Intrarenal pressure detection during flexible ureteroscopy with fiber optic pressure sensor system in porcine model.

To validate the feasibility of a fiber-optic pressure sensor-based pressure measurement device for monitoring intrarenal pressure and to analyze the effects of ureteral acess sheath (UAS) type, surgical location, perfusion flow rate, and measurement location on intrarenal pressure (IRP). The measurement deviations and response times to transient pressure changes were compared between a fiber-optic pressure sensing device and a urodynamic device IRP in an in vitro porcine kidney and in a water tank. Finally, pressure measurements were performed in anesthetized female pigs using fiber-optic pressure sensing device with different UAS, different perfusion flow rates, and different surgical positions at different renal calyces and ureteropelvic junctions (UPJ). According to our operation, the result is fiber optic pressure sensing devices are highly accurate and sensitive. Under the same conditions, IRP varied among different renal calyces and UPJ (P < 0.05). IRP was lowest at 50 ml/min and highest at 150 ml/min (P < 0.05). Surgical position had a significant effect on IRP (P < 0.05). 12/14 Fr UAS had a lower IRP than 11/13 Fr UAS. Therefore fiber optic pressure sensing devices are more advantageous for IRP measurements. In ureteroscopy, the type of ureteral sheath, the surgical position, the perfusion flow rate, and the location of the measurement all affect the intrarenal pressure value.

Memory/active T cell activation is associated with immunotherapeutic response in fumarate hydratase-deficient renal cell carcinoma.

PURPOSE: Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare and lethal subtype of kidney cancer. However, the optimal treatments and molecular correlates of benefits for FH-deficient RCC are currently lacking. EXPERIMENTAL DESIGN: A total of 91 patients with FH-deficient RCC from 15 medical centers between 2009 and 2022 were enrolled in this study. Genomic and bulk RNA sequencing (RNA-seq) were performed on 88 and 45 untreated FH-deficient RCCs, respectively. Single-cell RNA-seq was performed to identify biomarkers for treatment response. Main outcomes included disease-free survival (DFS) for localized patients, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) for metastatic patients. RESULTS: In the localized setting, we found that a cell cycle progression signature enabled to predict disease progression. In the metastatic setting, first-line immune checkpoint inhibitor plus tyrosine kinase inhibitor (ICI+TKI) combination therapy showed satisfactory safety and was associated with a higher ORR (43.2% vs. 5.6%), apparently superior PFS (median PFS: 17.3 vs. 9.6 months, P=0.016) and OS (median OS: not reached vs. 25.7 months, P=0.005) over TKI monotherapy. Bulk and single-cell RNA-seq data revealed an enrichment of memory and effect T cells in responders to ICI plus TKI combination therapy. Furthermore, we identified a signature of memory and effect T cells that was associated with the effectiveness of ICI plus TKI combination therapy. CONCLUSIONS: ICI plus TKI combination therapy may represent a promising treatment option for metastatic FH-deficient RCC. A memory/active T cell-derived signature is associated with the efficacy of ICI+TKI but necessitates further validation.

The clinicopathologic and molecular features, and treatment outcome of fumarate hydratase-deficient renal cell carcinoma: a retrospective comparison with type 2 papillary renal cell carcinoma.

BACKGROUND: To compare clinicopathologic, molecular features, and treatment outcome between fumarate hydratase-deficient renal cell carcinoma (FH-dRCC) and type 2 papillary renal cell carcinoma (T2 pRCC). METHODS: Data of T2 pRCC patients and FH-dRCC patients with additional next-generation sequencing information were retrospectively analyzed. The cancer-specific survival (CSS) and disease-free survival (DFS) were primary endpoint. RESULTS: A combination of FH and 2-succino-cysteine (2-SC) increased the rate of negative predictive value of FH-dRCC. Compared with T2 pRCC cases, FH-dRCC cases displayed a greater prevalence in young patients, a higher frequency of radical nephrectomy. Seven FH-dRCC and two T2 pRCC cases received systemic therapy. The VEGF treatment was prescribed most frequently, with an objective response rate (ORR) of 22.2% and a disease control rate (DCR) of 30%. A combined therapy with VEGF and checkpoint inhibitor reported an ORR of 40% and a DCR of 100%. FH-dRCC cases showed a shortened CSS (P = 0.042) and DFS (P < 0.001). The genomic sequencing revealed 9 novel mutations. CONCLUSIONS: Coupled with genetic detection, immunohistochemical biomarkers (FH and 2-SC) can distinguish the aggressive FH-dRCC from T2 pRCC. Future research is awaited to illuminate the association between the novel mutations and the clinical phenotypes of FH-dRCC in the disease progression.

