The depth of perineural invasion is an independent prognostic factor for stage II colorectal cancer.

BACKGROUND: Perineural invasion (PNI) is the invasion of nerves by cancer cells and is associated with poor survival in stage II colorectal cancer. However, PNI can be further subdivided according to the depth of invasion, and the depth of PNI has not been clearly linked to prognosis. METHOD: This study aimed to assess the prognostic value of different depths of PNI in stage II colorectal cancer. We defined PNI in the submucosal plexus and myenteric plexus as superficial perineural invasion (sup-PNI) and PNI in the subserous plexus as deep perineural invasion (deep-PNI). Patients were divided into three groups based on the depth of PNI: sup-PNI, deep-PNI and non-PNI. Then, univariate and multivariate Cox regression analyses were conducted to evaluate the role of PNI in the prognosis of stage II colorectal cancer. RESULTS: This study enrolled 3508 patients with stage II colorectal cancer who underwent resection for primary colorectal lesions between January 2013 and September 2019. Clinicopathological features, including elevated carcinoembryonic antigen (CEA) levels, T4 stage, poor differentiation, deficient DNA mismatch repair (dMMR), and vascular invasion, were correlated with deep-PNI. Multivariate analyses revealed that deep-PNI was associated with worse overall survival (OS; hazard ratio [HR], 3.546; 95% confidence interval [CI], 2.307-5.449; P < 0.001) and disease-free survival (DFS; HR, 2.921; 95% CI, 2.032-4.198; P < 0.001), compared with non-PNI. Conversely, no significant difference in OS or DFS was observed between the sup-PNI and non-PNI groups in multivariate analyses. CONCLUSIONS: The study demonstrated that the depth of PNI was an independent prognostic factor for patients with stage II colorectal cancer, and patients with deep PNI had a worse prognosis. Thus, patients with PNI require further subdivision according to the depth of invasion.

Life makes cities greener: The impact of dual-policy of China in urban transformation on residents' green lifestyles.

Promoting the formation of the green lifestyle (GL) is a crucial step in achieving comprehensive green transformation of urban economic and social development. The widespread adoption of GL is influenced by various environmental regulations. Previous research mainly focused on the impact of individual policies on GL from the single policy perspective. The mechanisms of the combined effects of policies have not been thoroughly explored, particularly the contributions of each policy during periods of overlap. This paper takes the dual-policy of the New-type Urbanization Policy (NUP) and Smart City Policy (SCP) in China as an example. It employs panel data collected from 271 cities in China during 2007-2019 and establishes a multi-period difference-in-difference model to identify the combined effects of the dual-policy on residents' GL. Additionally, the Shapley value decomposition method is utilized to identify the contribution magnitude of each policy when they act simultaneously. The following conclusions are yielded. Firstly, the combined effects of dual-policy are more effective than a single policy in influencing residents' GL. Secondly, the Shapley value decomposition method reveals that when both policies are simultaneously implemented, SCP contributes a greater weight compared to NUP. Thirdly, the dual-policy can promote residents' adoption of GL through mechanisms such as green technological innovation, public participation in environmental protection, and the agglomeration of tertiary industries. Fourthly, the impact of dual-policy on residents' GL varies across different types and sizes of cities. This study attempts to unseal the "black box" of how the dual-policy influences residents' GL during the green transformation of cities in China, providing theoretical references for relevant urban policies in other countries and contributing to Chinese solutions and experience to global urban green development.

Combining perineural invasion with staging improve the prognostic accuracy in colorectal cancer: a retrospective cohort study.

