Multidisciplinary management of ulcerative colitis complicated by immune checkpoint inhibitor-associated colitis with life-threatening gastrointestinal hemorrhage: A case report.

BACKGROUND: Programmed cell death 1 (PD-1) inhibitors are immune checkpoint inhibitors (ICI) that have demonstrated significant efficacy in treating various advanced malignant tumors. While most patients tolerate treatment well, several adverse drug reactions, such as fatigue, myelosuppression, and ICI-associated colitis, have been reported. CASE SUMMARY: This case involved a 57-year-old male patient with ulcerative colitis complicated by hepatocarcinoma who underwent treatment with tirelizumab (a PD-1 inhibitor) for six months. The treatment led to repeated life-threatening lower gastrointestinal hemorrhage. The patient received infliximab, vedolizumab, and other salvage procedures but ultimately required subtotal colectomy due to uncontrollable massive lower gastrointestinal bleeding. Currently, postoperative gastrointestinal bleeding has stopped, the patient's stool has turned yellow, and his full blood cell count has returned to normal. CONCLUSION: This case highlights the necessity of early identification, timely and adequate treatment of ICI-related colitis, and rapid escalation to achieve the goal of improving prognosis.

Asynchronous Control of 2-D Markov Jump Roesser Systems With Nonideal Transition Probabilities.

This article intends to study the asynchronous control problem for 2-D Markov jump systems (MJSs) with nonideal transition probabilities (TPs) under the Roesser model. Two practical considerations motivate the current work. First, considering that the system mode cannot always be observed accurately, a hidden Markov model (HMM) is adopted to describe the relationship between the mismatched modes. Second, considering that the TPs information related to the Markov process and the observation process is difficult to obtain, the nonideal TPs (unknown or uncertain) are simultaneously considered on the two processes. Under the considerations, several new sufficient conditions are developed for concerned closed-loop 2-D MJSs with nonideal TPs, by which the asymptotic mean square stability is ensured with an H∞ performance index. A nonconservative separation strategy is utilized to decouple the system mode TPs and the observation TPs to facilitate the analysis of nonideal TPs. An unified LMI-based condition is finally developed for the concerned closed-loop 2-D MJSs with/without nonideal TPs, showing more satisfactory conservatism than that in the literature. In the end, we present two examples to validate the superiority of the proposed design method.

Mitochondrial complex I promotes kidney cancer metastasis.

Most kidney cancers are metabolically dysfunctional1-4, but how this dysfunction affects cancer progression in humans is unknown. We infused 13C-labelled nutrients in over 80 patients with kidney cancer during surgical tumour resection. Labelling from [U-13C]glucose varies across subtypes, indicating that the kidney environment alone cannot account for all tumour metabolic reprogramming. Compared with the adjacent kidney, clear cell renal cell carcinomas (ccRCCs) display suppressed labelling of tricarboxylic acid (TCA) cycle intermediates in vivo and in ex vivo organotypic cultures, indicating that suppressed labelling is tissue intrinsic. [1,2-13C]acetate and [U-13C]glutamine infusions in patients, coupled with measurements of respiration in isolated human kidney and tumour mitochondria, reveal lower electron transport chain activity in ccRCCs that contributes to decreased oxidative and enhanced reductive TCA cycle labelling. However, ccRCC metastases unexpectedly have enhanced TCA cycle labelling compared with that of primary ccRCCs, indicating a divergent metabolic program during metastasis in patients. In mice, stimulating respiration or NADH recycling in kidney cancer cells is sufficient to promote metastasis, whereas inhibiting electron transport chain complex I decreases metastasis. These findings in humans and mice indicate that metabolic properties and liabilities evolve during kidney cancer progression, and that mitochondrial function is limiting for metastasis but not growth at the original site.

AGFG1 increases cholesterol biosynthesis by disrupting intracellular cholesterol homeostasis to promote PDAC progression.