Development and validation of a nomogram for predicting the impact of tumor size on cancer-specific survival of locally advanced renal cell carcinoma: a SEER-based study.

This study was aimed to integrate tumor size with other prognostic factors into a prognostic nomogram to predict cancer-specific survival (CSS) in locally advanced (≥pT3a Nany M0) renal cell carcinoma (RCC) patients. Based on the Surveillance, Epidemiology, and End Results (SEER) database, 10,800 patients diagnosed with locally advanced RCC were collected. They were randomly divided into a training cohort (n = 7,056) and a validation cohort (n = 3,024). X-tile program was used to identify the optimal cut-off value of tumor size and age. The cut-off of age at diagnosis was 65 years old and 75 years old. The cut-off of tumor size was 54 mm and 119 mm. Univariate and multivariate Cox regression analyses were performed in the training cohort to identify independent prognostic factors for construction of nomogram. Then, the nomogram was used to predict the 1-, 3- and 5-year CSS. The performance of nomogram was evaluated by using concordance index (C-index), area under the Subject operating curve (AUC) and decision curve analysis (DCA). Moreover, the nomogram and tumor node metastasis (TNM) staging system (AJCC 8th edition) were compared. 10 variables were screened to develop the nomogram. The area under the receiver operating characteristic (ROC) curve (AUC) indicated satisfactory ability of the nomogram. Compared with the AJCC 8th edition of TNM stage, DCA showed that the nomogram had improved performance. We developed and validated a nomogram for predicting the CSS of patients with locally advanced RCC, which was more precise than the AJCC 8th edition of TNM staging system.

GSDMB: A novel, independent prognostic marker and potential new therapeutic target in clear cell renal cell carcinoma.

Gasdermin (GSDM) family members are involved in numerous biological processes, including pyroptosis, as well as in the initiation and progression of various types of cancer. However, the specific role of GSDM genes in clear cell renal cell carcinoma (ccRCC) has yet to be fully clarified. The present study investigated the differential expression and genetic alterations GSDM genes, their effects on prognosis and immune modulation, and their functional enrichment in ccRCC. Several bioinformatics databases were used, including UALCAN, The Cancer Genome Atlas, Gene Expression Profiling Interactive Analysis, Metascape, Tumor Immune Estimation Resource, GSCALite and cBioPortal. The results revealed that the expression levels of GSDMA, GSDMB, GSDMC and GSDMD were significantly upregulated in cancer tissues compared with those in paracancerous tissues in patients with ccRCC, whereas the expression of DFNB59 exhibited the opposite trend. The results were experimentally validated in patients with ccRCC, and it was confirmed that the expression levels of GSDMA, GSDMB, GSDMC, GSDMD and GSDME (DFNA5) were significantly enhanced, whereas (PJVK, DFNB59) expression was reduced. In addition, elevated GSDMB, GSDMD and DFNA5 expression levels were clearly associated with worse pathological characteristics of ccRCC, including a high pathological stage and high tumor grade. Furthermore, the high expression levels of GSDMB, GSDMC, GSDMD, DFNA5 and PJVK were shown to be associated with worse overall survival (OS) and progression-free interval in patients with ccRCC. Both univariate and multivariate analyses indicated that the expression of GSDMB was independently associated with the OS of patients with ccRCC. Additionally, a high mutation rate of GSDM genes (33%) was observed in patients with ccRCC, and GSDM gene mutations were also significantly associated with a poor OS in patients with ccRCC. Significant associations between GSDM genes and ccRCC immunoprofiling and drug sensitivity were also determined. In conclusion, the findings of the present study indicated that GSDMB, GSDMD and DFNA5 may be considered promising therapeutic agents and potential biomarkers for patients with ccRCC. Furthermore, GSDMB could act as an independent predictor for the OS of patients with ccRCC.

