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• The study establishes a novel assay for simultaneous detection of feline parvovirus and feline coronavirus. • SYBR Green І-based duplex real-time qPCR method was established with high sensitivity, specificity and reliability. • It provides a tool that could be beneficial for clinical diagnostics of feline parvovirus and feline coronavirus coinfection. Feline coronavirus (FCoV) contains two serotypes, feline enteric coronavirus (FECV) and Feline infectious peritonitis virus (FIPV). FECV and feline parvovirus (FPV) can cause similar clinical symptoms in cats, such as diarrhea. The objective of this study was to establish a duplex SYBR Green I-based quantitative polymerase chain reaction (qPCR) assay for rapid and simultaneous detection of FPV and FCoV. Two pairs of specific PCR primers were designed to target fragments of the VP2 gene of FPV and of the 5′ UTR gene of FCoV, respectively. The assay distinguished between the two viruses based on the melting curves (melting temperatures 77.0 ± 0.5 °C [FPV] and 80.5 ± 0.5 °C [FCoV]). The minimum limits of FPV and FCoV detection were 4.74 × 101 copies/μL and 7.77 × 101 copies/μL, respectively. The assay showed excellent reproducibility and reliability, based on the mean coefficient of variation. In conclusion, this novel duplex SYBR Green I-based qPCR assay is sensitive and can specifically, reliably, and rapidly detect FPV and FCoV (co-)infections. [ABSTRACT FROM AUTHOR]

[Display omitted] • Knock-out one allele of miR-96 causes mechanical and thermal allodynia in mice. • Increased spinal Na v 1.7, 1.8, 1.9, 1.2 contributes to allodynia in miR-96 KO mice. • Intrathecal injection of Na v 1.7 or 1.8 blocker relieves allodynia of miR-96 KO mice. • Gad2::CreERT2 conditional miR-96 knockout mice phenocopies global knockout mice. • Nerve injury induces loss of miR-96 and de-repression of Na v s in GABAergic neurons. Voltage-gated sodium channels (Na v s) 1.7, 1.8, and 1.9 are predominately expressed in peripheral sensory neurons and are critical for action potential propagation in nociceptors. Unexpectedly, we found that expression of SCN9A, SCN10A, SCN11A, and SCN2A, the alpha subunit of Na v 1.7, Na v 1.8, Na v 1.9 and Na v 1.2, respectively, are up-regulated in spinal dorsal horn (SDH) neurons of miR-96 knockout mice. These mice also have de-repression of CACNA2D1/2 in DRG and display thermal and mechanical allodynia that could be attenuated by intrathecal or intraperitoneal injection of Na v 1.7 or Na v 1.8 blockers or Gabapentin. Moreover, Gad2::CreERT2 conditional miR-96 knockout mice phenocopied global knockout mice, implicating inhibitory neurons; nerve injury induced significant loss of miR-96 in SDH GABAergic and Glutamatergic neurons in mice which negatively correlated to up-regulation of Na v 1.7, Na v 1.8, Na v 1.9 and Scn2a , this dis-regulation of miR-96 and Na v s in SDH neurons contributed to neuropathic pain which can be alleviated by intrathecal injection of Na v 1.7 or Na v 1.8 blockers. In conclusion, miR-96 is required to avoid allodynia through limiting the expression of VGCCs and Na v s in DRG and Na v s in SDH in naïve and nerve injury-induced neuropathic pain mice. Our findings suggest that central nervous system penetrating Na v 1.7 and Na v 1.8 blockers may be efficacious for pain relief. [ABSTRACT FROM AUTHOR]

