Neoadjuvant chemotherapy is noninferior to chemoradiotherapy for early-onset locally advanced rectal cancer in the FOWARC trial.

BACKGROUND: The early-onset rectal cancer with rapidly increasing incidence is considered to have distinct clinicopathological and molecular profiles with high-risk features. This leads to challenges in developing specific treatment strategies for early-onset rectal cancer patients and questions of whether early-onset locally advanced rectal cancer (LARC) needs aggressive neoadjuvant treatment. METHODS: In this post hoc analysis of FOWARC trial, we investigated the role of preoperative radiation in early-onset LARC by comparing the clinicopathological profiles and short-term and long-term outcomes between the early-onset and late-onset LARCs. RESULTS: We revealed an inter-tumor heterogeneity of clinical profiles and treatment outcomes between the early-onset and late-onset LARCs. The high-risk features were more prevalent in early-onset LARC. The neoadjuvant radiation brought less benefits of tumor response and more risk of complications in early-onset group (pCR: OR = 3.75, 95% CI = 1.37-10.27; complications: HR = 11.35, 95% CI = 1.46-88.31) compared with late-onset group (pCR: OR = 5.33, 95% CI = 1.83-15.58; complications: HR = 5.80, 95% CI = 2.32-14.49). Furthermore, the addition of radiation to neoadjuvant chemotherapy didn't improve long-term OS (HR = 1.37, 95% CI = 0.49-3.87) and DFS (HR = 1.05, 95% CI = 0.58-1.90) for early-onset patients. CONCLUSION: Preoperative radiation plus chemotherapy may not be superior to the chemotherapy alone in the early-onset LARC. Our findings provide insight into the treatment of early-onset LARC by interrogating the aggressive treatment and alternative regimens.

Cyclic Ether Derived Stable Solid Electrolyte Interphase on Bismuth Anodes for Ultrahigh-Rate Sodium-Ion Storage.

The bismuth anode has garnered significant attention due to its high theoretical Na-storage capacity (386 mAh g-1). There have been numerous research reports on the stable solid electrolyte interphase (SEI) facilitated by electrolytes utilizing ether solvents. In this contribution, cyclic tetrahydrofuran (THF) and 2-methyltetrahydrofuran (MeTHF) ethers are employed as solvents to investigate the sodium-ion storage properties of bismuth anodes. A series of detailed characterizations are utilized to analyze the impact of electrolyte solvation structure and SEI chemical composition on the kinetics of sodium-ion storage. The findings reveal that bismuth anodes in both THF and MeTHF-based electrolytes exhibit exceptional rate performance at low current densities, but in THF-based electrolytes, the reversible capacity is higher at high current densities (316.7 mAh g-1 in THF compared to 9.7 mAh g-1 in MeTHF at 50 A g-1). This stark difference is attributed to the formation of an inorganic-rich, thin, and uniform SEI derived from THF-based electrolyte. Although the SEI derived from MeTHF-based electrolyte also consists predominantly of inorganic components, it is thicker and contains more organic species compared to the THF-derived SEI, impeding charge transfer and ion diffusion. This study offers valuable insights into the utilization of cyclic ether electrolytes for Na-ion batteries.

Development and validation of a simple and practical model for early detection of diabetic macular edema in patients with type 2 diabetes mellitus using easily accessible systemic variables.

