Correlation between Pain and Anal Defecation Function in Postoperative Patients with Colorectal Cancer and Related Factors Affecting Patients' Prognosis.

BACKGROUND: The degree of postoperative pain and defecation function in colorectal cancer will affect patients' prognosis. Therefore, exploring the correlation between postoperative pain and defecation function, and analyzing the related factors, will help to improve the quality of patients' prognosis. METHODS: A total of 94 patients with colorectal cancer admitted to our hospital from March 2022 to June 2023 were retrospectively selected for study. The visual analog scale (VAS) was used to evaluate the pain level of the patients. The low anterior resection syndrome (LARS) scale was used to evaluate bowel function of the patients, and the incidence of LARS was recorded. The patients were grouped according to whether or not they had the complications of LARS, and they were divided into the groups of concurrent LARS and non-concurrent LARS. The patients' anorectal pressure was measured, and the measurements included maximum tolerated volume (MTV), anorectal resting pressure (ARP), and maximum squeeze pressure (MSP). Pearson's correlation coefficient was used to test associations between anal defecation function and postoperative pain and anorectal manometry. Logistic regression was used to test predictors of concurrent LARS, and the value of each of the indices for prediction of LARS was examined using the receiver operating characteristic (ROC). RESULTS: Patients' VAS scores were positively correlated with LARS scores (p < 0.05). A total of 22 patients with VAS score ≥20 points were found to have a LARS incidence of 23.40% based on the LARS score. The VAS score was higher in the concurrent LARS group than in the non-concurrent LARS group (p < 0.05). The concurrent LARS group had a higher percentage of patients with age ≥60 years, body mass index ≥24 kg/m2, anastomotic position <5 cm from the anal verge, preoperative radiotherapy, and anastomotic fistula than the non-current LARS group (p < 0.05). The levels of MTV, ARP, and MSP were lower in patients in the concurrent LARS group than in the non-current LARS group (p < 0.05). Patients' LARS scores were negatively correlated with MTV (r = -0.420), ARP (r = -0.300) and MSP (r = -0.220) levels (p < 0.05). Logistic regression analysis showed that anastomotic position <5 cm from the anal verge, preoperative radiotherapy, anastomotic fistula, high VAS level, and low MTV level were all significant predictors of concurrent LARS. Anastomotic position, whether or not radiotherapy was administered preoperatively, anastomotic fistula, VAS score, and MSP level all had high sensitivity and specificity for prediction of concurrent LARS, and the combined area under the curve (AUC) of each index was 0.921, sensitivity was 0.818, and specificity was 0.944. CONCLUSION: LARS is strongly associated with the patient's pain level, and factors such as anastomotic position <5 cm from the anal verge, preoperative radiotherapy, anastomotic fistula, high VAS level, and low MTV level will increase the risk of concurrent LARS in patients.

Melatonin-induced physiology and transcriptome changes in banana seedlings under salt stress conditions.

Soil salinization poses a serious threat to the ecological environment and agricultural production and is one of the most common abiotic stresses in global agricultural production. As a salt-sensitive plant, the growth, development, and production of bananas (Musa acuminata L.) are restricted by salt stress. Melatonin is known to improve the resistance of plants to stress. The study analyzed the effects of 100 µM melatonin on physiological and transcriptome changes in banana varieties (AAA group cv. Cavendish) under 60 mmol/l of NaCl salt stress situation. The phenotypic results showed that the application of exogenous melatonin could maintain banana plants' health growth and alleviate the damage caused by salt stress. The physiological data show that the application of exogenous melatonin can enhance salt tolerance of banana seedlings by increasing the content of proline content and soluble protein, slowing down the degradation of chlorophyll, reducing membrane permeability and recovery of relative water content, increasing the accumulation of MDA, and enhancing antioxidant defense activity. Transcriptome sequencing showed that melatonin-induced salt tolerance of banana seedlings involved biological processes, molecular functions, and cellular components. We also found that differentially expressed genes (DEGs) are involved in a variety of metabolic pathways, including amino sugar and nucleotide sugar metabolism, phenylalanine metabolism, cyanoamino acid metabolism, starch and sucrose metabolism, and linoleic acid metabolism. These major metabolism and biosynthesis may be involved in the potential mechanism of melatonin under salt stress. Furthermore, some members of the transcription factor family, such as MYB, NAC, bHLH, and WRKY, might contribute to melatonin alleviating salt stress tolerance of the banana plant. The result laid a basis for further clarifying the salt stress resistance mechanism of bananas mediated by exogenous melatonin and provides theoretical bases to utilize melatonin to improve banana salt tolerance in the future.

A robust H∞-based steering assistance system for the wheeled tractor.