Endothelin-1 (ET-1) and its receptors (ETAR/ETBR) emerge to be a key signaling axis in neuropathic pain processing and are recognized as new therapeutic targets. Yet, little is known on the functional regulation of ET-1 axis during neuropathic pain. Bioinformatics analysis indicated that paired box gene 2 (Pax2) or nuclear factor of activated T-cells 5 (NFAT5), two transcription factors involved in the modulation of neurotransmission, may regulate ET-1. Therefore, we hypothesized that ET-1 axis may be regulated by Pax2 or NFAT5 in the development of neuropathic pain. After partial sciatic nerve ligation (pSNL), rats displayed allodynia and hyperalgesia, which was associated with increased mRNA and protein expressions of spinal Pax2, NFAT5, and mRNA levels of ET-1 and ETAR, but not ETBR. Knockdown of Pax2 or NFAT5 with siRNA, or inhibition of ETAR with BQ-123 attenuated pSNL-induced pain-like behaviors. At molecular level, Pax2 siRNA, but not NFAT5 siRNA, downregulated ET-1 and ETAR, while ETAR inhibitor reduced NFAT5, indicating Pax2 in the upstream of ET-1 axis with NFAT5 in the downstream. Further, suppression of Pax2 (inhibiting ET-1) or impairment of ET-1 signaling (inhibition of ETAR and/or decrease of NFAT5) deactivated mitogen-activated protein kinases (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways, supporting the significance of functional regulation of ET-1 axis in neuropathic pain signaling. These findings demonstrate that Pax2 targeting ET-1–ETAR–NFAT5 is a novel regulatory mechanism underlying neuropathic pain. [ABSTRACT FROM AUTHOR]

Iterative learning control (ILC) is an effective technique that improves the tracking performance of systems by adjusting the feedforward control signal based on the memory data. The key in ILC is to design learning filters with guaranteed convergence and robustness, which usually involves lots of tuning effort especially in high-order ILC. To facilitate this procedure, this paper proposes a systematics approach to design learning filters for arbitrary-order ILC with guaranteed convergence, robustness and ease of tuning. The filter design problem is transformed into an H ∞ optimal control problem for a constructed feedback system. This approach is based on an infinite impulse response (IIR) system and conducted directly in iteration-frequency domain. The proposed algorithm is further advanced to the one that explicitly considers system variations based on μ synthesis. Important characteristics of the proposed approach such as convergence and robustness are explored and demonstrated through both simulations and experiments on a wafer scanning system. [ABSTRACT FROM AUTHOR]

Purpose: Transanal total mesorectal excision (taTME) is a promising surgical procedure for middle and low rectal cancer; however, it is linked to significant morbidity. This study aimed to determine the incidence of postoperative surgical complications and anastomotic leakage following taTME and to identify their associated risk factors. Methods: The prospective clinical data of 114 patients, who underwent taTME and primary anastomosis for mid-low rectal cancer between November 2016 and June 2022, were retrospectively analyzed. Univariate and multivariate analyses were performed to identify clinical characteristics and risk factors for predicting surgical complications and anastomotic leakage. Results: Surgical complications occurred in 40 (35.1%) patients within the first 30 days following surgery. Based on the Clavien–Dindo classification, minor complications (Clavien–Dindo grades I + II) accounted for 30.7%, while major complications (Clavien–Dindo grades III + IV) accounted for only 4.4%. None of the patients died within 30 days. The incidence of anastomotic leakage was 15.8%: 4.4% as grade A (5 cases), 9.6% as grade B (11 cases), and 1.8% as grade C (2 cases). Preoperative T3-4 was identified as an independent risk factor for surgical complications (p = 0.031) by multivariate analysis. American Society of Anesthesiology score ≥ 3 (P = 0.021) and incomplete total mesorectal excision specimens (P = 0.030) were significantly associated with the risk of anastomotic leakage. Conclusions: In this study, the incidence of surgical complications and anastomotic leakage in taTME aligned with previously reported rates. Preoperative T3-4 was significantly associated with surgical complications. American Society of Anesthesiology score ≥ 3 and incomplete TME specimens independently increased the risk of anastomotic leakage. [ABSTRACT FROM AUTHOR]

Conventional reconnaissance camera systems have been flown on manned aircraft, where the weight, size, and power requirements are not stringent. However, today, these parameters are important for unmanned aerial vehicles (UAVs). This article provides a solution to the design of airborne large aperture infrared optical systems, based on a monocentric lens that can meet the strict criteria of aerial reconnaissance UAVs for a wide field of view (FOV) and lightness of airborne electro-optical pod cameras. A monocentric lens has a curved image plane, consisting of an array of microsensors, which can provide an image with 368 megapixels over a 100° FOV. We obtained the initial structure of a five-glass (5GS) asymmetric monocentric lens with an air gap, using ray-tracing and global optimization algorithms. According to the design results, the ground sampling distance (GSD) of the system is 0.33 m at 3000 m altitude. The full-field modulation transfer function (MTF) value of the system is more than 0.4 at a Nyquist frequency of 70 lp/mm. We present a primary thermal control method, and the image quality was steady throughout the operating temperature range. This compactness and simple structure fulfill the needs of uncrewed airborne lenses. This work may facilitate the practical application of monocentric lens in UAVs. [ABSTRACT FROM AUTHOR]