OBJECTIVE: Diabetic macular edema (DME) is the leading cause of visual impairment in patients with diabetes mellitus (DM). The goal of early detection has not yet achieved due to a lack of fast and convenient methods. Therefore, we aim to develop and validate a prediction model to identify DME in patients with type 2 diabetes mellitus (T2DM) using easily accessible systemic variables, which can be applied to an ophthalmologist-independent scenario. METHODS: In this four-center, observational study, a total of 1994 T2DM patients who underwent routine diabetic retinopathy screening were enrolled, and their information on ophthalmic and systemic conditions was collected. Forward stepwise multivariable logistic regression was performed to identify risk factors of DME. Machine learning and MLR (multivariable logistic regression) were both used to establish prediction models. The prediction models were trained with 1300 patients and prospectively validated with 104 patients from Guangdong Provincial People's Hospital (GDPH). A total of 175 patients from Zhujiang Hospital (ZJH), 115 patients from the First Affiliated Hospital of Kunming Medical University (FAHKMU), and 100 patients from People's Hospital of JiangMen (PHJM) were used as external validation sets. Area under the receiver operating characteristic curve (AUC), accuracy (ACC), sensitivity, and specificity were used to evaluate the performance in DME prediction. RESULTS: The risk of DME was significantly associated with duration of DM, diastolic blood pressure, hematocrit, glycosylated hemoglobin, and urine albumin-to-creatinine ratio stage. The MLR model using these five risk factors was selected as the final prediction model due to its better performance than the machine learning models using all variables. The AUC, ACC, sensitivity, and specificity were 0.80, 0.69, 0.80, and 0.67 in the internal validation, and 0.82, 0.54, 1.00, and 0.48 in prospective validation, respectively. In external validation, the AUC, ACC, sensitivity and specificity were 0.84, 0.68, 0.90 and 0.60 in ZJH, 0.89, 0.77, 1.00 and 0.72 in FAHKMU, and 0.80, 0.67, 0.75, and 0.65 in PHJM, respectively. CONCLUSION: The MLR model is a simple, rapid, and reliable tool for early detection of DME in individuals with T2DM without the needs of specialized ophthalmologic examinations.

Copper-containing titanium alloys promote the coupling of osteogenesis and angiogenesis by releasing copper ions.

Previous investigations have reported on the ability of copper (Cu)-bearing biomaterials to accelerate vascular formation and bone regeneration. However, few studies have explored the effects of Cu-bearing materials on the interactions between angiogenesis and osteogenesis. Therefore, in this study, we prepared Cu-containing alloys using selective laser melting (SLM) technology and investigated the impact of preosteoblasts seeded on Ti6Al4V-4.5Cu alloy on angiogenesis. Our results indicated that Ti6Al4V-4.5Cu alloys increased the expression of proangiogenic genes and proteins in preosteoblasts, which further stimulated vascular formation in endothelial cells. Besides, we discovered that the biological effects of the Ti6Al4V-4.5Cu alloy were partly attributed to the release of Cu ions. In short, our research demonstrated the ability of Ti6Al4V-4.5Cu alloys to promote the coupling of angiogenesis and osteogenesis by releasing Cu ions.

Linc279227 contributes to mitochondrial dysfunction in high glucose-treated mouse renal tubular epithelial cells.

BACKGROUND: The aberrant expression of long noncoding RNAs (lncRNAs) has been associated with diabetic nephropathy (DN), a major complication of diabetes mellitus (DM). This study investigated the differential expression of lncRNAs in DM without renal damage and DM with renal damage, known as DN, and elucidated the functions of a pathogenic lncRNA. METHODS: High-throughput sequencing was performed on the kidneys of male db/db mice with kidney injury, db/db mice without kidney involvement and db/m control littermates. Linc279227 expression was confirmed by RT‒qPCR and fluorescence in situ hybridization. The effects of linc279227 on high glucose (HG)-treated renal tubular epithelial cells (RTECs) were evaluated by autophagy flux monitoring, Western blot determination and mitochondrial morphological detection. RESULTS: With high-throughput sequencing, we identified a 1024 nt long intergenic noncoding RNA, TCONS_00279227 (linc279227), whose expression was markedly increased in the kidneys of db/db mice with kidney injury compared to db/db mice without kidney injury and db/m control littermates. Fluorescence in situ hybridization confirmed that linc279227 was mainly located in the renal tubules of mice with DN. In vitro, linc279227 expression was found to be significantly increased in RTECs treated with high glucose (HG) for 48 h. Silencing linc279227 markedly restored the levels of autophagy-/mitophagy-associated proteins in HG-stimulated RTECs. Furthermore, silencing linc279227 reduced phosphorylated Drp1 expression and increased Mfn2 expression in RTECs exposed to HG. CONCLUSION: Our data suggest that linc279227 plays an important role in mitochondrial dysfunction in HG-treated RTECs and that silencing linc279227 rescues RTECs exposed to HG.