BACKGROUND: Current guidelines only propose the importance of perineural invasion(PNI) on prognosis in stage II colon cancer. However, the prognostic value of PNI in other stages of colorectal cancer (CRC) is ambiguous. METHODS: This single-center retrospective cohort study included 3485 CRC patients who underwent primary colorectal resection between January 2013 and December 2016 at the Sixth Affiliated Hospital of Sun Yat-sen University. Associations of PNI with overall survival (OS) and disease-free survival (DFS) were evaluated using multivariable Cox proportional hazards regression models. In addition, interaction analyses were performed to explore the prognostic effects of PNI in different clinical subgroups. RESULTS: After median follow-up of 61.9 months, we found PNI was associated with poorer OS (adjusted hazard ratio [aHR], 1.290; 95% CI, 1.087-1.531) and DFS (aHR, 1.397; 95% CI, 1.207-1.617), irrespective of tumor stage. Interestingly, the weight of PNI was found second only to incomplete resection in the nomogram for risk factors of OS and DFS in stage II CRC patients. Moreover, OS and DFS were insignificantly different between stage II patients with PNI and stage III patients (both P > 0.05). PNI was found to be an independent prognostic factor of DFS in stage III CRC (aHR: 1.514; 95% CI, 1.211-1.892) as well. Finally, the adverse effect of PNI on OS was more significant in female, early-onset, and diabetes-negative patients than in their counterparts (interaction P = 0.0213, 0.0280, and 0.0186, respectively). CONCLUSION: PNI was an important prognostic factor in CRC, more than in stage II. The survival of patients with stage II combined with perineural invasion is similar with those with stage III. PNI in stage III CRC also suggests a worse survival.

Endoscopic Stricturotomy for Patients With Postoperative Benign Anastomotic Stricture for Colorectal Cancer.

BACKGROUND: Postoperative benign anastomotic stricture is associated with colorectal anastomosis following surgery for colorectal cancer. Endoscopic stricturotomy is a novel technique that has been demonstrated to be safe and effective for the treatment of colorectal anastomotic stricture in several case reports and series. OBJECTIVE: We designed this study to investigate the efficacy of endoscopic stricturotomy for postoperative benign anastomotic stricture in patients for colorectal cancer. The primary outcomes were stricture-recurrence-free survival and reoperation-free survival. DESIGN: This is a retrospective study. SETTING: This study presents a single-center experience. PATIENTS: This retrospective study included patients with colorectal cancer who underwent surgical resection and developed anastomotic stricture between January 2014 and June 2019 and were treated with endoscopic stricturotomy. MAIN OUTCOME MEASURES: Immediate technical success of endoscopic stricturotomy and the factors associated with success and recurrence were investigated. RESULTS: Endoscopic stricturotomy was performed in 57 patients, and immediate technical success was achieved in 84% of the patients. The mean follow-up was 31.3 (15.8) months (range, 9-74 months). Postoperative benign anastomotic stricture recurred in 11 patients after initial successful endoscopic stricturotomy; 10 of the 11 recurrent patients accepted reoperation. Univariate and multivariate analysis indicated that length of stricture ≥1 cm was an independent risk factor for failure of the initial endoscopic stricturotomy (OR, 9.423; 95% CI, 1.729-51.350; p = 0.010) and the recurrence of postoperative benign anastomotic stricture after the initial endoscopic stricturotomy (OR, 13.521; 95% CI, 2.305-79.306; p = 0.004). LIMITATIONS: The study was limited by its small sample size and retrospective design. CONCLUSIONS: Endoscopic stricturotomy is a safe and effective technique for postoperative benign anastomotic stricture. However, if the length of the stricture is ≥1 cm, endoscopic stricturotomy may not be effective, and recurrence of postoperative benign anastomotic stricture is also likely. See Video Abstract at http://links.lww.com/DCR/B739. ESTRICTUROTOMA ENDOSCPICA PARA PACIENTES CON ESTRICCIN ANASTOMTICA BENIGNA POSTOPERATORIA PARA EL CNCER COLORRECTAL: ANTECEDENTES:La estenosis anastomótica benigna postoperatoria se asocia con anastomosis colorrectal después de la cirugía para el cáncer colorrectal. La estricturotomia endoscópica es una técnica novedosa que se ha demostrado que es segura y efectiva para el tratamiento de la estenosis anastomótica colorrectal en varios informes de casos o series.OBJETIVO:Diseñamos este estudio para investigar la eficacia de la estricturotomia endoscópica para la estenosis anastomótica benigna postoperatoria en pacientes con cáncer colorrectal. El resultado primario fue la supervivencia libre de restricción estricta y la supervivencia libre de reoperación.DISEÑO:Este es un estudio retrospectivo.CONFIGURACIÓN:Este estudio presenta una experiencia de un solo centro.PACIENTES:Este estudio retrospectivo incluyó pacientes con cáncer colorrectal que se sometieron a resección quirúrgica y desarrollaron estenosis anastomótica entre enero de 2014 y junio de 2019 y tratados con estricturotomia endoscópica.MEDIDAS PRINCIPALES DE RESULTADO:Éxito técnico inmediato y estenosurotomía endoscópica, los factores asociados con el éxito y la recurrencia.RESULTADOS:Se realizó estricturotomia endoscópica en 57 pacientes, y se logró un éxito técnico inmediato en el 84% de los pacientes. El seguimiento medio fue de 31,3 (15,8) meses (rango, 9 a 74 meses), el POBAS se repitió en 11 pacientes después del éxito inicial de ESt. 10 de los 11 pacientes recurrentes aceptaron la reoperación. El análisis univariado y multivariado indicó que la longitud de la estenosis ≥1 cm era un factor de riesgo independiente para el fracaso de la estricturotomia endoscópica inicial (odds ratio = 9,423; IC del 95% = 1.729-51.350; p = 0.010) y la recurrencia de estenosis anastomótica benigna postoperatoria después de la estricturotomia endoscópica inicial (odds ratio = 13,521; IC del 95% = 2,305-79,306; p = 0.004).LIMITACIONES:El estudio estuvo limitado por su pequeño tamaño de muestra y diseño retrospectivo.CONCLUSIONES:La estricturotomia endoscópica es una técnica segura y efectiva para la estructura anastomótica benigna postoperatoria. Sin embargo, si la longitud de la estenosis es ≥1 cm, la estricturotomia endoscópica puede no ser efectiva y también es probable que se repita la estenosis anastomótica benigna postoperatoria. Consulte Video Resumen en http://links.lww.com/DCR/B739.