Purpose: As transanal total mesorectal excision (taTME) is performed worldwide, the optimization of existing training and guidance programs to enhance new taTME learners' competence in performing this procedure is warranted. This study aimed to evaluate the taTME learning curve in patients with mid-low rectal cancer. Methods: Patients who underwent taTME for mid-low rectal cancer between October 2015 and August 2021 at a single center were included. A cumulative sum (CUSUM) learning curve analysis was performed with the total operation time as the study outcome. The learning curve was analyzed using risk-adjusted CUSUM analysis, with postoperative complications and anastomotic leakage (AL) as outcomes. Results: In total, 104 consecutive patients were included in this study. The CUSUM learning curve for total operative time started declining after 42 cases (309.1 ± 84.4 vs. 220.2 ± 46.4, P < 0.001). The risk-adjusted CUSUM (RA-CUSUM) learning curve for postoperative complications fluctuated in cases 44–75 and declined significantly after case 75. The RA-CUSUM learning curve for AL declined after 68 cases. Conclusions: taTME had learning curves of 42, 75, and 68 cases for total operative time, postoperative complications, and AL, respectively. A surgeon may require 42 and 75 cases to achieve "proficiency" and "mastery" in taTME procedures, respectively. [ABSTRACT FROM AUTHOR]

The double excited state intramolecular proton transfer (ESIPT) mechanisms of porphycene, were theoretically studied. The primary bond lengths, IR vibrational spectra and hydrogen-bond energy indicate that the intramolecular hydrogen bonds were strengthened in the first excited state, which facilitate the ESIPT processes. To elucidate the proposed mechanism, the potential-energy surfaces of the ground state and first excited state were constructed as functions of N H bond lengths and its relative torsional angle rotation. The intramolecular proton transfer of prophycene is more likely to occur through lengthwise pathway and proceed in the concerted coordinated transfer manner. [ABSTRACT FROM AUTHOR]

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that can promote the development and proliferation of neurons. BDNF has been found to be involved in male reproduction. Leydig cells in testicular interstitial tissues can secrete testosterone in a luteinizing hormone-dependent manner. We showed that BDNF and its receptor TrkB were expressed in mice TM3 Leydig cells in the present study. Furthermore, BDNF can promote proliferation of mouse TM3 Leydig cells in vitro. Results of microRNA (miRNA) deep sequencing showed that BDNF can alter the expression profile of miRNAs in TM3 Leydig cells. Eighty-three miRNAs were significantly different in the BDNF-treated and control groups (fold change of >2.0 or <0.5, P < 0.05) wherein 40 were upregulated and 43 were downregulated. The expression levels of miR-125a-5p, miR-22-5p, miR-342-59, miR-451a, miR-148a-5p, miR-29b-3p, miR-199b-5p, and miR-145a-5p were further confirmed by quantitative real-time polymerase chain reaction. Bioinformatic analysis revealed that miRNAs regulated a large number of genes with different functions. Pathway analysis indicated that miRNAs participate in the pathways involved in signal transduction, cancer, metabolism, endocrine system, immune system, and nerve system. This study indicated that miRNAs might be involved in the BDNF-regulated cellular functions of Leydig cells. [ABSTRACT FROM AUTHOR]

