015). Serum IL-6 concentrations in the EOS group were negatively correlated with both total PANSS-negative symptom score (r = -0.389, P = 0.032) and avolition/asociality subscore (r = -0.387, P = 0.026). CONCLUSION: Patients with EOS may have more severe negative symptoms than those with adult-onset schizophrenia during the chronic phase of the illness. IL-6 signaling may regulate negative symptoms and its avolition/asociality subsymptoms among the early-onset chronic schizophrenic patients.

Exploring the ecological security evaluation of water resources in the Yangtze River Basin under the background of ecological sustainable development.

The Yangtze River (hereafter referred to as the YZR), the largest river in China, is of paramount importance for ensuring water resource security. The Yangtze River Basin (hereafter referred to as the YRB) is one of the most densely populated areas in China, and complex human activities have a significant impact on the ecological security of water resources. Therefore, this paper employs theories related to ecological population evolution and the Driving Force-Pressure-State-Impact-Response (DPSIR) model to construct an indicator system for the ecological security of water resources in the YRB. The report evaluates the ecological security status of water resources in each province of the YRB from 2010 to 2019, clarifies the development trend of its water resource ecological security, and proposes corresponding strategies for regional ecological security and coordinated economic development. According to the results of the ecological population evolution competition model, the overall indicator of the ecological security of water resources in the YRB continues to improve, with the safety level increasing annually. Maintaining sound management of water resources in the YRB is crucial for sustainable socioeconomic development. To further promote the ecological security of water resources in the YRB and the coordinated development of the regional economy, this paper proposes policy suggestions such as promoting the continuous advancement of sustainable development projects, actively adjusting industrial structure, continuously enhancing public environmental awareness, and actively participating in international ecological construction and seeking cooperation among multiple departments.

The mechanosensitive Piezo1 channel exacerbates myocardial ischaemia/reperfusion injury by activating caspase-8-mediated PANoptosis.

PANoptosis is a newly discovered type of cell death characterized by pyroptosis, apoptosis and/or necroptosis and has been implicated in the inflammatory response. Piezo1 is a mechanosensitive ion channel that plays important roles in physiological development and various diseases. However, whether cardiomyocytes undergo PANoptosis during myocardial ischaemia/reperfusion (I/R) injury and the role of Piezo1 in this process remain largely unexplored. In this study, our results revealed that the expression levels of the main components of the PANoptosome, including caspase-8, caspase-3, NLRP3, caspase-1, GSDMD, RIPK1, RIPK3 and MLKL, were significantly upregulated in I/R heart tissues over time, indicating the occurrence of PANoptosis in I/R hearts. Accordingly, Piezo1 expression was significantly upregulated in I/R-injured hearts and hypoxia/reoxygenation (H/R)-treated cardiomyocytes. In contrast, pharmacological inhibition of Piezo1 by the inhibitor GsMTx4 in mice markedly attenuated the I/R-mediated decline in cardiac contractile function and increases in infarct size, apoptosis, oxidative stress and inflammation accompanied by the inhibition of PANoptosis-related mediators in I/R hearts. Consistently, the effects of Piezo1 on calcium influx and PANoptosis were further verified by GsMTx4 and Piezo1 activator Yoda1 in H/R-treated cardiomyocytes in vitro. Moreover, caspase-8 rather than calcium influx was required for H/R-induced PANoptosis in vitro. Mechanistically, Piezo1 interacts with caspase-8, a key initial activator of the PANoptosome complex, which subsequently activates cardiomyocyte PANoptosis, leading to cardiac dysfunction. In summary, these data suggest that Piezo1 is a new cardiac mechanosensor that promotes cardiac I/R injury possibly through the caspase-8-mediated activation of cardiomyocyte PANoptosis and highlight that Piezo1 may represent a new target for treating ischaemic heart disease.

Bifunctional Chiral Electrocatalysts Enable Enantioselective α-Alkylation of Aldehydes.