Structure and Interface Engineering of Ultrahigh-Rate 3D Bismuth Anodes for Sodium-Ion Batteries.

Sodium-ion batteries (SIBs) have attracted tremendous attention as promising low-cost energy storage devices in future grid-scale energy management applications. Bismuth is a promising anode for SIBs due to its high theoretical capacity (386 mAh g-1 ). Nevertheless, the huge volume variation of Bi anode during (de)sodiation processes can cause the pulverization of Bi particulates and rupture of solid electrolyte interphase (SEI), resulting in quick capacity decay. It is demonstrated that rigid carbon framework and robust SEI are two essentials for stable Bi anodes. A lignin-derived carbonlayer wrapped tightly around the bismuth nanospheres provides a stable conductive pathway, while the delicate selection of linear and cyclic ether-based electrolytes enable robust and stable SEI films. These two merits enable the long-term cycling process of the LC-Bi anode. The LC-Bi composite delivers outstanding sodium-ion storage performance with an ultra-long cycle life of 10 000 cycles at a high current density of 5 A g-1 and an excellent rate capability of 94% capacity retention at an ultrahigh current density of 100 A g-1 . Herein, the underlying origins of performance improvement of Bi anode are elucidated, which provides a rational design strategy for Bi anodes in practical SIBs.

Prevalent Pseudoprogression and Pseudoresidue in Patients With Rectal Cancer Treated With Neoadjuvant Immune Checkpoint Inhibitors.

BACKGROUND: Immune checkpoint inhibitor (ICI) treatment in patients with microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) tumors holds promise in reshaping organ preservation in rectal cancer. However, the benefits are accompanied by distinctive patterns of response, introducing a dilemma in the response evaluation for clinical decision-making. PATIENTS AND METHODS: Patients with locally advanced rectal cancer with MSI-H/dMMR tumors receiving neoadjuvant ICI (nICI) treatment (n=13) and matched patients receiving neoadjuvant chemoradiotherapy (nCRT; n=13) were included to compare clinical response and histopathologic features. RESULTS: Among the 13 patients receiving nICI treatment, in the final radiologic evaluation prior to surgery (at a median of 103 days after initiation of therapy), progressive disease (n=3), stable disease (n=1), partial response (n=7), and complete response (n=2) were observed. However, these patients were later confirmed as having pathologic complete response, resulting in pseudoprogression and pseudoresidue with incidences of 23.1% (n=3) and 76.9% (n=10), respectively, whereas no pseudoprogression was found in the 13 patients receiving nCRT. We further revealed the histopathologic basis underlying the pseudoprogression and pseudoresidue by discovering the distinctive immune-related regression features after nICI treatment, including fibrogenesis, dense lymphocytes, and plasma cell infiltration. CONCLUSIONS: Pseudoprogression and pseudoresidue were unique and prevalent response patterns in MSI-H/dMMR rectal cancer after nICI treatment. Our findings highlight the importance of developing specific strategies for response evaluation in neoadjuvant immunotherapy to identify patients with a good response in whom sphincter/organ-preserving or watch-and-wait strategies may be considered.

Current Surveillance After Treatment is Not Sufficient for Patients With Rectal Cancer With Negative Baseline CEA.