PURPOSE: Cholesterol metabolism reprograming has been acknowledged as a novel feature of cancers. Pancreatic ductal adenocarcinoma (PDAC) is a cancer with a high demand of cholesterol for rapid growth. The underlying mechanism of how cholesterol metabolism homestasis are disturbed in PDAC is explored. EXPERIMENTAL DESIGN: The relevance between PDAC and cholesterol was confirmed in TCGA database. The expression and clinical association were discovered in TCGA and GEO datasets. Knockdown and overexpression of AGFG1 was adopted to perform function studies. RNA sequencing, cholesterol detection, transmission electron microscope, co-immunoprecipitation, and immunofluorescence et al. were utilized to reveal the underlying mechanism. RESULTS: AGFG1 was identified as one gene positively correlated with cholesterol metabolism in PDAC as revealed by bioinformatics analysis. AGFG1 expression was then found associated with poor prognosis in PDAC. AGFG1 knockdown led to decreased proliferation of tumor cells both in vitro and in vivo. By RNA sequencing, we found AGFG1 upregulated expression leads to enhanced intracellular cholesterol biosynthesis. AGFG1 knockdown suppressed cholesterol biosynthesis and an accumulation of cholesterol in the ER. Mechanistically, we confirmed that AGFG1 interacted with CAV1 to relocate cholesterol for the proceeding of cholesterol biosynthesis, therefore causing disorders in intracellular cholesterol metabolism. CONCLUSIONS: Our study demonstrates the tumor-promoting role of AGFG1 by disturbing cholesterol metabolism homestasis in PDAC. Our study has present a new perspective on cancer therapeutic approach based on cholerstrol metabolism in PDAC.

Genome-Wide Identification and Expression Pattern Analysis of the WNK Gene Family in Apple under Abiotic Stress and Colletotrichum siamense Infection.

With-no-lysine kinase (WNK) is a unique serine/threonine kinase family member. WNK differs from other protein kinases by not having a standard lysine in subdomain II of the universally preserved kinase catalytic region. Conversely, the amino acid lysine located in subdomain I plays a crucial role in its phosphorylation. The WNK family has been reported to regulate Arabidopsis flowering, circadian rhythm, and abiotic stress. Eighteen members of the WNK gene family were discovered in apples in this research, and they were primarily grouped into five categories on the phylogenetic tree. Conserved domains and motifs also confirmed their identity as members of the WNK family. Promoter cis-acting element analysis indicated their potential role in responses to both abiotic stress and phytohormones. Furthermore, qRT-PCR analysis showed that the expression of MdWNK family genes was stimulated to different extents by Colletotrichum siamense, NaCl, mannitol, ABA, JA, and SA, with Colletotrichum siamense being the most prominent stimulant. MdWNK family genes were expressed across all apple tissues, with young fruits showing the greatest expression and roots showing the least expression. The research offered detailed insights into the MdWNK gene family, serving as a crucial basis for investigating the biological roles of MdWNK genes.

Early colorectal cancer screening-no time to lose.

In this editorial, we comment on the article entitled "Stage at diagnosis of colorectal cancer through diagnostic route: Who should be screened?" by Agatsuma et al. Colorectal cancer (CRC) is emerging as an important health issue as its incidence continues to rise globally, adversely affecting the quality of life. Although the public has become more aware of CRC prevention, most patients lack screening awareness. Some poor lifestyle practices can lead to CRC and symptoms can appear in the early stages of CRC. However, due to the lack of awareness of the disease, most of the CRC patients are diagnosed already at an advanced stage and have a poor prognosis.

Emergency rescue of a patient with hemorrhagic shock caused by superior mesenteric artery rupture: A case report.

BACKGROUND: Superior mesenteric artery (SMA) injuries rarely occur during blunt abdominal injuries, with an incidence of < 1%. The clinical manifestations mainly include abdominal hemorrhage and peritoneal irritation, which progress rapidly and are easily misdiagnosed. Quick and accurate diagnosis and timely effective treatment are greatly significant in managing emergent cases. This report describes emergency rescue by a multidisciplinary team of a patient with hemorrhagic shock caused by SMA rupture. CASE SUMMARY: A 55-year-old man with hemorrhagic shock presented with SMA rupture. On admission, he showed extremely unstable vital signs and was unconscious with a laceration on his head, heart rate of 143 beats/min, shallow and fast breathing (frequency > 35 beats/min), and blood pressure as low as 20/10 mmHg (1 mmHg = 0.133 kPa). Computed tomography revealed abdominal and pelvic hematocele effusion, suggesting active bleeding. The patient was suspected of partial rupture of the distal SMA branch. The patient underwent emergency mesenteric artery ligation, scalp suture, and liver laceration closure. In view of conditions with acute onset, rapid progression, and high bleeding volume, key points of nursing were conducted, including activating emergency protocol, opening of the green channel, and arranging relevant examinations with various medical staff for quick diagnosis. The seamless collaboration of the multidisciplinary team helped shorten the preoperative preparation time. Emergency laparotomy exploration and mesenteric artery ligation were performed to mitigate hemorrhagic shock while establishing efficient venous accesses and closely monitoring the patient's condition to ensure hemodynamic stability. Strict measures were taken to avoid intraoperative hypothermia and infection. CONCLUSION: After 3.5 h of emergency rescue and medical care, bleeding was successfully controlled, and the patient's condition was stabilized. Subsequently, the patient was transferred to the intensive care unit for continuous monitoring and treatment. On the sixth day, the patient was weaned off the ventilator, extubated, and relocated to a specialized ward. Through diligent medical intervention and attentive nursing, the patient made a full recovery and was discharged on day 22. The follow-up visit confirmed the patient's successful recovery.