Herein, we describe an innovative approach to the asymmetric electrochemical α-alkylation of aldehydes facilitated by a newly designed bifunctional chiral electrocatalyst. The highly efficient bifunctional chiral electrocatalyst combines a chiral aminocatalyst with a redox mediator. It plays a dual role as a redox mediator for electrooxidation, while simultaneously providing remarkable asymmetric induction for the stereoselective α-alkylation of aldehydes. Additionally, this novel catalyst exhibits enhanced catalytic activity and excellent stereoselective control comparable to conventional catalytic systems. As a result, this strategy provides a new avenue for versatile asymmetric electrochemistry. The electrooxidation of diverse phenols enables the C-H/C-H oxidative α-alkylation of aldehydes in a highly chemo- and stereoselective fashion. Detailed mechanistic studies by control experiments and cyclic voltammetry analysis demonstrate possible reaction pathways and the origin of enantio-induction.

Esketamine mitigates mechanical ventilation-induced lung injury in chronic obstructive pulmonary disease rats via inhibition of the MAPK/NF-κB signaling pathway and reduction of oxidative stress.

PURPOSE: To investigate esketamine's impact on inflammation and oxidative stress in ventilated chronic obstructive pulmonary disease (COPD) rats, examining its regulatory mechanisms. METHODS: Rats were divided into four groups: control group (Con), COPD model group (M), COPD model with saline treatment group (M+S), and COPD model with esketamine treatment group (M+K), with 12 rats in each group. After two months, all rats underwent anesthesia and mechanical ventilation. Group M+K received 5 mg/kg esketamine intravenously, while Group M+S received the same volume of saline. Lung tissues were collected for analysis two hours later, including airway peak pressure, wet-to-dry(W/D) ratio, lung permeability index(LPI), hematoxylin and eosin(H&E) staining, and transmission electron microscopy(TEM). Tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), interleukin-8(IL-8), and interleukin-10(IL-10) levels were determined by enzyme-linked immunosorbent assay(ELISA); phosphorylated Nuclear Factor Kappa B(p-NF-κB), mitogen-activated protein kinase 14(p38), phosphorylated p38 (p-p38), c-Jun N-terminal kinase(JNK), and phosphorylated JNK (p-JNK) expressions by Western blotting and immunohistochemistry; and malondialdehyde(MDA), myeloperoxidase(MPO), and superoxide dismutase(SOD) levels were also measured by corresponding biochemical assays. RESULTS: Lung specimens from groups M, M+S, and M+K manifested hallmark histopathological features of COPD. Compared with group Con, group M displayed increased peak airway pressure, W/D ratio, and LPI. In group M+K, compared with group M, esketamine significantly reduced the W/D ratio, LPI, and concentrations of pro-inflammatory cytokines TNF-α, IL-6, and IL-8 while concurrently elevating IL-10 levels. Furthermore, the treatment attenuated the activation of the NF-κB and MAPK pathways, indicated by decreased levels of p-NF-κB, p-p38, and p-JNK.Additionally, compared to group M, group M+K showed decreased MDA and MPO levels and increased SOD levels in lung tissue. CONCLUSION: Esketamine attenuates mechanical ventilation-induced lung injury in COPD rat models by inhibiting the MAPK/NF-κB signaling pathway and reducing oxidative stress.

The safety and efficacy of five surgical treatments in prostate enucleation: a network meta-analysis.