BACKGROUND: Serum CEA has been widely used to screen for potential recurrent disease after resection in rectal cancer. However, the influence of baseline CEA on the performance of CEA in recurrence surveillance needs to be investigated. PATIENTS AND METHODS: This longitudinal cohort study included 484 patients with nonmetastatic rectal cancer from 18,013 patients in a prospectively enrolled institutional database program of colorectal disease. Baseline CEA levels were determined before treatment, and CEA-based follow-up tests and examinations were applied in the surveillance after treatment. RESULTS: A total of 62.6% (62/99) overall, 53.5% (23/43) local, and 64.9% (50/77) distant recurrences were seen in patients who had similar CEA levels with their baseline statuses. The sensitivity of elevated CEA levels during surveillance for overall recurrence was significantly lower in patients with negative baseline CEA than in those with elevated baseline CEA levels (41.3% vs 69.4%; P =.007). Moreover, similar results were observed in the surveillance for local (50% vs 61.5%; P =.048) and distant (39.6% vs 72.4%; P =.005) recurrences between these 2 patient groups. However, CEA had comparable and excellent specificity during surveillance for recurrent disease in these groups. The addition of CA19-9 to the CEA assay significantly improved the sensitivity in recurrence surveillance for patients with negative baseline CEA (49.2% vs 41.3%; P =.037). Finally, we identified a subgroup of CEA-turn recurrences characterized by negative CEA at baseline, elevated CEA at recurrence, and worse survival outcomes after recurrence (hazard ratio, 1.88; 95% CI, 1.07-3.30; P =.026). CONCLUSIONS: In patients with rectal cancer with negative baseline CEA, serum CEA had insufficient sensitivity in recurrence surveillance after treatment, and additional surveillance may improve oncologic outcomes. Baseline CEA should be considered before CEA-based surveillance can be applied in the follow-up trials.

The Addition of Preoperative Radiation Is Insufficient for Lateral Pelvic Control in a Subgroup of Patients With Low Locally Advanced Rectal Cancer: A Post Hoc Study of a Randomized Controlled Trial.