Abstract: The 5-HT2A receptor (5-HT2AR) is implicated in psychotropic changes within the central nervous system (CNS). A number of polymorphisms have been reported in the 5-HT2AR gene; one of these results in a non-synonymous change, H452Y, in the carboxy-terminal tail of the receptor protein. The minor allele (9% occurrence) has been statistically associated with CNS dysfunction such as impaired memory processing and resistance to neuroleptic treatment in schizophrenic patients. We investigated the impact of H452Y mutation of the 5-HT2AR expressed in COS7 cells on distinctly coupled intracellular signalling pathways from the receptor, focusing on the heterotrimeric G protein-independent phospholipase D (PLD) pathway, compared to the conventional Gq/11-linked phospholipase C (PLC) pathway. The H452Y mutation selectively attenuated PLD signalling, which as in the wild-type receptor, was mediated by a molecular complex involving PLD1 docked to the receptor''s carboxy-terminal tail domain. Co-immunoprecipitation and GST-fusion protein experiments revealed that the H452Y mutation selectively reduced PLD1 binding to the receptor. Experiments with blocking peptides to mimic short sections of the 5-HT2AR tail sequence revealed that the peptide spanning residue 452 strongly reduced PLD but not PLC responses of the receptor. Similar observations were made when assessing both PLD responses and PLD-dependent cellular proliferation elicited by activation of 5-HT2ARs natively expressed in MCF-7 cells. Overall these findings indicate that the H452Y polymorphic variant of the 5-HT2AR displays selective disruption of its PLD signalling pathway. This may potentially play a role in the CNS dysfunction associated with the H452Y allele of the 5-HT2AR. [Copyright &y& Elsevier]

Background and Aims: An increasing number of patients with rectal cancer who respond well to neoadjuvant chemoradiotherapy (nCRT) are being considered for organ preservation programs. However, due to the lack of high-level evidence, the survival outcomes of the organ preservation programs are still full of controversy and uncertainty., Methods: To assess the effects of total mesorectal excision surgery (TME), watch-and-wait (W&W) and local excision (LE) on long-term outcomes after nCRT, we searched PubMed, Embase, and Web of Science for articles published between 1 January 2010, and 1 December 2023., Results: We found 7029 pieces of literature, of which 26 studies met the inclusion criteria, and recruited 2778 participants in the network meta-analysis. Risk of bias assessment showed that most included studies had a low risk of bias. Low-certainty evidence suggests that the TME group was significantly superior to all other interventions for the 2-year local regrowth rate. (W&W group [OR, 0.20; 95% CI, 0.12-0.35], LE group compared with TME group [3.00; 1.60 to 5.80]). There was no significant difference in the 2-year local regrowth rate between W&W and LE group (OR, 0.60; 95% CI, 0.32 to 1.20). There was high to moderate certainty evidence that at three years, the W&W group had a significant advantage in overall survival compared with the TME group (OR, 0.37; 95% CI, 0.09 to 0.95). After five years, no significant difference in overall survival was found between the three treatment modalities., Conclusions: We concluded that TME achieved the most significant reduction in 2-year local regrowth rates. However, the W&W strategy and LE demonstrated non-inferiority to TME in long-term survival outcomes., (Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. on Behalf of JBI.)

Background: Accurate evaluation of the response to preoperative treatment enables the provision of a more appropriate personalized therapeutic schedule for locally advanced rectal cancer (LARC), which remains an enormous challenge, especially neoadjuvant immunotherapy plus chemoradiotherapy (nICRT)., Methods: This prospective, multicenter cohort study enrolled patients with LARC from 6 centers who received nICRT. The dynamic variation in the gut microbiome during nICRT was evaluated. A species-level gut microbiome prediction (SPEED) model was developed and validated to predict the pathological complete response (pCR) to nICRT., Findings: A total of 50 patients were enrolled, 75 fecal samples were collected from 33 patients at different time points, and the pCR rate reached 42.4% (14/33). Lactobacillus and Eubacterium were observed to increase after nICRT. Additionally, significant differences in the gut microbiome were observed between responders and non-responders at baseline. Significantly higher abundances of Lachnospiraceae bacterium and Blautia wexlerae were found in responders, while Bacteroides, Prevotella, and Porphyromonas were found in non-responders. The SPEED model showcased a superior predictive performance with areas under the curve of 98.80% (95% confidence interval [CI]: 95.67%-100%) in the training cohort and 77.78% (95% CI: 65.42%-88.29%) in the validation cohort., Conclusions: Programmed death 1 (PD-1) blockade plus concurrent long-course CRT showed a favorable pCR rate and is well tolerated in microsatellite-stable (MSS)/mismatch repair-proficient (pMMR) patients with LARC. The SPEED model can be used to predict the pCR to nICRT based on the baseline gut microbiome with high robustness and accuracy, thereby assisting clinical physicians in providing individualized management for patients with LARC., Funding: This research was funded by the China National Natural Science Foundation (82202884)., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Metal complexes have received extensive attention in nonlinear optical (NLO) materials because of their advantages, such as shorter response times and more flexible structural properties. Density functional theory is used in investigating the geometric structures, electronic structures, charge centroid, and first hyperpolarizability (β tot ) of a series of selected 15 coordinated Ir(III) complexes. The substitute effect and one-electron redox process effects on the structures and properties of 15 coordinated Ir(III) complexes are considered. When the electron-withdrawing group is introduced into the ligand, the HOMO-LUMO energy gap decreases and the β tot value increases, positively correlating with the electron-withdrawing ability. The single electron redox process can also improve the NLO responses of complexes, especially the reduction process. The β tot value of complex 4 - is the largest, 2078 times higher than that of complex 4. The analysis shows that the variation of NLO responses of complexes is ascribed to the change of electronic structures and the charge transfer modes induced by the ligand modification and redox process, which are considered to be two effective methods in enhancing the NLO responses of 2-phenyl benzoquinoline Ir(III) complexes. This study aims to offer design insights into high-performance nonlinear optical materials.