Percutaneous ablation for adrenal metastasis from non-small-cell lung cancer: comparison between cryoablation and microwave ablation.

Introduction: While cryoablation (CA) and microwave ablation (MWA) have both been implemented as approaches to the treatment of adrenal metastasis (AM), the outcomes associated with these two therapeutic strategies remain unclear. Aim: To compare the safety and efficacy of CA and MWA as treatments for AM in patients with non-small-cell lung cancer (NSCLC). Material and methods: Consecutive patients with AM secondary to NSCLC from January 2015 to December 2020 underwent CA or MWA. Treatment-related outcomes and complications were retrospectively compared between these groups. Results: In total, 68 NSCLC patients with isolated AM were enrolled in this study, of whom 35 and 33 underwent treatment with CA and MWA, respectively. Primary complete ablation rates in the CA and MWA groups were 91.4% (32/35) and 93.9% (31/33) respectively (p = 1.000), while a 100% secondary complete ablation rate was observed for both groups. Hypertensive crisis incidence affected 11.4% (4/35) and 9.1% (3/33) of patients in the CA and MWA groups (p = 1.000), respectively, while 8 (22.9%) and 8 (24.2%) patients in these corresponding groups experienced local progression after ablation that was detected during the follow-up period (p = 0.893). Patients in the CA and MWA groups exhibited a median progression-free survival of 18 and 22 months, respectively (p = 0.411), while the corresponding median overall survival of patients in these groups was 25 and 29 months (p = 0.786). Conclusions: CT-guided CA and MWA appear to exhibit similar safety and efficacy profiles when employed to treat isolated AM in NSCLC patients.

Measurement of the distance between tumor micro-foci and gross tumor in rectal cancer pathological specimens: implication on margin distance of clinical target volume treated with high-dose radiotherapy for rectal cancer.

PURPOSE: To measure the micro-foci distance away from gross tumor and to provide reference to create the clinical target volume (CTV) margin for boost radiotherapy in rectal adenocarcinoma. METHODS: Twenty-eight rectal cancer surgical specimens of only total mesorectal excision were collected. The pathological specimens were retrospectively measured, and the nearest distance between the tumor micro-foci and gross tumor was microscopically measured. The "in vivo-in vitro" retraction factor was calculated as the ratio of the deepest thickness laterally and the vertical height superior/inferiorly of the rectal tumor measured in MRI and those measured in immediate pathological specimens. The retraction factor during pathological specimen processing was calculated as the distance ratio before and after dehydration in the lateral, superior, and inferior sides by the "knot marking method." The distances of tumor micro-foci were individually corrected with these two retraction factors. RESULTS: The mean "in vivo-in vitro" tumor retraction factors were 0.913 peripherally and 0.920 superior/inferiorly. The mean tumor specimen processing retraction factors were 0.804 peripherally, 0.815 inferiorly, and 0.789 superiorly. Of 28 patients, 14 cases (50.0%) had 24 lateral micro-foci, 8 cases (28.6%) had 13 inferior micro-foci, and 7 cases (25.0%) had 19 superior micro-foci. The 95th percentiles of the micro-foci distance for 28 patients were 6.44 mm (peripheral), 5.54 mm (inferior), and 5.42 mm (superior) after retraction correction. CONCLUSION: The micro-foci distances of 95% of rectal adenocarcinoma patients examined were within 6.44 mm peripherally, 5.54 mm inferiorly, and 5.42 mm superiorly. These findings provide reference to set the boost radiotherapy CTV margin for rectal cancer.