Agricultural machine automatic navigation poses great challenge to the precise agricultural technology system nowadays. To this end, this paper proposes a novel steering assistance system (SAS) to assist drivers in the path-tracking. First, the driver steering model is investigated through the driver simulator tests. Combining the wheeled tractor kinematics model, a driver-vehicle model is developed. Then, a polytopic linear parameter-varying (LPV) system is adopted to describe the uncertainties, including time-varying driver model parameters and velocity, in the model, based on which an output-feedback robust controller is developed to ensure robust stability within the polytope space. Moreover, a regional pole placement method is adopted to improve the transient performance of the system. Finally, driver-in-the-loop and field tests conducted to value the controller. The results show the effectiveness of the proposed method to improve the path-tracking performance for the agricultural machine navigation, while reducing the physical and mental workload of drivers. This control method is expected to be a paradigm for the precise navigation system of the agricultural machinery.

Mangostanin Derivatives as Novel and Orally Active Phosphodiesterase 4 Inhibitors for the Treatment of Idiopathic Pulmonary Fibrosis with Improved Safety.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease, and its incidence rate is rapidly rising. However, effective therapies for the treatment of IPF are still lacking. Phosphodiesterase 4 (PDE4) inhibitors were reported to be potential anti-fibrotic agents, but their clinical use was hampered by side effects like emesis and nausea. Herein, structure-based hit-to-lead optimizations of natural mangostanin resulted in the novel and orally active PDE4 inhibitor 18a with potent inhibitory affinity (IC50 = 4.2 nM), favorable physico-chemical properties, and a different binding pattern from roflumilast. Emetic activity tests on dogs demonstrated that 18a cannot cause emesis even at an oral dose of 10 mg/kg, whereas rolipram had severe emetic effects at an oral dose of 1 mg/kg. Finally, the oral administration of 18a (10 mg/kg) exhibited comparable anti-pulmonary fibrosis effects with pirfenidone (150 mg/kg) in a bleomycin-induced IPF rat model, indicating its potential as a novel anti-IPF agent with improved safety.

MSPAN: A Memristive Spike-Based Computing Engine With Adaptive Neuron for Edge Arrhythmia Detection.

In this work, a memristive spike-based computing in memory (CIM) system with adaptive neuron (MSPAN) is proposed to realize energy-efficient remote arrhythmia detection with high accuracy in edge devices by software and hardware co-design. A multi-layer deep integrative spiking neural network (DiSNN) is first designed with an accuracy of 93.6% in 4-class ECG classification tasks. Then a memristor-based CIM architecture and the corresponding mapping method are proposed to deploy the DiSNN. By evaluation, the overall system achieves an accuracy of over 92.25% on the MIT-BIH dataset while the area is 3.438 mm2 and the power consumption is 0.178 µJ per heartbeat at a clock frequency of 500 MHz. These results reveal that the proposed MSPAN system is promising for arrhythmia detection in edge devices.

Design, Synthesis, and Biological Evaluation of Novel Multifunctional Rolipram-Tranilast Hybrids As Potential Treatment for Traumatic Brain Injury.

Traumatic brain injury (TBI) is a prevalent public healthcare concern frequently instigated by mechanical shock, traffic, or violence incidents, leading to permanent nerve damage, and there is no ideal treatment for it yet. In this study, a series of Rolipram-Tranilast hybrids were designed and synthesized. The neuroprotective activities of the Rolipram-Tranilast hybrids were evaluated both in vitro and in vivo. Compound 5 has been identified as the strongest neuroprotective molecule among the series with robust anti-oxidant and anti-inflammatory potentials. Compound 5 significantly increased the heme oxygenase-1 (HO-1) levels and the phosphorylated cAMP response elements binding protein (p-CREB) while it down-regulated phosphodiesterase-4 B (PDE4B) expression in vitro. Furthermore, compound 5 remarkably attenuated TBI and had a good safety profile in mice. Taken together, our findings suggested that compound 5 could serve as a novel promising lead compound in the treatment of TBI and other central nervous system (CNS) diseases associated with PDE4B and oxidative stress.

Discovery and Optimization of α-Mangostin Derivatives as Novel PDE4 Inhibitors for the Treatment of Vascular Dementia.

To validate PDE4 inhibitors as novel therapeutic agents against vascular dementia (VaD), 25 derivatives were discovered from the natural inhibitor α-mangostin (IC50 = 1.31 µM). Hit-to-lead optimization identified a novel and selective PDE4 inhibitor 4e (IC50 = 17 nM), which adopted a different binding pattern from PDE4 inhibitors roflumilast and rolipram. Oral administration of 4e at a dose of 10 mg/kg exhibited remarkable therapeutic effects in a VaD model and did not cause emesis to beagle dogs, indicating its potential as a novel anti-VaD agent.

A Tailored Multifunctional Anticancer Nanodelivery System for Ruthenium-Based Photosensitizers: Tumor Microenvironment Adaption and Remodeling.