Metformin suppresses proliferation and glycolysis of gastric cancer by modulating ADAMTS12.

BACKGROUND: Gastric cancer (GC) is a common malignancy with its morbidity increasing worldwide. Hence, it is imperative to develop effective treatments. Studies have shown that metformin has potential antitumor effects. The objective of this study was to probe the antitumor mechanism of metformin in GC. METHODS: The expression of ADAMTS12 in GC tissues and its enrichment pathways were analyzed by bioinformatics methods. ADAMTS12 expression in GC cells was assessed by qRT-PCR. Cell viability and proliferation were analyzed by CCK-8 and colony formation assays, respectively. Extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) of GC cells in different treatment groups were analyzed by Seahorse XP 96, and glycolysis metabolites were detected by corresponding kits. Western blot was employed to analyze the level of glycolysis pathway related protein HK-2, and cell functional assays were conducted to verify the functions of metformin on GC cells. A xenograft model was constructed to validate the inhibitory role of metformin in GC. RESULTS: ADAMTS12 expression was elevated in GC tissues/cells and concentrated in glycolysis pathway. Cell functional assays found that ADAMTS12 promoted the proliferation and glycolysis of GC cells. Rescue experiments showed that metformin could reduce the promoting effect of ADAMTS12 overexpression on the proliferation and glycolysis of GC cells. In vivo studies confirmed that metformin suppressed the proliferation and glycolysis process via ADAMTS12 in GC cells. CONCLUSION: Metformin can repress the proliferation and glycolysis of GC cells via ADAMTS12. The results suggest the potential of ADAMTS12 being a target for the metformin therapy of GC.

Everolimus-induced hyperpermeability of endothelial cells causes lung injury.

The mammalian target of rapamycin (mTOR) inhibitors, everolimus (but not dactolisib), is frequently associated with lung injury in clinical therapies. However, the underlying mechanisms remain unclear. Endothelial cell barrier dysfunction plays a major role in the pathogenesis of the lung injury. This study hypothesizes that everolimus increases pulmonary endothelial permeability, which leads to lung injury. We tested the effects of everolimus on human pulmonary microvascular endothelial cell (HPMEC) permeability and a mouse model of intraperitoneal injection of everolimus was established to investigate the effect of everolimus on pulmonary vascular permeability. Our data showed that everolimus increased human pulmonary microvascular endothelial cell (HPMEC) permeability which was associated with MLC phosphorylation and F-actin stress fiber formation. Furthermore, everolimus induced an increasing concentration of intracellular calcium Ca2+ leakage in HPMECs and this was normalized with ryanodine pretreatment. In addition, ryanodine decreased everolimus-induced phosphorylation of PKCα and MLC, and barrier disruption in HPMECs. Consistent with in vitro data, everolimus treatment caused a visible lung-vascular barrier dysfunction, including an increase in protein in BALF and lung capillary-endothelial permeability, which was significantly attenuated by pretreatment with an inhibitor of PKCα, MLCK, and ryanodine. This study shows that everolimus induced pulmonary endothelial hyper-permeability, at least partly, in an MLC phosphorylation-mediated EC contraction which is influenced in a Ca2+-dependent manner and can lead to lung injury through mTOR-independent mechanisms.

ALKBH5-mediated CHAC1 depletion promotes malignant progression and decreases cisplatin-induced oxidative stress in gastric cancer.

The m6a demethyltransferase ALKBH5 dynamically modulates gene expression and intracellular metabolic molecules by modifying RNA m6a in cancer cells. However, ALKBH5's function in gastric cancer (GC) has remained controversial. This study demonstrates that ALKBH5 is highly expressed in GC. Silencing ALKBH5 hampers proliferation, and metastatic potential, and induces cell death in GC cells. Through a comprehensive analysis of the transcriptome and m6A sequencing, alterations in certain ALKBH5 target genes, including CHAC1, were identified. ALKBH5's demethylation effect regulates CHAC1 RNA stability, leading to reduced CHAC1 expression. Moreover, CHAC1 modulates intracellular ROS levels, influencing the chemotherapy sensitivity of gastric cancer. In summary, our study unveils the pivotal role of the ALKBH5-CHAC1-ROS axis and highlights the significance of m6A methylation in gastric cancer.