Lomitapide repurposing for treatment of malignancies: A promising direction.

The development of novel drugs from basic science to clinical practice requires several years, much effort, and cost. Drug repurposing can promote the utilization of clinical drugs in cancer therapy. Recent studies have shown the potential effects of lomitapide on treating malignancies, which is currently used for the treatment of familial hypercholesterolemia. We systematically review possible functions and mechanisms of lomitapide as an anti-tumor compound, regarding the aspects of apoptosis, autophagy, and metabolism of tumor cells, to support repurposing lomitapide for the clinical treatment of tumors.

Receptor tyrosine kinase-like orphan receptor 1: A novel antitumor target in gastrointestinal cancers.

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a member of the type I receptor tyrosine kinase family. ROR1 is pivotal in embryonic development and cancer, and serves as a biomarker and therapeutic target. It has soluble and membrane-bound subtypes, with the latter highly expressed in tumors. ROR1 is conserved throughout evolution and may play a role in the development of gastrointestinal cancer through multiple signaling pathways and molecular mechanisms. Studies suggest that overexpression of ROR1 may increase tumor invasiveness and metastasis. Additionally, ROR1 may regulate the cell cycle, stem cell characteristics, and interact with other signaling pathways to affect cancer progression. This review explores the structure, expression and role of ROR1 in the development of gastrointestinal cancers. It discusses current antitumor strategies, outlining challenges and prospects for treatment.

Eight new spider species of Belisana Thorell, 1898 (Araneae, Pholcidae), with an updated overview of Belisana species from Yunnan, China.

In this study, eight new species are described from the subtropical parts of Yunnan Province in southwestern China: Belisanahonghe Zhang, Li & Yao, sp. nov. (♂♀), B.jiuxiang Zhang, Li & Yao, sp. nov. (♂♀), B.lincang Zhang, Li & Yao, sp. nov. (♂♀), B.luxi Zhang, Li & Yao, sp. nov. (♂♀), B.tengchong Zhang, Li & Yao, sp. nov. (♂♀), B.tongi Zhang, Li & Yao, sp. nov. (♂♀), B.yongsheng Zhang, Li & Yao, sp. nov. (♂), and B.yunnan Zhang, Li & Yao, sp. nov. (♂♀). They add up to a total of 31 Belisana species from Yunnan in an updated list provided in this paper.

Electron transport chain inhibition increases cellular dependence on purine transport and salvage.

Mitochondria house many metabolic pathways required for homeostasis and growth. To explore how human cells respond to mitochondrial dysfunction, we performed metabolomics in fibroblasts from patients with various mitochondrial disorders and cancer cells with electron transport chain (ETC) blockade. These analyses revealed extensive perturbations in purine metabolism, and stable isotope tracing demonstrated that ETC defects suppress de novo purine synthesis while enhancing purine salvage. In human lung cancer, tumors with markers of low oxidative mitochondrial metabolism exhibit enhanced expression of the salvage enzyme hypoxanthine phosphoribosyl transferase 1 (HPRT1) and high levels of the HPRT1 product inosine monophosphate. Mechanistically, ETC blockade activates the pentose phosphate pathway, providing phosphoribosyl diphosphate to drive purine salvage supplied by uptake of extracellular bases. Blocking HPRT1 sensitizes cancer cells to ETC inhibition. These findings demonstrate how cells remodel purine metabolism upon ETC blockade and uncover a new metabolic vulnerability in tumors with low respiration.

Hybrid integrated optical chaos circuits with optoelectronic feedback.