Immune checkpoint therapy, such as programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) blockade, has achieved remarkable results in treating various tumors. However, most cancer patients show a low response rate to PD-1/PD-L1 blockade, especially those with microsatellite stable/mismatch repair-proficient colorectal cancer subtypes, which indicates an urgent need for new approaches to augment the efficacy of PD-1/PD-L1 blockade. Cholesterol metabolism, which involves generating multifunctional metabolites and essential membrane components, is also instrumental in tumor development. In recent years, inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9), a serine proteinase that regulates cholesterol metabolism, has been demonstrated to be a method enhancing the antitumor effect of PD-1/PD-L1 blockade to some extent. Mechanistically, PCSK9 inhibition can maintain the recycling of major histocompatibility protein class I, promote low-density lipoprotein receptor-mediated T-cell receptor recycling and signaling, and modulate the tumor microenvironment (TME) by affecting the infiltration and exclusion of immune cells. These mechanisms increase the quantity and enhance the antineoplastic effect of cytotoxic T lymphocyte, the main functional immune cells involved in anti-PD-1/PD-L1 immunotherapy, in the TME. Therefore, combining PCSK9 inhibition therapy with anti-PD-1/PD-L1 immunotherapy may provide a novel option for improving antitumor effects and may constitute a promising research direction. This review concentrates on the relationship between PCSK9 and cholesterol metabolism, systematically discusses how PCSK9 inhibition potentiates PD-1/PD-L1 blockade for cancer treatment, and highlights the research directions in this field., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Shengbo Sun et al.)

Colorectal cancer has the highest mortality rate of all digestive system diseases. Considering the debate about cytokines and biases that exist in traditional observational study designs, we performed a two-sample Mendelian randomization (MR) analysis to explore the association of circulating cytokines with CRC risk. In this study, we used cytokine genetic variants from a recently published genome-wide association study (GWAS) including 14,824 European-ancestry participants. Summary-level data for colorectal cancer were obtained from genome-wide association analyses of the FinnGen consortium. In addition, we conducted independent supplementary analyses using genetic variation data of colorectal cancer and cytokines from a large public GWAS in 2021. Among 91 circulating factors, we only found IL-12B to be significantly associated with CRC risk (odds ratio [OR]: 1.19; 95% confidence interval [CI]: 1.00-1.42; p = .046). We used 2021 data for analysis and found that higher Interleukin-12p70 levels (IL-12p70) were revealed to have a significant positive association with CRC risk (OR: 1.27; 95% CI: 1.13-1.43; p < 1.22 × 10 -3 ). Moreover, CRC was suggestively correlated with an elevated level of vascular endothelial growth factor (VEGF) (OR: 1.17; 95% CI: 1.02-1.35; p = .026), macrophage colony-stimulating factor (M-CSF) (OR: 0.85; 95% CI: 0.76-0.96; p = .005), IL-13 (OR: 1.15; 95% CI: 1.02-1.30; p = .028), IL-10 (OR: 1.23; 95% CI: 1.01-1.49; p = .037), and IL-7 (OR: 1.19; 95% CI: 1.02-1.39; p = .024). Our MR studies support that one cytokine IL-12 is significantly associated with CRC risk and that five cytokines VEGF, M-CSF, IL-13, IL-10, and IL-7 are associated with CRC risk., (© 2024 UICC.)