PECAM-1 mediates temsirolimus-induced increase in neutrophil transendothelial migration that leads to lung injury.

Temsirolimus is a first-generation mTOR inhibitor commonly used in the clinical treatment of cancers that is associated with lung injury. However, the mechanism underlying this adverse effect remains elusive. Endothelial barrier dysfunction plays a pivotal role in the infiltration of neutrophils into the pulmonary alveoli, which eventually induces lung injury. The present study demonstrates that temsirolimus induces the aberrant expression of adhesion molecules in endothelial cells, leading to enhanced neutrophil infiltration and subsequent lung injury. Results of a mouse model revealed that temsirolimus disrupted capillary-alveolar barrier function and facilitated neutrophil transmigration across the endothelium within the alveolar space. Consistent with our in vivo observations, temsirolimus impaired intercellular barrier function within monolayers of human lung endothelial cells, resulting in increased neutrophil infiltration. Furthermore, we demonstrated that temsirolimus-induced neutrophil transendothelial migration was mediated by platelet endothelial cell adhesion molecule-1 (PECAM-1) in both in vitro and in vivo experiments. Collectively, these findings highlight that temsirolimus induces endothelial barrier dysfunction via PECAM-1-dependent pathway both in vitro and in vivo, ultimately leading to neutrophil infiltration and subsequent pulmonary injury.

Prognostic value of platelet combined with serum procalcitonin in patients with sepsis.

Sepsis, a common and life-threatening condition in critically ill patients, is a leading cause of death in intensive care units. Over the past few decades, there has been significant improvement in the understanding and management of sepsis. However, the mortality rate remains unacceptably high, posing a prominent challenge in modern medicine and a significant global disease burden. A total of 295 patients with sepsis admitted to the hospital from January 2021 to December 2022 were collected and divided into survival group and death group according to their 28-day survival status. The differences in general clinical data and laboratory indicators between the 2 groups were compared. Receiver operating characteristic curve analysis was used to evaluate the predictive value of platelet (PLT) and procalcitonin (PCT) for the prognosis of sepsis patients within 28 days. A total of 295 patients were diagnosed with sepsis, and 79 died, with a mortality rate of 26.78%. The PLT level in the death group was lower than that in the survival group; the PCT level in the death group was higher than that in the survival group. The receiver operating characteristic curve showed that the area under the curve of PCT and PLT for evaluating the prognosis of sepsis patients were 0.808 and 0.804, respectively. Kaplan-Meier survival analysis showed that the 28-day survival rate of the low PLT level group was 19.0% and that of the high PLT level group was 93.1% at the node of 214.97 × 109/L, and the difference between the 2 groups was statistically significant (χ2 = 216.538, P < .001). The 28-day survival rate of the low PCT level group was 93.4% and that of the high PCT level group was 51.7% at the node of 2.85 ng/mL, and the difference between the 2 groups was statistically significant (χ2 = 63.437, P < .001). There was a negative correlation between PCT level and PLT level (r = -0.412, P < .001). Platelet combined with serum procalcitonin detection has high predictive value for judging the 28-day prognosis of sepsis, and it can be used as an index for evaluating the patient's condition and prognosis, and is worthy of clinical promotion and application.

Risk factors and their interactive effects on severe acute pancreatitis complicated with acute gastrointestinal injury.

BACKGROUND: There are many risk factors for severe acute pancreatitis (SAP) complicated with acute gastrointestinal injury (AGI), but few reports on the interaction between these risk factors. AIM: To analyze the risk factors for SAP complicated with AGI and their interactive effects. METHODS: We selected 168 SAP patients admitted to our hospital between December 2019 and June 2022. They were divided into AGI group and non-AGI group according to whether AGI was present. Demographic data and laboratory test data were compared between the two groups. The risk factors for SAP with concomitant AGI were analyzed using multifactorial logistic regression, and an analysis of the interaction of the risk factors was performed. RESULTS: The percentage of patients with multiple organ dysfunction syndrome, acute physiological and chronic health scoring system II (APACHE II) score, white blood cell count and creatinine (CRE) level was higher in the AGI group than in the non-AGI group. There was a statistically significant difference between the two groups (P < 0.05). Logistic regression analysis indicated that an APACHE II score > 15 and CRE > 100 µmol/L were risk factors for SAP complicating AGI. The interaction index of APACHE II score and CRE level was 3.123. CONCLUSION: An APACHE II score > 15 and CRE level > 100 µmol/L are independent risk factors for SAP complicated with AGI, and there is a positive interaction between them.