BACKGROUND: The local recurrence of rectal cancer has been improved by total mesorectal excision following neoadjuvant chemoradiotherapy. However, in patients with low locally advanced rectal cancer, lateral pelvic recurrence remains to be addressed. OBJECTIVE: This study aimed to determine the efficiency of neoadjuvant radiotherapy in addressing lateral pelvic recurrence and which subgroup of patients might be optimal to receive lateral lymph node dissection. DESIGN: The MRI/CT images were reassessed for lateral lymph node status. The lateral lymph nodes with short axis ≥5 mm and ≥4 mm were considered positive in pretreatment and restaging MRI/CT. SETTING: This was a post hoc analysis of a prospective randomized controlled trial (FOWARC, NCT01211210). PATIENTS: A total of 495 patients with stage II or III rectal adenocarcinoma were included in the original trial. According to the excluding criteria, the finally included population consists of 253 patients; of these, 195 patients received neoadjuvant chemoradiotherapy and 94 received chemotherapy alone. MAIN OUTCOMES AND MEASURES: The primary outcome was the 5-year lateral pelvic recurrence rate. RESULTS: Compared with patients receiving chemotherapy alone, patients receiving additional radiotherapy had a marginal significance of lower lateral pelvic recurrence rate (6.6% vs 13.0%; p = 0.051). In the subset with pretreatment positive lateral lymph nodes, patients had a lateral pelvic recurrence rate of 22.6% and 45.1% after neoadjuvant chemoradiotherapy and chemotherapy alone. Of note, 34.9% of the pretreatment positive lateral lymph nodes were persistent after neoadjuvant chemoradiotherapy, culminating in a lateral pelvic recurrence rate of 63.3%. LIMITATIONS: This is a post hoc analysis, and only the patients from the leading center were included, which limited the sample size. In addition, the lateral lymph node dissection was not performed in this cohort. CONCLUSIONS: The addition of radiotherapy in neoadjuvant regimens could not address lateral pelvic recurrence adequately. Some subgroups of patients might need additional dissection. See Video Abstract at http://links.lww.com/DCR/B613. LA INCLUSION DE LA RADIOTERAPIA PREOPERATORIA ES INSUFICIIENTE EN EL CONTROL PLVICO LATERAL EN UN SUBGRUPO DE PACIENTES CON CNCER DE RECTO INFERIOR LOCALMENTE AVANZADO UN ESTUDIO POSTHOC CONTROLADO Y RANDOMIZADO: ANTECEDENTES:La recurrencia local del cancer de recto ha disminuido al efectuar una excision mesorrectal total seguida de quimioradioterapia neoadyuvante. No obstante, en pacientes con cancer de tercio inferior de recto avanzado localmente, aún está por controlarse la recurrencia pélvicaOBJETIVOS:Determinar la eficacia de la radioterapia neoadyuvante en el control de la recurrencia pélvica lateral y en que subgrupo de pacientes sería conveniente efecutar una excisión lateral de las cadenas ganglionares.DISEÑO:Se reevaluaron las imágenes tomográficas y de resonancia magnética del status de las cadenas ganglionares linfáticas laterales. Los ganglios linfáticos laterales con un eje-corto > 5 mm y ≥ 4 mm se consideraron como positivos previo al tratamiento y reestadificados con RM y TAC respectivamente.ESCENARIO:Es un análisis post hoc de un studio prospectivo randomizado controlado (FOWARC, NCT01211210).PACIENTESSe incluyeron un total de 495 pacientes en estdio II o III con adenomcarcinoma rectal en el estudio original. De acuerdo a los criterios de exclusión, la población final incluida consistió en 253 pacientes; de estos, 195 recibieron quimioradioterapia neoadyuvante y 94 quimioterapia sola.EVALUACION DE LOS RESULTADOS PRINCIPALES:El parámetro mas importante fue la tasa de recurrencia pélvica lateral a cinco años.RESULTADOS:En comparación con los pacientes que recibieron quimioterapia sola, aquellos que además fueron sometidos a radioterapia adicional presentaron un margen significativo de menor tasa de recurrencia pélvica lateral (6.6% vs. 13.0%; p=0.051). En el grupo de pacientes con ganglios linfáticos laterales positivos, los enfermos presentaron una tasa de recurrencia pélvica lateral de 22.6% y 45.1% después de quimioradiaterapia neoadyuvante en comparación con quimioterapia sola respectivamente. Cabe mencionar que el 34.9% de los pacientes con ganglios linfáticos laterales positivos antes del tratamiento persistieron después de la quimioradioterapia neoadyuvante, reportándose finalmente una recurrencia pélvica lateral de un 63.3%.LIMITACIONES:Se trata de un análisis posthoc y solo los pacientes del hospital fueron incluidos, lo que limita el tamaño de la muestra. Además, no se efectuó la disección de los ganglios linfáticos laterales en este grupo.CONCLUSIONES:La radioterapia en los esquemas de neoadyuvancia no logran controlar la recurrencia pélvica lateral en forma adecuada. Algunos subgrupos de pacientes podría requerir de disección adicional. Consulte Video Resumen en http://links.lww.com/DCR/B613.

Enhancement of NADPH availability for coproduction of coenzyme Q10 and farnesol from Rhodobacter sphaeroides.

Coenzyme Q10 (CoQ10)-an essential cofactor in the respiratory electron transport chain-has important pharmaceutical and healthcare applications. Farnesol (FOH)-an acyclic sesquiterpene alcohol-has garnered interest owing to its valuable clinical and medical benefits. Here, the coproduction of CoQ10 and FOH in Rhodobacter sphaeroides GY-2 was greatly improved through the enhancement of intracellular NADPH availability. Transcription of pgi, gdhA, and nuocd was, respectively, inhibited using RNA interference to reduce intracellular NAD(P)H consumption. Moreover, zwf, gnd, and zwf + gnd were overexpressed to enhance the pentose phosphate pathway, resulting in improved NADPH availability in most metabolically engineered R. sphaeroides strains. RSg-pgi with RNAi of pgi combined with overexpression of gnd produced 55.05 mg/L FOH that is twofold higher than the parental strain GY-2, and 185.5 mg/L CoQ10 can be coproduced at the same time. In conclusion, improved carbon flux can be redirected toward NADPH-dependent biosynthesis through the enhancement of NADPH availability.