Introduction: Anastomotic leakage (AL) is defined as the failure of complete healing or disruption of the anastomosis subsequent to rectal cancer surgery, resulting in the extravasation of intestinal contents into the intra-abdominal or pelvic cavity. It is a serious complication of rectal cancer surgery, accounting for a considerable increase in morbidity and mortality. The use of fluorescence imaging technology in surgery allows surgeons to better evaluate blood perfusion. However, the conclusions of some existing studies are not consistent, so a consensus on whether the near-infrared indocyanine green (NIR-ICG) imaging system can reduce the incidence of AL is needed., Methods: This POSTER trial is designed as a multicentre, prospective, randomised controlled clinical study adhering to the "population, interventions, comparisons, outcomes (PICO)" principles. It is scheduled to take place from August 2019 to December 2024 across eight esteemed hospitals in China. The target population consists of patients diagnosed with rectal cancer through pathological confirmation, with tumours located≤10 cm from the anal verge, eligible for laparoscopic surgery. Enrolled patients will be randomly assigned to either the intervention group or the control group. The intervention group will receive intravenous injections of ICG twice, with intraoperative assessment of anastomotic blood flow using the near-infrared NIR-ICG system during total mesorectal excision (TME) surgery. Conversely, the control group will undergo conventional TME surgery without the use of the NIR-ICG system. A 30-day follow-up period postoperation will be conducted to monitor and evaluate occurrences of AL. The primary endpoint of this study is the incidence of AL within 30 days postsurgery in both groups. The primary outcome investigators will be blinded to the application of ICG angiography. Based on prior literature, we hypothesise an AL rate of 10.3% in the control group and 3% in the experimental group for this study. With a planned ratio of 2:1 between the number of cases in the experimental and control groups, and an expected 20% lost-to-follow-up rate, the initial estimated sample size for this study is 712, comprising 474 in the experimental group and 238 in the control group., Ethics and Dissemination: This study has been approved by Ethics committee of Beijing Friendship Hospital, Capital Medical University (approval number: 2019-P2-055-02). The results will be disseminated in major international conferences and peer-reviewed journals., Trial Registration Number: NCT04012645., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Density functional theory studies on the geometric and electronic structures, UV-vis absorption spectra, and second-order nonlinear optical (NLO) properties of four-coordinate Pt(II) bis-acetylide complexes, cis -[Pt(CN t Bu)(ADC)(CCR) 2 ] , have been employed. The effects of ligand variation and the single electron redox process on the structures and NLO response of complexes have also been investigated. It shows that the variations of the ligand and electron have little effect on the geometries of the complexes, but there is a significant effect on their electronic structures and NLO responses. The introduction of a single -NO 2 group in acetylide ligands increases the first hyperpolarizability of complex 12 times, while one electron lost in five complexes enhances the first hyperpolarizability 496 times at the most. Both methods are considered effective ways for improving the NLO response of Pt(II) bis-acetylide complexes. Based on the analysis of the electronic and optical properties of fifteen studied complexes, the increase of NLO response is mainly ascribed to strong oscillator strengths, lower electron transition energy, and well-directed effective charge transfer. This work reveals some underlying relationships between the NLO responses and electronic structures of complexes, which is helpful for the design and synthesis of high-performance NLO materials of Pt(II) bis-acetylide complexes.