Disitamab vedotin in combination with immune checkpoint inhibitors for locally and locally advanced bladder urothelial carcinoma: a two-center's real-world study.

Objective: Our study aims to assess the effectiveness and safety profile of Disitamab Vedotin (DV, RC48-ADC), an innovative humanized anti-HER2 antibody conjugated with tubulin-disrupting antimitotic drug monomethyl auristatin E (MMAE) via a cleavable peptide linker. This treatment combined immune checkpoint inhibitors as part of the bladder sparing approach for selected patients suffering from locally and locally advanced bladder urothelial carcinoma. Patients and methods: We conducted a two-center, real-world study involving locally advanced urothelial carcinoma (UC) patients. Patients were classified based on HER2 expression (IHC 3+/2+/1+) or lack of HER2 expression (IHC 0). The primary endpoint was the objective response rate (ORR), assessed by the investigator following the criteria of RECIST V1.1. Secondary endpoints encompassed the pathological complete response rate (pCR), pathological partial response rate (pPR), and pathological stable disease (pSD), along with recurrence-free survival (RFS), the pathological downstaging rate, and the safety profile of the treatment. Results: In this study, nine patients were enrolled, with a median follow-up duration of 12.0 months. The overall confirmed ORR was 88.9%, Five patients achieved a complete response (CR), and three patients achieved a partial response (PR). The radiological complete response (rCR) aligned perfectly with pCR. The median radiological progression-free survival (rPFS) spanned 12.0 months (range from 8.0 to 17.0 months). One patient diagnosed with disease progression (PD) underwent a radical cystectomy. The pathological stage evolved from T2N0M0 to T3aN2M0, followed by adjuvant chemotherapy with a gemcitabine-cisplatin (GC) combination radiotherapy. At the 9-month follow-up, neither recurrence nor metastasis was observed. The rate and intensity of complications were manageable among these patients, with no evidence of grade 4 and 5 adverse events. Conclusion: The combination of DV and PD-1 demonstrated considerable activity in the objective response rate (ORR) in patients with HER2 IHC 0/1+/2+/3+ muscle-invasive bladder cancer (MIBC), along with the longest reported median radiological progression-free survival (rPFS) to date. With an extended duration of treatment, the safety profile of DV plus PD-1 was also confirmed to be manageable.

Integrative analysis of circadian clock with prognostic and immunological biomarker identification in ovarian cancer.

Objective: To identify circadian clock (CC)-related key genes with clinical significance, providing potential biomarkers and novel insights into the CC of ovarian cancer (OC). Methods: Based on the RNA-seq profiles of OC patients in The Cancer Genome Atlas (TCGA), we explored the dysregulation and prognostic power of 12 reported CC-related genes (CCGs), which were used to generate a circadian clock index (CCI). Weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network were used to identify potential hub genes. Downstream analyses including differential and survival validations were comprehensively investigated. Results: Most CCGs are abnormally expressed and significantly associated with the overall survival (OS) of OC. OC patients with a high CCI had lower OS rates. While CCI was positively related to core CCGs such as ARNTL, it also showed significant associations with immune biomarkers including CD8+ T cell infiltration, the expression of PDL1 and CTLA4, and the expression of interleukins (IL-16, NLRP3, IL-1ß, and IL-33) and steroid hormones-related genes. WGCNA screened the green gene module to be mostly correlated with CCI and CCI group, which was utilized to construct a PPI network to pick out 15 hub genes (RNF169, EDC4, CHCHD1, MRPL51, UQCC2, USP34, POM121, RPL37, SNRPC, LAMTOR5, MRPL52, LAMTOR4, NDUFB1, NDUFC1, POLR3K) related to CC. Most of them can exert prognostic values for OS of OC, and all of them were significantly associated with immune cell infiltration. Additionally, upstream regulators including transcription factors and miRNAs of key genes were predicted. Conclusion: Collectively, 15 crucial CC genes showing indicative values for prognosis and immune microenvironment of OC were comprehensively identified. These findings provided insight into the further exploration of the molecular mechanisms of OC.