Clinicopathological and molecular characteristics of early-onset vs late-onset colorectal cancer according to tumor location.

BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC) is rapidly increasing worldwide in decade when screening of colorectal cancer (CRC) is more prevalent. The clinicopathological and molecular characteristics of EOCRC have not yet been clarified. This study aims to evaluate clinicopathological and molecular features among EOCRC and late-onset colorectal cancer (LOCRC) patients according to different tumor locations. METHODS: We identified CRC patients from a prospectively maintained CRC database between January 2015 and December 2018. The clinicopathological and molecular characteristics including dMMR, mutation of PIK3CA, BRAF and KRAS were compared between EOCRC and LOCRC. The relationships according to different tumor locations were assessed. RESULTS: Totally 4468 patients were analyzed in this study. Compared to LOCRC patients, EOCRC patients were more likely to have status of dMMR (OR, 2.52; P < 0.001), regardless of tumor location. EOCRC patients were more likely to be detected with mutation of PIK3CA (OR, 1.24; P = 0.041), which only tended to exist in the left-side colon (OR, 1.51; P = 0.06), but not in the right-side colon or rectum. No significant difference was found for BRAF or KRAS mutation, but mutation of KRAS was more frequently found in left-side colon (OR, 1.34; P = 0.04) among EOCRC patients. CONCLUSION: Status of dMMR, mutation of PIK3CA, BRAF and KRAS was different between EOCRC and LOCRC patients according to different tumor locations, which implied that EOCRC might be a unique subgroup of CRC patients. Further investigations of molecular and genetic differences should be performed to help define new diagnosing and therapeutical strategies for EOCRC patients.

Simultaneous measurement of liquid-level and density by detecting buoyancy and hydraulic pressure: publisher's note.

This publisher's note contains corrections to Opt. Lett.45, 6843 (2020)OPLEDP0146-959210.1364/OL.412738.

Simultaneous measurement of liquid-level and density by detecting buoyancy and hydraulic pressure.

In this Letter, we propose and experimentally demonstrate a method for simultaneous and complete discriminative measurement of liquid-level and density for the first time, to the best of our knowledge. The principle is to measure the responses of optical fiber sensing units caused by buoyancy and hydraulic pressure. By utilizing a designed steel diamond structure, the sensor sensitivity is significantly improved. The theoretical models and experimental methods are analyzed in detail. For large-range liquid-level measurement, a high sensitivity of 77.3 pm/cm with resolution of 0.129 mm (accuracy of 0.149‰) is achieved. As a trade-off between density measurement and sensor capability, a dual-parameter sensing is demonstrated experimentally, which features liquid-level sensitivity of 34.7 pm/cm and density sensitivity varying from 1 to 3.44nm/g/cm3. Taking advantage of the compact size, easy fabrication, and low cost, this method has great potential in real-time intelligent monitoring of reserves and quality for industrial storage of fuels and chemicals.