To investigate the umami mechanisms and characteristics of soy sauce flavor peptides, four fractions from natural brewed soy sauce were separated using ultrafiltration and Sephadex G-15 gel filtration chromatography. Sensory and ligand-receptor interaction tests showed that the umami strengths of the fractions were related as follows: U1 > U2, G3 > G2, and G3 > U1. Peptide identification revealed that the < 550-Da peptides might be the major contributors to the umami taste of U1 and G3. The higher umami strength of G3 might be attributable to its higher content of umami peptides. G3's concentration-relative umami intensity curve was plotted using a two-alternative forced choice test. It was also revealed that less sourness, higher saltiness and cool (4 ℃) and hot (50 ℃) serving conditions were conductive to the umami perception of G3. The results could provide a reference for the application of soy-sauce flavor peptides in food., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Programmed cell death protein (PD-1) is an important immunosuppressive molecule, which can inhibit interaction between PD-1 and its ligand PD-L1, further enhancing the T cell response and anti-tumor activity, which is called immune checkpoint blockade. Immunotherapy, represented by immune checkpoint inhibitors, has opened up a new era of tumor treatment and is gradually being applied to colorectal cancer recently. Immunotherapy was reported could achieve a high objective response rate (ORR) for colorectal cancer with high microsatellite instability (MSI), thus opening up a new era of colorectal cancer immunotherapy. Along with the increasing use of PD1 drugs in colorectal cancer, we should pay more attention to the adverse effects of these immune drugs while seeing the hope. Immune-related adverse events (irAEs) caused by immune activation and immune homeostasis during anti-PD-1/PD-L1 therapy can affect multi-organ and even be fatal in serious cases. Therefore, understanding irAEs is essential for their early detection and appropriate management. In this article, we review the irAEs that occur during the treatment of colorectal cancer patients with PD-1/PD-L1 drugs, analyze the current controversies and challenges, and point out future directions that should be explored, including exploring efficacy predictive markers and optimizing the paradigm of individualized immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sun, Meng, Zhang, Gao, Wei, Zhang and Zhang.)

Neuropathic pain (NP) induced by spinal cord injury (SCI) often causes long-term disturbance for patients, but the mechanisms behind remains unclear. Here, our study showed SCI-induced ectopic expression of Nav1.7 in abundant neurons located in deep and superficial laminae layers of the spinal dorsal horn (SDH) and upregulation of Nav1.7 expression in dorsal root ganglion (DRG) neurons in mice. Pharmacologic studies demonstrated that the efficacy of the blood-brain-barrier (BBB) permeable Nav1.7 inhibitor GNE-0439 for attenuation of NP in SCI mice was significantly better than that of the BBB non-permeable Nav1.7 inhibitor PF-05089771. Moreover, more than 20% of Nav1.7-expressing SDH neurons in SCI mice were activated to express FOS when there were no external stimuli, suggesting that the ectopic expression of Nav1.7 made SDH neurons hypersensitive and Nav1.7-expressing SDH neurons participated in central sensitization and in spontaneous pain and/or walking-evoked mechanical pain. Further investigation showed that NGF, a strong activator of Nav1.7 expression, and its downstream JUN were upregulated after SCI in SDH neurons with similar distribution patterns and in DRG neurons too. In conclusion, our findings showed that the upregulation of Nav1.7 was induced by SCI in both SDH and DRG neurons through increased expression of NGF/JUN, and the inhibition of Nav1.7 in both peripheral and spinal neurons alleviated mechanical pain in SCI mice. These data suggest that BBB permeable Nav1.7 blockers might relieve NP in patients with SCI and that blocking the upregulation of Nav1.7 in the early stage of SCI via selective inhibition of the downstream signaling pathways of NGF or Nav1.7-targeted RNA drugs could be a strategy for therapy of SCI-induced NP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Fu, Sun, Zhu, Xia, Wen, Xia, Yu, Xu and Peng.)

Purpose: Surgical complications following laparoscopic rectal cancer surgery remain a major clinical problem. The prognostic nutritional index (PNI) is reportedly associated with postoperative outcomes. We aimed to evaluate the correlation between PNI and short-term surgical complications in patients with rectal cancer after laparoscopic surgery., Methods: The prospective clinical data of 225 patients with rectal cancer receiving laparoscopic surgery between January 2021 and April 2022 were retrospectively analyzed. The cut-off values and diagnostic accuracy of PNI preoperatively and on postoperative day (POD) 1 were determined using receiver operating characteristic (ROC) curves. Univariate and multivariate analyses were performed to identify clinical characteristics and risk factors for surgical complications., Results: In total, 81 (36.0%) patients developed surgical complications. The optimal cut-off value for preoperative PNI was 40.15, and that for PNI on POD 1 was 35.28. The DeLong test found no statistically between-group difference in the area under the ROC curve ( P  = 0.598). Multivariate analysis identified that a preoperative PNI ≤40.15 [odds ratio (OR): 2.856, 95% confidence interval (CI): 1.287-6.341, P  = 0.010] and PNI on POD 1 ≤35.28 (OR: 2.773, 95% CI: 1.533-5.016, P  = 0.001) were independent risk factors for surgical complications. Patients with a preoperative PNI ≤40.15 or PNI on POD 1 ≤35.28 were more likely to have surgical complications after laparoscopic surgery for rectal cancer (61.1% vs. 31.2%, P  = 0.001; 53.0% vs. 28.9%, P  = 0.001)., Conclusion: Preoperative and POD 1 PNI were independent predictors of short-term surgical complications after laparoscopic surgery for rectal cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Xu, Meng, Yang, Li, Gao, Sun, Zhang, Wei, Wu, Yao and Zhang.)