Intermittent fever and cough in a 56-year-old patient: Relapsing polychondritis and extranodal NK/T-cell lymphoma.

Relapsing polychondritis (RP) is a rare autoimmune disease in which recurrent and progressive chondritis occurs throughout the body. We report a case of a 56-year-old female subject presented as intermittent fever and cough, who was found obvious luminal stenosis and intense 18F-fluorodeoxyglucose (FDG) uptake in her larynx and trachea via bronchoscopy and FDG positron emission tomography/computed tomography (PET/CT). The auricular cartilage biopsy demonstrated chondritis. At first she was diagnosed as RP and treated by glucocorticoid and methotrexate, leading to completely response. Fever and cough recurred after 18 months, and FDG PET/CT were performed again and targeted a newfound nasopharyngeal lesion, where the biopsy proved to be an extranodal natural killer (NK)/T-cell lymphoma, nasal type.

Genomic and transcriptomic features between primary and paired metastatic fumarate hydratase-deficient renal cell carcinoma.

BACKGROUND: Fumarate hydratase-deficient renal cell carcinoma (FH-RCC) is a rare highly aggressive subtype of kidney cancer for which the distinct genomic, transcriptomic, and evolutionary relationships between metastatic and primary lesions are still unclear. METHODS: In this study, whole-exome, RNA-seq, and DNA methylation sequencing were performed on primary-metastatic paired specimens from 19 FH-RCC cases, including 23 primary and 35 matched metastatic lesions. Phylogenetic and clonal evolutionary analyses were used to investigate the evolutionary characteristics of FH-RCC. Transcriptomic analyses, immunohistochemistry, and multiple immunofluorescence experiments were performed to identify the tumor microenvironmental features of metastatic lesions. RESULTS: Paired primary and metastatic lesions generally showed similar characteristics of tumor mutation burden, tumor neoantigen burden, microsatellite instability score, CNV burden, and genome instability index. Notably, we identified an FH-mutated founding MRCA (the most recent common ancestor) clone that dominated the early evolutionary trajectories in FH-RCC. Although both primary and metastatic lesions manifested high immunogenicity, metastatic lesions exhibited higher enrichment of T effector cells and immune-related chemokines, together with upregulation of PD-L1, TIGIT, and BTLA. In addition, we found that concurrent NF2 mutation may be associated with bone metastasis and upregulation of cell cycle signature in metastatic lesions. Furthermore, although in FH-RCC metastatic lesions in general shared similar CpG island methylator phenotype with primary lesions, we found metastatic lesions displaying hypomethylated chemokine and immune checkpoints related genomic loci. CONCLUSIONS: Overall, our study demonstrated the genomic, epigenomic, and transcriptomic features of metastatic lesions in FH-RCC and revealed their early evolutionary trajectory. These results provided multi-omics evidence portraying the progression of FH-RCC.

dupA + H. pylori reduces diversity of gastric microbiome and increases risk of erosive gastritis.

Helicobacter pylori is believed to induce gastropathy; however, the exact pathogenic molecules involved in this process have not been elucidated. Duodenal ulcer promoting gene A (DupA) is a virulence factor with a controversial role in gastric inflammation and carcinogenesis. To explore and confirm the function of DupA in gastropathy from the perspective of the microbiome, we investigated the microbial characteristics of 48 gastritis patients through 16S rRNA amplicon sequencing. In addition, we isolated 21 H. pylori strains from these patients and confirmed the expression of dupA using PCR and qRT-PCR. Bioinformatics analysis identified diversity loss and compositional changes as the key features of precancerous lesions in the stomach, and H. pylori was a characteristic microbe present in the stomach of the gastritis patients. Co-occurrence analysis revealed that H. pylori infection inhibits growth of other gastric inhabiting microbes, which weakened the degradation of xenobiotics. Further analysis showed that dupA+ H. pylori were absent in precancerous lesions and were more likely to appear in erosive gastritis, whereas dupA- H. pylori was highly abundant in precancerous lesions. The presence of dupA in H. pylori caused less disturbance to the gastric microbiome, maintaining the relatively richness of gastric microbiome. Overall, our findings suggest that high dupA expression in H. pylori is correlated with a high risk of erosive gastritis and a lower level of disturbance to the gastric microbiome, indicating that DupA should be considered a risk factor of erosive gastritis rather than gastric cancer.