Risk factor analysis for inaccurate pre-operative MRI staging in rectal cancer.

BACKGROUND: Various tumor characteristics might lead to inaccurate local MRI-defined stage of rectal cancer and the purpose of this study was to explore the clinicopathological factors that impact on the precision pre-treatment MRI-defined stage of rectal cancer. METHODS: A retrospectively analysis was conducted in non-metastatic rectal cancer patients who received radical tumor resection without neoadjuvant treatment during 2007-2015 in the Sixth Affiliated Hospital of Sun Yat-sen University. Clinical T stage and N stage defined by pelvic enhanced MRI and pathological stage were compared and patients were subdivided into accurate-staging, over-staging and under-staging subgroups. Logistic regressions were used to explore risk factors for over-staging or under-staging. RESULTS: Five hundred fifty-one cases of patients were collected. Among them, 109 cases (19.4%) of patients were over-T-staged and 50 cases (8.9%) were under-T-staged, while 78 cases (13.9%) were over-N-staged and 75 cases (13.3%) were under-N-staged. Logistic regression suggested that pre-operative bowel obstruction was risk factor for over-T-staging (OR = 3.120, 95%CI: 1.662-5.857, P < 0.001) as well as over-N-staging (OR = 3.494, 95%CI: 1.797-6.794, P < 0.001), while mucinous adenocarcinoma was a risk factor for under-N-staging (OR = 4.049, 95%CI: 1.876-8.772, P < 0.001). Patients with larger tumor size were at lower risk for over-T-staging (OR = 0.837, 95%CI: 0.717-0.976, P = 0.024) and higher risk for over-N-staging (OR = 1.434, 95%CI: 1.223-1.680, P < 0.001). CONCLUSION: Bowel obstruction, mucinous adenocarcinoma and tumor size might have impact on the pre-operative MRI T staging or N staging of rectal cancer. Our results reminded clinicians to assess clinical stage individually in such rectal cancer patients.

Location of colorectal adenomas and serrated polyps in patients under age 50.

BACKGROUND: The incidence of colorectal cancer, especially located in distal colorectum, is rising markedly in young patients. Conventional adenomas and serrated polyps have been widely recognized as precursors of colorectal cancer. AIM: To investigate the correlation of polyp feature with polyp location in patients under age 50. METHOD: Patients under age 50 who had received colonoscopy were included from 2010 to 2018. Clinical data including number, location, size, and histopathology of polyps were collected. Odd ratios and 95% confidence interval of adenomas with their location were calculated. RESULT: In total, 25,636 patients aged 18-49 were enrolled, among which 4485 patients had polyps, with polyp detection rate of 17.5%. A total of 2484 and 2387 patients had conventional adenomas and serrated polyps, respectively. 76.0% advanced adenomas and 69.5% ≥ 10-mm serrated polyps were located in the distal colorectum. The detection rate of advanced adenomas was higher in patients aged 45-49. Patients with adenomas especially advanced adenomas in the distal colorectum were more likely to have advanced adenoma in the proximal colon. CONCLUSION: Among patients under age 50, advanced adenomas and ≥ 10-mm serrated polyps were predominantly in the distal colorectum. Advanced adenomas tended to be found in patients aged 45-49. Our results might explain the rising trend of distal colorectal cancer and emphasize the necessity for colonoscopy screening among these populations.

Preoperative Percutaneous Drainage of Spontaneous Intra-Abdominal Abscess in Patients With Crohn's Disease: A Meta-Analysis.