A chip-scale chaotic laser system with optoelectronic delayed feedback is proposed and analyzed by numerical simulation. This chip eliminates the need for bulky delay components such as long optical fibers, free propagation and external cavities, relying solely on internal devices and waveguides to achieve feedback delay. This approach simplifies integration, maintaining a compact chip size. According to the results, the chip-scale system exhibits rich dynamics, including periodicity, quasi-periodicity, and chaotic states. Chaos resembling Gaussian white noise is achieved with picosecond-level delay time, highlighting the complexity of chip-scale signals. Furthermore, time delay signature (TDS) concealment is enhanced with a short delay comparable to the inverse bandwidth τ, albeit at a cost of sacrificing chaotic signal complexity. Applying the photonic integrated circuits to practical applications, 1 Gbps back-to-back communication transmission is feasible. Results demonstrate low bit error rates (BERs) for authorizers (<10-6) and high BERs for eavesdroppers (>10-2), ensuring communication confidentiality and chaotic synchronization. Lastly, preliminary experiments validate the feasibility. Our theoretical work has demonstrated the feasibility of hybrid integrated optical chaos circuits with optoelectronic feedback based on photonic wire bonding, which can provide a stable and flexible integrated chaos source.

Role of deubiquitinase USP47 in cardiac function alleviation and anti-inflammatory immunity after myocardial infarction by regulating NLRP3 inflammasome-mediated pyroptotic signal pathways.

Myocardial infarction (MI) is an event of heart attack due to the formation of plaques in the interior walls of the arteries. This study is conducted to explore the role of ubiquitin-specific peptidase 47 (USP47) in cardiac function and inflammatory immunity. MI mouse models were established, followed by an appraisal of cardiac functions, infarct size, pathological changes, and USP47 and NLRP3 levels. MI cell models were established in HL-1 cells using anoxia. Levels of cardiac function-associated proteins, USP7, interferon regulatory factor 1 (IRF1), platelet factor-4 (CXCL4), pyroptotic factors, and neutrophil extracellular traps (NETs) were determined. The bindings of IRF1 to USP47 and the CXCL4 promoter and the ubiquitination of IRF1 were analyzed. USP47 was upregulated in myocardial tissues of MI mice. USP47 inhibition alleviated cardiac functions, and decreased infarct size, pro-inflammatory cytokines, NETs, NLRP3, and pyroptosis. The ubiquitination and expression levels of IRF1 were increased by silencing USP47, and IRF1 bound to the CXCL4 promoter to promote CXCL4. Overexpression of IRF1 or CXCL4 in vitro and injection of Nigericin in vivo reversed the effect of silencing USP47 on alleviating pyroptosis and cardiac functions. Collectively, USP47 stabilized IRF1 and promoted CXCL4, further promoting pyroptosis, impairing cardiac functions, and aggravating immune inflammation through NLRP3 pathways.

[Accuracy and clinical efficacy of robot-assisted transiliac-transsacral screw placement for posterior pelvic ring fractures].

OBJECTIVE: To explore accuracy and clinical effect of robot-assisted implantation of sacroiliac penetrating screw in orthopedic surgery for posterior pelvic ring fracture. METHODS: The clinical data of 24 patients with posterior pelvic ring fracture treated with robot-assisted sacroiliac penetration screws from August 2022 to August 2023 were retrospectively analyzed, including 10 males and 14 females; aged from 21 to 73 years old with an average of (49.29±14.48) years old;according to Tile pelvic fractures, 13 patients were type B and 11 were type C. The effect of screw placement was evaluated according to Gras criteria based on postoperative CT scan results. At the final follow-up, fracture healing was evaluated according to Matta score, and functional recovery was evaluated by Majeed score. RESULTS: All patients were followed up for 3 to 13 months with an average of (6.00±3.28) months. Totally 36 sacroiliac penetrating screws, 18 S1 penetrating screws, 18 S2 penetrating screws were inserted, a total of 29 were excellent and 7 good according to Gras standard. Screw adjustment times was 0.00 (0.00, 0.75) times. At the final follow-up, Matta score was excellent in 18 patients, 5 good and 1 moderate, and the maximum displacement distance was 2.55 (0.00, 5.65) mm. Majeed score was 84.37±8.38, 15 patients were excellent, 7 good and 2 moderate. CONCLUSION: Robot could accurately and safely assist in the placement of sacroiliac joint screws for the treatment of posterior pelvic ring fractures, and promote postoperative functional recovery of patients.

Increasing Multienzyme Cascade Efficiency and Stability of MOF via Partitioning Immobilization.