Sugar-sweetened beverage intake and serum testosterone levels in adult males 20-39 years old in the United States.

BACKGROUND: This population-based study was designed to investigate whether consumption of sugar-sweetened beverages (SSB) is associated with lower serum total testosterone concentration in men 20-39 years old. METHODS: All data for this study were retrieved from the National Health and Nutrition Examination Survey (NHANES) 2011-2012. The primary outcome was serum testosterone concentration, and main independent variable was SSB intake. Other variables included age, race/ethnicity, poverty/income ratio, body mass index (BMI), serum cotinine, heavy drinking, and physical activity. RESULTS: Among all subjects (N = 545), 486 (90.4%) had normal testosterone levels (defined as ≥231 ng/dL) and 59 (9.6%) had low testosterone levels (defined as < 231 ng/dL). Multivariate logistic regression revealed the odds of low testosterone was significantly greater with increasing SSB consumption (Q4 [≥442 kcal/day] vs. Q1 [≤137 kcal/day]), adjusted odds ratio [aOR] = 2.29, p = 0.041]. After adjusting for possible confounding variables, BMI was an independent risk factor for low testosterone level; subjects with BMI ≥ 25 kg/m2 had a higher risk of having a low testosterone level than those with BMI < 25 kg/m2 (aOR = 3.68, p = 0.044). CONCLUSION: SSB consumption is significantly associated with low serum testosterone in men 20-39 years old in the United States.

The effect of 3 wt.% Cu addition on the microstructure, tribological property and corrosion resistance of CoCrW alloys fabricated by selective laser melting.

Microstructure, tribological property and corrosion resistance of orthopedic implant materials CoCrW-3 wt.% Cu fabricated by selective laser melting (SLM) process were systematically investigated with CoCrW as control. Equaxied γ-phase together with the inside {111} < 112 > type twin and platelet ε-phase was found in both the Cu-bearing and Cu-free alloys. Compared to the Cu-free alloy, the introduction of 3 wt.% Cu significantly increased the volume fraction of the ε-phase. In both alloys, the hardness of ε-phase zone was rather higher (~4 times) than that of γ-phase zone. The wear factor of 3 wt.% Cu-bearing alloy possessed smaller wear factor, although it had higher friction coefficient compared with Cu-free alloys. The ε-phase in the CoCr alloy would account for reducing both abrasive and fatigue wear. Moreover, the Cu-bearing alloy presented relatively higher corrosion potential Ecorr and lower corrosion current density Icorr compared to the Cu-free alloy. Accordingly, 3 wt.% Cu addition plays a key role in enhancing the wear resistance and corrosion resistance of CoCrW alloys, which indicates that the SLM CoCrW-3Cu alloy is a promising personalized alternative for traditional biomedical implant materials.

Erectile and urinary function in men with rectal cancer treated by neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy alone: a randomized trial report.

OBJECTIVE: The aim was to evaluate erectile and urinary function of male patients with rectal cancer treated by neoadjuvant (NA) chemoradiotherapy (CRT) or NA chemotherapy only. METHODS: In this prospective randomized trial (ClinicalTrials.gov NCT01211210; "FOWARC"), we included 102 men who received NA therapy for stage II-III rectal cancer between January 2011 and June 2013. Before surgery, patients received either NA mFOLFOX6 chemotherapy with radiation (RCS group, n = 54) or NA mFOLFOX6 chemotherapy alone (CS group, n = 48). Erectile and urinary dysfunctions were assessed with the five-item International Index of Erectile Function (IIEF-5) scale and the International Prostatic Symptom Score (IPSS), respectively. Questionnaires were completed at baseline and at 3, 6, and 12 months (t0-t3, respectively) after surgery. RESULTS: At t3, mean IIEF-5 score was significant higher in the CS group (15.3 ± 5.5) than in the RCS group (12.6 ± 5.7; P < 0.05). And score difference was statistically higher in RCS group compared with CS group at t2 and t3, especially t3 (9.3 ± 5.5 vs. 6.1 ± 5.1, P < 0.01). Univariate analysis of the RCS group's IIEF-5 scores associated age, stoma, location, and tumor size to erectile dysfunction. However, mean IPSS scores did not differ between the two groups at any point. CONCLUSIONS: Compared with the CS group, erectile and urinary functions were significantly affected by NA CRT. Age, stoma, tumor location, and tumor size were also correlated with erectile dysfunction in the RCS group.