GOALS: We aimed to compare clinical outcomes between percutaneous drainage (PD) with or without further elective surgery and initial surgery for patients with Crohn's disease (CD)-related spontaneous intra-abdominal abscess. BACKGROUND: Intra-abdominal abscess is common in patients with CD leading to significant morbidity. The role of PD before abdominal surgery in patients with CD remains controversial. STUDY: We performed a meta-analysis comparing PD and surgery as the initial approach to CD-related spontaneous intra-abdominal abscess. Overall complication and recurrent abscess were assessed. Subgroup analyses on initial PD were performed including preoperative PD and PD alone. RESULTS: A total of 9 studies including 513 patients with CD-related spontaneous intra-abdominal abscesses were included. The overall complication rate was significantly higher in patients undergoing initial surgery compared with those undergoing initial PD [odds ratio (OR)=0.58; 95% confidence interval (CI), 0.35-0.96; P=0.03]. In a subgroup analysis, preoperative PD was associated with a significant reduction in overall complication (OR=0.44; 95% CI, 0.23-0.83; P=0.01) as compared with initial surgery. The risk for recurrent abscess was higher in patients who underwent PD alone than those who underwent initial surgery (OR=2.16; 95% CI, 1.03-4.54; P=0.04). No significance difference in postoperative recurrent abscess was found between preoperative PD group and initial surgery group. CONCLUSION: Although abdominal surgery appeared to be inevitable in the majority of the patients with CD who develop intra-abdominal abscess, preoperative PD may decrease overall complication after surgery.

Routine histopathologic examination of "benign" anal lesions: is it necessary?

PURPOSE: To establish the necessity of routine histopathologic examination of specimens from hemorrhoids and anal fistula that are diagnosed preoperatively. METHODS: We reviewed histopathologic reports from hemorrhoidectomy and anal fistula excision operations performed between 2007 and 2011 in the sixth affiliated hospital of Sun Yat-sen University and Guangdong Province Traditional Chinese Medical Hospital. We evaluated the incidence of unexpected pathologic malignancy and its impact on postoperative management. RESULTS: Among the 10532 patients recruited, 8308 had undergone hemorrhoidectomy and 2224 had undergone excision of an anal fistula. Unexpected pathologic malignancy was discovered in 17 specimens (0.16 %). Overall and subgroup analysis for risk factors of malignant detection revealed unexpected pathologic malignancy was more likely to be found in people over the age of 60 years (OR = 5.516, P = 0.002 overall and OR = 5.442, P = 0.007 for hemorrhoids). CONCLUSION: Routine histopathologic examination of specimens from patients undergoing hemorrhoid or anal fistula surgery is of value for identifying unexpected pathologic malignancy. An age older than 60 years may be a remarkable risk factor.

Bone marrow mesenchymal stem cells ameliorate colitis-associated tumorigenesis in mice.

BACKGROUND AND AIMS: Bone marrow-derived mesenchymal stem cell (MSC) is widely studied in inflammatory bowel disease (IBD) in basic and clinical research. However, patients with IBD have higher risk of developing colorectal cancer and MSC has dual effect on tumorigenesis. This study aims to evaluate the role of MSC on tumorigenesis of IBD. METHODS: MSCs were isolated from the bone marrow of allogenic mice and identified by flow cytometry. Mice in the model of colitis-associated tumorigenesis induced by azoxymethane and dextran sulfate sodium were injected with MSCs. Colon length, spleen size and tumors formation were assessed macroscopically. Pro-inflammatory cytokines and STAT3 phosphorylation in colon tissues were analyzed. RESULTS: MSCs ameliorated the severity of colitis associated tumorigenesis compared with PBS control, with attenuated weight loss, longer colons and smaller spleens. Tumor number and tumor load were significantly less in the MSC group while tumor size remained comparable. Histological assessment indicated MSCs could reduce histological damage of the colon tissue. Decreased expression of pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6), and down-regulation of STAT3 phosphorylation in colon tissue were found after MSC treatment. CONCLUSION: MSCs might ameliorate the tumorigenesis of inflammatory bowel disease by suppression of expression of pro-inflammatory cytokines and STAT3 activation.

Stapled side-to-side anastomosis might be better than handsewn end-to-end anastomosis in ileocolic resection for Crohn's disease: a meta-analysis.