PURPOSE: The aim of our study was to investigate the comparative outcomes of five different energy types on surgical efficacy and postoperative recovery in patients with benign prostate hyperplasia. METHODS: The literature was systematically reviewed on December 1st, 2023, encompassing studies retrieved from PubMed, Embase, Web of Science, and The Cochrane Library databases that incorporated clinical studies of holmium laser enucleation of the prostate (HoLEP), Thulium:YAG laser enucleation of the prostate (ThuLEP), transurethral plasmakinetic enucleation of prostate (PKEP), diode laser enucleation of the prostate (DiLEP) and thulium fiber laser enucleation of the prostate (ThuFLEP) in the treatment of prostatic hyperplasia. Two independent reviewers extracted study data and conducted quality assessments using the Cochrane Collaboration's Risk of Bias tool and Newcastle-Ottawa Scale (NOS). Network meta-analysis (NMA) was employed to indirectly analyze the outcomes of endoscopic enucleation of the prostate (EEP) techniques. RESULTS: The study included a total of 38 studies, comprising 21 non-randomized controlled trials (nRCTs) and 17 randomized controlled trials (RCTs), incorporating five distinct techniques: holmium laser, Thulium:YAG laser, bipolar plasma, diode laser and thulium fiber laser. In comparing treatment durations, ThuLEP and HoLEP had shorter overall hospital stays than PKEP, while the enucleation time of ThuLEP and HoLEP was shorter than that of ThuFLEP. Moreover, the enucleation tissue weight of both thulium fiber laser and holmium laser was heavier than bipolar plasma. However, the analysis did not reveal any statistically significant variation in complications among the various types of enucleation. In postoperative follow-up, the IPSS at 3 months post-operation was superior in the Thulium:YAG laser group compared to the holmium laser group. The thulium fiber laser technique demonstrated significant advantages over other enucleation methods in terms of QoL and PVR at 12 months after surgery. CONCLUSION: Theoretical properties may vary among different energy sources; however, there are no discernible clinical differences in operation-related parameters, postoperative complications, and postoperative follow-up. Therefore, the choice of laser does not significantly impact the outcome. However, due to the limited number of included studies, future research should focus on larger sample sizes and multicenter investigations to further validate the findings of this study.

De novo transcriptome analysis of Protohermes xanthodes Navás (Megaloptera: Corydalidae) reveling the effects of sublethal chlorpyrifos on the expression of cholinergic neuronal genes.

The insect cholinergic neuron system is the target for various pesticides, including organophosphate, carbamate and neonicotinoid pesticides. In this study, we conducted a de novo transcriptome analysis on the aquatic insect Protohermes xanthodes and identified for the first time presenting sixteen genes encoding cholinergic neuronal proteins (PxanChaT, PxanVAChT, PxanmAChR, PxannAChRs, and PxanAChEs), which are candidates for acetylcholine synthesis, transport, reception and degradation in cholinergic synapse. FPKM analysis revealed that these genes are primarily expressed in head and nerve cord of P. xanthodes larvae, and some of them are also abundant in hindgut, malpighian tubules and tracheae. After exposed to different concentrations of sublethal chlorpyrifos (CPF), expression of these cholinergic neuronal genes are generally increased and then decreased with the increase of CPF concentration, except PxannAChRα9 which is increased in both 4.2 and 8.4 µg/L CPF groups. Short-term (96 h) CPF exposure resulted in significant up-regulation of PxanAChE1 expression in P. xanthodes larvae exposed to 0.42 and 4.2 µg/L CPF concentrations, while PxanAChE2 was up-regulated only in 0.42 µg/L CPF group. After long-term (14 d) CPF exposure, PxanAChE1 expression was down-regulated in 0.168 and 0.42 µg/L CPF groups. PxanAChE2 expression was dramatically decreased in all CPF groups. Moreover, acetylcholinesterase (AChE) activity was significantly decreased across all long-term CPF exposure groups. These results suggested that sublethal exposure to CPF can disrupt the expression of cholinergic neuronal genes in P. xanthodes larvae, and implied that long-term sublethal CPF exposure may cause toxic effects on P. xanthodes larvae by inhibiting AChE activity. Furthermore, identification of cholinergic neuronal genes in P. xanthodes provided candidate molecular markers for study the toxic effects of environmental pollutants on the neuron system of an aquatic predatory insect with ecological importance.

Tissue Accumulation and Biotransformation of 6PPD-Quinone in Adult Zebrafish and Its Effects on the Intestinal Microbial Community.