Highly Sensitive and Omnidirectionally Stretchable Bioelectrode Arrays for In Vivo Neural Interfacing.

Flexible electrode array, a new-generation neural microelectrode, is a crucial tool for information exchange between living tissues and external electronics. Till date, advances in flexible neural microelectrodes are limited because of their high impedance and poor mechanical consistency at tissue interfaces. Herein, a highly sensitive and omnidirectionally stretchable polymeric electrode array (PEA) is introduced. Micropyramid-nanowire composite structures are constructed to increase the effective surface area of PEA, achieving an exponential reduction in impedance compared with gold (Au) and flat polypyrrole electrodes. Moreover, for the first time, a suspended umbrella structure to enable PEA with omnidirectional stretchability of up to ≈20% is designed. The PEA can withstand 1000 cycles of mechanical loads without decrease in performance. As a proof of concept, PEA is conformally attached to a rat heart and tibialis anterior muscle, and electrophysiological signals (electrocardiogram and electromyogram) of the rat are successfully recorded. This strategy provides a new perspective toward highly sensitive and omnidirectionally stretchable PEA that can facilitate the practical application of neural electrodes.

A Nonswelling Hydrogel with Regenerable High Wet Tissue Adhesion for Bioelectronics.

Reducing the swelling of tissue-adhesive hydrogels is crucial for maintaining stable tissue adhesion and inhibiting tissue inflammation. However, reported strategies for reducing swelling always result in a simultaneous decrease in the tissue adhesive strength of the hydrogel. Furthermore, once the covalent bonds break in the currently reported hydrogels, they cannot be rebuilt, and the hydrogel loses its tissue adhesive ability. In this work, a nonswelling hydrogel (named as "PAACP") possessing regenerable high tissue adhesion is synthesized by copolymerizing and crosslinking poly(vinyl butyral) with acrylic acid, gelatin, and chitosan-grafted N-acetyl-l-cysteine. The tissue adhesive strength of the obtained PAACP reaches 211.4 kPa, which is approximately ten times higher than that of the reported nonswelling hydrogels, and the hydrogel can be reused for multiple cycles. The as-prepared hydrogel shows great potential in soft bioelectronics, as muscle fatigue is successfully monitored via the electrode array and strain sensor integrated on PAACP substrates. The success of these bioelectronics offers potential applicability in the long-term diagnosis of muscle-related health conditions and prosthetic manipulations.

Spindle function and Wnt pathway inhibition by PBX1 to suppress tumor progression via downregulating DCDC2 in colorectal cancer.

PBX1 is a transcription factor that regulates a variety of genes, involved in intracellular lipid metabolism, cell proliferation, and other pathways. The promoting and inhibiting function of PBX1 in various cancer types was extensively discussed, however, there have been no studies on PBX1 proteins in colorectal cancer (CRC). This study aimed to reveal the anti-tumor function of PBX1 in CRC and the underlying molecular mechanism. Bioinformatics analysis revealed that PBX1 is downregulated in CRC, indicating that is a potential antioncogene in CRC. Overexpression of PBX1 suppresses tumor growth and metastasis in vitro and in vivo. Mechanistically, we found that PBX1 acted as a transcription factor that suppressed DCDC2 expression and inhibited spindle function. Moreover, the PBX1-DCDC2 axis controlled the Wnt pathway in CRC cells. Overexpression of DCDC2 restored CRC proliferation, metastasis abilities and Wnt pathway. In conclusion, this study suggests that PBX1 acts as a transcription factor to suppress DCDC2 expression and inhibit cell proliferation and metastasis by disrupting spindle function and the Wnt pathway in CRC.