BACKGROUND: Ileocolic anastomosis is an essential step in the treatment to restore continuity of the gastrointestinal tract following ileocolic resection in patients with Crohn's disease (CD). However, the association between anastomotic type and surgical outcome is controversial. AIMS: The aim of this meta-analysis is to compare surgical outcomes between stapled side-to-side anastomosis (SSSA) and handsewn end-to-end anastomosis (HEEA) after ileocolic resection in patients with CD. METHODS: Studies comparing SSSA with HEEA after ileocolic resection in patients with CD were identified in PubMed and EMBASE. Outcomes such as complication, recurrence, and re-operation were evaluated. Eight studies (three randomized controlled trials, one prospective non-randomized trial, and four non-randomized retrospective trials) comparing SSSA (396 cases) and HEEA (425 cases) were included. RESULTS: As compared with HEEA, SSSA was superior in terms of overall postoperative complications [odds ratio (OR), 0.54; 95 % confidence interval (CI) 0.32-0.93], anastomotic leak (OR 0.45; 95 % CI 0.20-1.00), recurrence (OR 0.20; 95 % CI 0.07-0.55), and re-operation for recurrence (OR 0.18; 95 % CI 0.07-0.45). Postoperative hospital stay, mortality, and complications other than anastomotic leak were comparable. CONCLUSION: Based on the results of our meta-analysis, SSSA would appear to be the preferred procedure after ileocolic resection for CD, with reduced overall postoperative complications, especially anastomotic leak, and a decreased recurrence and re-operation rate.

Risk factors for synchronous high-risk polyps in patients with colorectal cancer.

Purpose: Colorectal cancer (CRC) patients may experience inadequate preoperative colonoscopy due to bowel obstruction or inadequate bowel preparation, leading to potential oversight of other polyps. We aimed to identify risk factors for CRC complicated with synchronous high-risk polyps. Methods: A retrospective analysis of 6,674 CRC patients from December 2014 to September 2018 was conducted. High-risk polyps were defined as adenomas or serrated polyps that were ≥10 mm, or with tubulovillous/villous components or high-grade dysplasia. All other polyps were defined as low-risk polyps. Patients with complete pathological and clinical information were categorized into three groups: the no polyp group, the low-risk polyp group, and the high-risk polyp group. Univariate and multivariate logistic regression analyses were performed to calculate the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for all potential risk factors. Results: Among the 4,659 eligible patients, 848 (18.2%) were found to have low-risk polyps, while 675 (14.5%) were diagnosed with high-risk polyps. In a multivariate logistic regression model, compared to patients without polyps, those with synchronous high-risk polyps were more likely to be male (OR = 2.07), aged 50 or older (OR = 2.77), have early-stage tumors (OR = 1.46), colon tumors (OR = 1.53), NRAS mutant tumors (OR = 1.66), and BRAF wild-type tumors (OR = 2.43). Conclusion: Our study has identified several risk factors associated with the presence of synchronous high-risk polyps in CRC patients. Based on these findings, we recommend that patients who exhibit these high-risk factors undergo early follow-up of colonoscopy to detect synchronous polyps early.

The Clinical Association Between the Inflammation-Nutritional Condition and Prognosis of Locally Advanced Intrahepatic Cholangiocarcinoma After R0 Resection: Evidence from Competing Risk and Propensity Matching Analysis.

Background: Intrahepatic cholangiocarcinoma (ICC) correlates with poor outcomes, necessitating the identification of prognostic factors from an inflammation-nutritional perspective in locally advanced ICC patients after R0 resection. Methods: We retrospectively reviewed the medical records of 159 locally advanced ICC patients from Sun Yat-sen University Cancer Center. Univariate and multivariate Cox regression analysis, as well as competing risk analysis, were conducted to explore prognostic variables for locally advanced ICC following surgery. To validate the robustness of our findings, we performed propensity score matching (PSM) analyses to evaluate survival differences based on inflammation-nutritional indexes. Results: Considering non-cancer-specific death as competing risk factors, both systemic immune-inflammation index (SII, HR: 1.934) and prognostic nutrition index (PNI, HR: 0.604) emerged as significant prognostic variables for locally advanced ICC after R0 resection (P < 0.05). After PSM, the survival benefit between the low and high PNI sets remained clear (median survival time: 15.7 months vs 35.1 months, P = 0.002). Although the 5-year overall survival (OS) rate of the low SII group was higher than that of the high SII group, the difference was not statistically significant (17.5% VS 27.4%, P = 0.112). Other influencing factors included tumor number, tumor diameter, preoperative carcinoembryonic antigen (CEA)and carbohydrate antigen 19-9 (CA19-9) levels, and postoperative adjuvant therapy. Conclusion: Individual inflammatory and nutritional status significantly impact the prognosis of locally advanced ICC undergoing R0 hapectomy. Oncologists should consider incorporating inflammation-nutritional conditions into the decision-making process for this subset of advanced ICC.