The pronounced lethality of N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-quinone or 6PPDQ) toward specific salmonids, while sparing other fish species, has received considerable attention. However, the underlying cause of this species-specific toxicity remains unresolved. This study explored 6PPDQ toxicokinetics and intestinal microbiota composition in adult zebrafish during a 14-day exposure to environmentally realistic concentrations, followed by a 7-day recovery phase. Predominant accumulation occurred in the brain, intestine, and eyes, with the lowest levels in the liver. Six metabolites were found to undergo hydroxylation, with two additionally undergoing O-sulfonation. Semiquantitative analyses revealed that the predominant metabolite featured a hydroxy group situated on the phenyl ring adjacent to the quinone. This was further validated by assessing enzyme activity and determining in silico binding interactions. Notably, the binding affinity between 6PPDQ and zebrafish phase I and II enzymes exceeded that with the corresponding coho salmon enzymes by 1.04-1.53 times, suggesting a higher potential for 6PPDQ detoxification in tolerant species. Whole-genome sequencing revealed significant increases in the genera Nocardioides and Rhodococcus after exposure to 6PPDQ. Functional annotation and pathway enrichment analyses predicted that these two genera would be responsible for the biodegradation and metabolism of xenobiotics. These findings offer crucial data for comprehending 6PPDQ-induced species-specific toxicity.

Comparative analysis of new, mScarlet-based red fluorescent tags in Caenorhabditis elegans.

One problem that has hampered the use of red fluorescent proteins in the fast-developing nematode C. elegans has been the substantial time delay in maturation of several generations of red fluorophores. The recently described mScarlet-I3 protein has properties that may overcome this limitation. We compare here the brightness and maturation time of CRISPR/Cas9 genome-engineered mScarlet, mScarlet3, mScarlet-I3 and GFP reporter knock-ins. Comparing the onset and brightness of expression of reporter alleles of C. elegans golg-4, encoding a broadly expressed Golgi resident protein, we found that the onset of detection of mScarlet-I3 in the embryo is several hours earlier than older versions of mScarlet and comparable to GFP. These findings were further supported by comparing mScarlet-I3 and GFP reporter alleles for pks-1, a gene expressed in the CAN neuron and cells of the alimentary system, as well as reporter alleles for the panneuronal, nuclear marker unc-75. Hence, the relative properties of mScarlet-I3 and GFP do not depend on cellular or subcellular context. In all cases, mScarlet-I3 reporters also show improved signal-to-noise ratio compared to GFP.

Verteporfin suppressed mitophagy via PINK1/parkin pathway in endometrial cancer.

Endometrial cancer (EC) is a malignancy that poses a threat to woman's health worldwide. Building upon prior work, we explored the inhibitory effect of verteporfin on EC. We showed that verteporfin can damage the mitochondria of EC cells, leading to a decrease of mitochondrial membrane potential and an increase in ROS (reactive oxygen species). In addition, verteporfin treatment was shown to inhibit the proliferation and migration of EC cells, promote apoptosis, and reduce the expression of mitophagy-related proteins PINK1/parkin and TOM20. The ROS inhibitor N-Acetyl Cysteine was able to rescue the expression of PINK1/parkin proteins. This suggests that verteporfin may inhibit mitophagy by elevating ROS levels, thereby inhibiting EC cell viability. The effect of verteporfin on mitophagy supports further investigation as a potential therapeutic option for EC.

Three-dimensional analysis of the positional relationship between the dentition and basal bone region in patients with skeletal Class I and Class II malocclusion with mandibular retrusion.

Objective: This study aimed to determine the maxillary and mandibular basal bone regions and explore the three-dimensional positional relationship between the dentition and basal bone regions in patients with skeletal Class I and Class II malocclusions with mandibular retrusion. Methods: Eighty patients (40 each with Class I and Class II malocclusion) were enrolled. Maxillary and mandibular basal bone regions were determined using cone-beam computed tomography images. To measure the relationship between the dentition and basal bone region, the root position and root inclination were calculated using the coordinates of specific fixed points by a computer program written in Python. Results: In the Class II group, the mandibular anterior teeth inclined more labially (P < 0.05), with their apices positioned closer to the external boundary. The apex of the maxillary anterior root was positioned closer to the external boundary in both groups. Considering the molar region, the maxillary first molars tended to be more lingually inclined in females (P = 0.037), whereas the mandibular first molars were significantly more labially inclined in the Class II group (P < 0.05). Conclusions: Mandibular anterior teeth in Class II malocclusion exhibit a compensatory labial inclination trend with the crown and apex relative to the basal bone region when mandibular retrusion occurs. Moreover, as the root apices of the maxillary anterior teeth are much closer to the labial side in Class I and Class II malocclusion, the range of movement at the root apex should be limited to avoid extensive labial movement.