Immunotherapies, especially the programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) inhibitors, have revolutionized the therapeutic strategies of various cancers. As for colorectal cancer (CRC), the current clinical application of PD-1/PD-L1 inhibitors are mainly used according to the mutation pattern, which is categorized into deficient mismatch repair (dMMR)/high levels of microsatellite instability (MSI-H) and proficient mismatch repair (pMMR), or non-high levels of microsatellite instability (non-MSI-H). PD-1/PD-L1 inhibitors have been proven to have favorable outcomes against dMMR/MSI-H CRC because of more T-cell infiltration into tumor tissues. Nevertheless, the effectiveness of PD-1/PD-L1 inhibitors in pMMR/non-MSI-H CRC is still uncertain. Because of the quite-lower proportion of dMMR/MSI-H in CRC, PD-1/PD-L1 inhibitors have been reported to combine with other antitumor treatments including chemotherapy, radiotherapy, and targeted therapy for better therapeutic effect in recent clinical trials. Neoadjuvant therapy, mainly including chemotherapy and radiotherapy, not only can reduce clinical stage but also benefit from local control, which can improve clinical symptoms and the quality of life. Adding immunotherapy into neoadjuvant therapy may change the treatment strategy of primary resectable or some metastatic CRC. In this review, we focus on the development of neoadjuvant anti-PD-1/PD-L1 therapy and discuss the future perspectives in CRC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Wu, Zhang, Gao, Meng, Liu, Wei, Sun, Wei, Bai, Yao and Zhang.)

Abstract: Primary cutaneous lymphoma occurring at the site of lymphedema is a rare complication. A total of 13 cases of primary cutaneous lymphoma associated with chronic lymphedema have been reported in international studies. We reported a case of cutaneous diffuse large B-cell lymphoma (DLBCL) (leg type) secondary to chronic lymphedema of the lower limbs. Histopathology showed hyperkeratosis of epidermis, acanthosis, and significant edema in the superficial dermis, with diffuse mononuclear infiltration in the dermis. Immunohistochemical studies revealed the expression of CD5, CD20, Pax-5, Bcl-2, Bcl-6, MUM-1, c-myc, and Ki-67. Therefore, the diagnosis of cutaneous DLBCL (leg type) was made. The study further confirmed the association between lymphoma and lymphedema. Especially, it showed CD5 expression. CD5-positive DLBCLs is a specific subgroup of DLBCLs, only approximately 10% of DLBCLs express CD5., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Deoxycytidine monophosphate deaminase (dCMP deaminase, DCD) is crucial to the production of dTTP needed for DNA replication and damage repair. However, the effect of DCD deficiency and its molecular mechanism are poorly understood in plants. Here, we isolated and characterized a rice albinic leaf and growth retardation (alr) mutant that is manifested by albinic leaves, dwarf stature and necrotic lesions. Map-based cloning and complementation revealed that ALR encodes a DCD protein. OsDCD was expressed ubiquitously in all tissues. Enzyme activity assays showed that OsDCD catalyses conversion of dCMP to dUMP, and the ΔDCD protein in the alr mutant is a loss-of-function protein that lacks binding ability. We report that alr plants have typical DCD-mediated imbalanced dNTP pools with decreased dTTP; exogenous dTTP recovers the wild-type phenotype. A comet assay and Trypan Blue staining showed that OsDCD deficiency causes accumulation of DNA damage in the alr mutant, sometimes leading to cell apoptosis. Moreover, OsDCD deficiency triggered cell cycle checkpoints and arrested cell progression at the G1/S-phase. The expression of nuclear and plastid genome replication genes was down-regulated under decreased dTTP, and together with decreased cell proliferation and defective chloroplast development in the alr mutant this demonstrated the molecular and physiological roles of DCD-mediated dNTP pool balance in plant development., (© The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)