Thermal-Assisted Multiscale Patterning of Nonplanar Colloidal Nanostructures for Multi-Modal Anti-Counterfeiting.

Nanotransfer printing of colloidal nanoparticles is a promising technique for the fabrication of functional materials and devices. However, patterning nonplanar nanostructures pose a challenge due to weak adhesion from the extremely small nanostructure-substrate contact area. Here, the study proposes a thermal-assisted nonplanar nanostructure transfer printing (NP-NTP) strategy for multiscale patterning of polystyrene (PS) nanospheres. The printing efficiency is significantly improved from ≈3.1% at low temperatures to ≈97.2% under the glass transition temperature of PS. Additionally, the arrangement of PS nanospheres transitioned from disorder to long-range order. The mechanism of printing efficiency enhancement is the drastic drop of Young's modulus of nanospheres, giving rise to an increased contact area, self-adhesive effect, and inter-particle necking. To demonstrate the versatility of the NP-NTP strategy, it is combined with the intaglio transfer printing technique, and multiple patterns are created at both micro and macro scales at a 4-inch scale with a resolution of ≈2757 pixels per inch (PPI). Furthermore, a multi-modal anti-counterfeiting concept based on structural patterns at hierarchical length scales is proposed, providing a new paradigm of imparting multiscale nanostructure patterning into macroscale functional devices.

ELMO1 ameliorates intestinal epithelial cellular senescence via SIRT1/p65 signaling in inflammatory bowel disease-related fibrosis.

Background: Intestinal fibrosis is a common complication in inflammatory bowel disease (IBD), which still lacks of reliable markers and therapeutic options. Cellular senescence has been considered an important mechanism of intestinal fibrosis, but the underlying molecular link remains elusive. Methods: Tissues were stained using α-smooth muscle actin (α-SMA), fibronectin, and collagen I as markers of myofibroblastic differentiation. Cellular senescence was confirmed through Lamin B1 staining, senescence-associated ß-galactosidase staining, and the expression of senescence-associated secretory phenotype (SASP) factors. We explored the relationship between senescence of intestinal epithelial cells (IECs) and intestinal fibrosis, as well as the molecular mechanism underlying this interaction. The effects of irisin on cellular senescence and fibrosis were determined. Results: Here, we identify engulfment and cell motility protein 1 (ELMO1) as a novel biomarker for intestinal cellular senescence and fibrosis. In fibrostrictured tissues from patients and murine models with IBD, significantly high levels of cellular senescence score and factors were noted, which positively correlated with the fibrotic regulator fibronectin. Senescent IECs, not fibroblast itself, released SASP factors to regulate fibroblast activation. Prolonging exposure to severe and persistent injurious stimuli decreased ELMO1 expression, which dampened SIRT1 deacetylase activity, enhanced NF-κB (p65) acetylation, and thereby accelerated cellular senescence. Deletion of ELMO1 led to senescent IECs accumulation and triggered premature fibrosis in murine colitis. Furthermore, irisin, inhibiting the degradation of ELMO1, could downregulate p65 acetylation, reduce IECs senescence, and prevent incipient intestinal fibrosis in murine colitis models. Conclusions: This study reveals ELMO1 downregulation is an early symbol of intestinal senescence and fibrosis, and the altered ELMO1-SIRT1-p65 pathway plays an important role in intestinal cellular senescence and IBD-related fibrosis.

Differential Water Conservation Capacity in Broadleaved and Mixed Forest Restoration in Latosol Soil-Eroded Region, Hainan Province, China.