Enhancing the stability of multienzyme cascade reactions in metal-organic frameworks (MOFs) is a challenging task in the fields of biotechnology and chemistry. However, addressing this challenge could yield far-reaching benefits across the application range in the biomedical, food, and environmental sectors. In this study, multienzyme partitioning immobilization that sequentially immobilizes cascade enzymes with hierarchical MOFs is proposed to reduce substrate diffusion resistance. Conversion results of ginsenosides indicate that this strategy improves the cascade efficiency up to 1.26 times. The substrate diffusion model is used to investigate the dual-interenzyme mass transfer behavior of substrates in the restricted domain space and evaluate the substrate channeling effect under partitioning immobilization. Molecular docking and kinetic simulations reveal that the MOFs effectively limit the conformational changes of cascade enzymes at high temperatures and in organic solvents while maintaining a large pocket of active centers. This phenomenon increased efficient substrate docking to the enzyme molecules, further optimizing cascade efficiency. The results of the immobilization of GOX and horseradish peroxidase as model enzymes indicate that the partitioned MOF immobilization strategy could be used for universal adaptation of cascade enzymes.

Amelioration activity of the high bioaccessible chrysanthemum (Gongju) phenolics on alcohol-induced oxidative injury in AML-12 cells.

The main bioavailable phenolics from of Gongju (GJ) and their mechanism for hepato-protection remain unclear. To select the GJ phenolics with high bioavailability, chrysanthemum digestion and Caco-2 cells were used and their hepato-protective potential were examined by using AML-12 cells. The digestive recovery and small intestinal transit rate of the main phenolic compounds ranged from 28.52 to 69.53% and 6.57% âˆ¼ 15.50%, respectively. Among them, chlorogenic acid, 3,5-dicaffeoylquinic acid, and 1,5-dicaffeoylquinic acid, showed higher small intestinal transit rates and digestive recoveries. Furthermore, we found that by increasing intracellular Catalase (CAT) and Superoxide dismutase (SOD) viability and lowering Malondialdehyde (MDA) level (P < 0.05), 3,5-dicaffeoylquinic acid significantly mitigated the oxidative damage of AML-12 liver cells more than the other two phenolics. Our results demonstrated that 3,5-dicaffeoylquninic acid was the primary phenolic compounds in GJ that effectively reduced liver damage, providing a theoretical basis for the development of GJ as a potentially useful resource for hepatoprotective diet.

Abnormal Degraded Tapetum 1 (ADT1) is required for tapetal cell death and pollen development in rice.

The timely degradation of tapetum, the innermost somatic anther cell layer in flowering plants, is critical for pollen development. Although several genes involved in tapetum development have been characterized, the molecular mechanisms underlying tapetum degeneration remain elusive. Here, we showed that mutation in Abnormal Degraded Tapetum 1 (ADT1) resulted in overaccumulation of Reactive Oxygen Species (ROS) and abnormal anther development, causing earlier tapetum Programmed Cell Death (PCD) and pollen abortion. ADT1 encodes a nuclear membrane localized protein, which is strongly expressed in the developing microspores and tapetal cells during early anther development. Moreover, ADT1 could interact with metallothionein MT2b, which was related to ROS scavenging and cell death regulation. These findings indicate that ADT1 is required for proper timing of tapetum PCD by regulating ROS homeostasis, expanding our understanding of the regulatory network of male reproductive development in rice.

High-integrity Pueraria montana var. lobata genome and population analysis revealed the genetic diversity of Pueraria genus.

Pueraria montana var. lobata (P. lobata) is a traditional medicinal plant belonging to the Pueraria genus of Fabaceae family. Pueraria montana var. thomsonii (P. thomsonii) and Pueraria montana var. montana (P. montana) are its related species. However, evolutionary history of the Pueraria genus is still largely unknown. Here, a high-integrity, chromosome-level genome of P. lobata and an improved genome of P. thomsonii were reported. It found evidence for an ancient whole-genome triplication and a recent whole-genome duplication shared with Fabaceae in three Pueraria species. Population genomics of 121 Pueraria accessions demonstrated that P. lobata populations had substantially higher genetic diversity, and P. thomsonii was probably derived from P. lobata by domestication as a subspecies. Selection sweep analysis identified candidate genes in P. thomsonii populations associated with the synthesis of auxin and gibberellin, which potentially play a role in the expansion and starch accumulation of tubers in P. thomsonii. Overall, the findings provide new insights into the evolutionary and domestication history of the Pueraria genome and offer a valuable genomic resource for the genetic improvement of these species.