Ruthenium complexes are promising photosensitizers (PSs), but their clinical applications have many limitations. Here, a multifunctional nano-platform PDA-Pt-CD@RuFc formed by platinum-decorated and cyclodextrin (CD)-modified polydopamine (PDA) nanoparticles (NPs) loaded with a ferrocene-appended ruthenium complex (RuFc) is reported. The NPs can successfully deliver RuFc to the tumor sites. The release of RuFc from the NPs can be triggered by low pH, photothermal heating, and H2O2. The combined photodynamic and photothermal therapy (PDT-PTT) mediated by PDA-Pt-CD@RuFc NPs can overcome the hypoxic environment of tumors from several aspects. First, the platinum NPs can catalyze H2O2 to produce O2. Second, vasodilation caused by photothermal heating can sustain the oxygen supplement. Third, PDT exerted by RuFc can also occur through the non-oxygen-dependent Fenton reaction. Due to the presence of PDA, platinum NPs, and RuFc, the nanosystem can be used in multimodal imaging including photothermal, photoacoustic, and computed tomography imaging. The NPs can be excited by the near-infrared two-photon light source. Moreover, the combined treatment can improve the tumor microenvironments to obtain an optimized combined therapeutic effect. In summary, this study presents a tumor-microenvironment-adaptive strategy to optimize the potential of ruthenium complexes as PSs from multiple aspects.

3ß-Acetyloxy-oleanolic Acid Attenuates Pristane-Induced Lupus Nephritis by Regulating Th17 Differentiation.

Th17 activity has been implicated in systemic lupus erythematosus (SLE), which is a systemic autoimmune disease with a typical clinical manifestation of lupus nephritis (LN). Retinoic acid receptor-related orphan receptor gamma t (RORγt) has been shown to be important for Th17 differentiation. In this study, we evaluated the inhibition of RORγt activity by 3ß-acetyloxy-oleanolic acid (AOA), a small molecule isolated from the root of Symplocos laurina, a traditional herb belonging to South China. We demonstrated that AOA can inhibit RORγt activity and prevent SLE pathogenesis in a pristane-induced LN model. The results showed that AOA decreased RORγt transcription activity in a reporter assay and prevented Th17 differentiation in vitro. In vivo studies showed that AOA treatment decreased serum anti-dsDNA antibody and alleviated renal pathologic damage as well as antibody complex accumulation in the pristane-induced LN model. These results demonstrated that AOA can improve the clinical manifestation of LN, indicating potential application in SLE therapy.

Mitochondria-Accumulating Rhenium(I) Tricarbonyl Complexes Induce Cell Death via Irreversible Oxidative Stress and Glutathione Metabolism Disturbance.

Mitochondria play a critical role in tumorigenesis. Targeting mitochondria and disturbing related events have been emerging as a promising way for chemotherapy. In this work, two binuclear rhenium(I) tricarbonyl complexes of the general formula [Re2(CO)6(dip)2L](PF6)2 (dip = 4,7-diphenyl-1,10-phenanthroline; L = 4,4'-azopyridine (ReN) or 4,4'-dithiodipyridine (ReS)) were synthesized and characterized. ReN and ReS can react with glutathione (GSH). They exhibit good in vitro anticancer activity against cancer cell lines screened. Besides, they can target mitochondria, cause oxidative stress, and disturb GSH metabolism. Both ReN and ReS can induce necroptosis and caspase-dependent apoptosis simultaneously. We also demonstrate that ReN and ReS can inhibit tumor growth in nude mice bearing carcinoma xenografts. Our study shows the potential of Re(I) complexes as chemotherapeutic agents to kill cancer cells via a mitochondria-to-cellular redox strategy.

Isolation, Characterization, and Phylogenetic Analysis of Two New Crimean-Congo Hemorrhagic Fever Virus Strains from the Northern Region of Xinjiang Province, China.

Crimean-Congo hemorrhagic fever (CCHF) caused by the CCHF virus (CCHFV) is a tick-borne natural focal disease with a mortality rate of approximately 50%. CCHFV is widely prevalent in Africa, southern Asia, the Middle East, and southeast Europe. CCHF outbreaks have been reported previously in Xinjiang province, China, especially in its southern region. Epidemiological surveys conducted on ticks and animals have revealed the presence of CCHFV strains in ticks, rodents, and infected individuals from cities and counties in southern Xinjiang. Phylogenetic analyses revealed that the Chinese CCHFV strains belong to one genotype, based on complete sequences of the S segments of its negative-stranded RNA genome. The present study reports two new CCHFV strains isolated from Hyalomma asiaticum asiaticum ticks collected from Fukang City and Wujiaqu City in the northern region of Xinjiang. Viral characteristics and their evolutionary relationships were analyzed through metagenomic and reverse-transcription PCR analyses; these analyses indicated that the genotype of both strains was different from that of other Chinese strains. Furthermore, previous reports of CCHFV in Xinjiang were reviewed and phylogenetic analyses were performed. CCHFV was found to prevail in Fukang City in Junggar Basin for more than 20 years, and that Fukang City and Wujiaqu City are considered natural reservoirs of different genotypes of CCHFV strains. Our findings facilitate the understanding of CCHFV distribution in Xinjiang province and provide insights into the evolutionary relationships among Chinese CCHFV strains.