The water conservation capacity of the litter and soil layers of forest ecosystems improves the function of forest ecosystems in conserving soil and water. Plantation restoration plays a key role in preventing soil erosion. In order to evaluate the water conservation capacity of plantation restoration in Latosol soil-eroded region, we analyzed the litter thickness and mass, water absorption process, water holding recovery process, and soil water holding capacity of five restoration types (Hevea brasiliensis, Acacia mangium, Eucalyptus robusta, Acacia-Eucalyptus, and Acacia-Hevea) in the Mahuangling Watershed, Hainan province. The results showed that the thickness of the litter ranged from approximately 3.42 ± 0.24 to 4.73 ± 0.81 cm, and the litter mass ranged from 5.04 ± 1.52 t·ha-1 to 13.16 ± 1.76 t·ha-1, with higher litter mass in the SL layer than in the UL layer. The litter mass of A. mangium was higher than that of H. brasiliensis, E. robusta, Acacia-Eucalyptus, and Acacia-Hevea, which was 3.16 ± 1.76 t·ha-1. A. mangium forest was significantly higher than other plantation restoration types in terms of the maximum water retention capacity (Qmax) and the effective water retention capacity (Qeff). The soil bulk weight ranged from approximately 1.52 ± 0.09 to 1.59 ± 0.08 g·cm-3, and porosity ranged from 31.77 ± 4.72 to 35.62 ± 3.02%, both of which increased with the depth of the soil layer. The water holding capacity of 0-60 cm soil varied from approximately 12.94 ± 7.91 to 45.02 ± 31.79 t·ha-1, with A. mangium having the best soil permeability and the strongest soil water holding capacity. The entropy weight method was used to conduct a comprehensive evaluation, and the results showed that the water conservation capacity of the soil layer was 1.26 times higher than that of the litter layer, in which the water conservation capacity of A. mangium was the strongest, with a comprehensive evaluation value of 0.2854, which effectively intercepted rainfall and reduced surface runoff. Hence, we suggest that the planting of A. mangium should be considered in future ecological restoration projects of the erosion area of Mahuangling in order to improve the function of conserving soil and water in a restoration forest ecosystem.

Fatty Acid Oxidation Promotes Apoptotic Resistance and Proinflammatory Phenotype of CD4+ Tissue-resident Memory T cells in Crohn's Disease.

BACKGROUND & AIMS: As the most abundant memory T cells and major source of tumor necrosis factor α in the intestinal mucosa of Crohn's disease (CD) patients, CD4+ tissue-resident memory T (TRM) cells play a critical role in CD pathogenesis. We investigated the role of metabolic reprogramming in the regulation of proinflammatory and apoptosis-resistant phenotype for CD4+ TRM cells. METHODS: CD4+ TRM cells were collected from intestinal resection tissues from control and CD patients. Transcriptomic and metabolomic analysis were performed to identify metabolic characteristics of CD4+ TRM cells. Enzyme-linked immunosorbent assay and quantitative polymerase chain reaction experiments were used to assess cytokines level in CD4+ TRM cells; activation-induced cell apoptosis rate was evaluated by flow cytometry. Transwell assay and wound healing assay were performed to detect the effect of CD4+ TRM cells on the migration of normal intestinal epithelial cells. RESULTS: Transcriptomic data combined with unbiased metabolomic analysis revealed an increased fatty acid oxidation (FAO) phenotype existed in CD4+ TRM cells from CD patients. The lipidomic data and stable isotope tracer experiments demonstrated that CD4+ TRM cells up-regulated their lipid lipolysis and fatty acid uptake to fuel FAO in CD patients. Mechanistically, the activated nuclear factor kappa B signaling increased transcription of genes involved in lipid lipolysis, fatty acid uptake, and oxidation in CD4+ TRM cells from CD patients. Targeting FAO of CD4+ TRM cells reversed their apoptosis-resistant and proinflammatory phenotype in CD patients. CONCLUSIONS: CD4+ TRM cells process an accelerated FAO mediated by activated nuclear factor kappa B signaling in CD patients; targeting FAO could reverse their apoptosis-resistant and proinflammatory phenotype. These findings shed a new light on the pathogenic mechanism investigation and novel therapy development in CD patients.

Market integration and economic growth.

This study empirically examines the interplay between market integration and economic growth across nine cities within the Pearl River Delta urban agglomeration. The findings indicate that the city cluster's market integration negatively impacts regional economic development and has a negligible effect on the surrounding areas. In response, the research recommends the elimination of market trade barriers and a reduction in local protectionism within the city cluster. Additionally, infrastructure enhancement is essential to leverage the distinct comparative advantages of each city within the Pearl River Delta urban agglomeration. An efficient collaboration mechanism is crucial to amplify the collective economic potency of the region.