[Impact of neoadjuvant radiochemotherapy followed by surgery for mid-low rectal cancer on patients' erectile function: a prospective randomized trial].

OBJECTIVE: To evaluate the erectile function of male patients treated by neoadjuvant radiochemotherapy and neoadjuvant chemotherapy alone for mid-low rectal cancer. METHODS: The clinical data of 66 patients with rectal cancer from March 2011 to March 2013 were prospectively analyzed. Of all the patients, 56 cases were finally included in the study and were randomly allocated to two groups. Thirty patients were treated by neoadjuvant radiochemotherapy followed by surgery (RCS group), and 26 were treated by neoadjuvant chemotherapy followed by surgery (NCS group). The five-item version of the international index of erectile function (IIEF-5) questionnaire were used to determine erectile function before therapy and at least 12 months after surgery. The impacts of age, location, size of tumor, and body mass index on erectile function were analyzed. RESULTS: Total score was decreased significantly at follow-up compared to initial assessment in both RCS and NCS groups (23.4 ± 1.30 vs. 11.7 ± 5.8, t = 10.748, P < 0.01; 23.1 ± 1.3 vs. 15.2 ± 6.7, t = 5.910, P < 0.01, respectively). Score difference was statistically higher in RCS group compared with NCS group (11.7 ± 5.6 vs. 8.0 ± 6.0, t = 2.394, P = 0.020). In terms of tumor location for RCS group, difference was statistically higher in the patients with low rectal cancer compared with those with middle rectal cancer (14.5 ± 3.5 vs. 9.5 ± 6.0, t = 2.894, P = 0.008). CONCLUSIONS: The erectile functions of patients treated by neoadjuvant radiochemotherapy followed by surgery are more affected than that of patients treated by neoadjuvant chemotherapy followed by surgery in mid-low rectal cancer. Also low rectal cancer are significantly associated with erectile dysfunction in the patients treated by neoadjuvant radiochemotherapy followed by surgery.

Understanding Lignin Dissolution with Urea and the Formation of a Lignin Nano-Aggregate: A Multiscale Approach.

This study employs a combined computational and experimental approach to elucidate the mechanisms governing the interaction between lignin and urea, impacting lignin dissolution and subsequent aggregation behavior. Molecular dynamics (MD) simulations reveal how the urea concentration and temperature influence lignin conformation and interactions. Higher urea concentrations and temperatures promote lignin dispersion by disrupting intramolecular interactions and enhancing solvation. Density functional theory (DFT) calculations quantitatively assess the interaction energy between lignin and urea, supporting the findings from MD simulations. Anti-solvent precipitation demonstrates that increasing the urea concentration hinders the self-assembly of lignin nanoclusters. The findings provide valuable insights for optimizing lignin biorefinery processes by tailoring the urea concentration and temperature for efficient extraction and dispersion. Understanding the influence of urea on lignin behavior opens up avenues for designing novel lignin-based materials with tailored properties. This study highlights the potential for the synergetic application of MD simulations and DFT calculations to unravel complex material interactions at the atomic level.

Highly Stable ZnS Anodes for Sodium-Ion Batteries Enabled by Structure and Electrolyte Engineering.

Zinc sulfide is a promising high-capacity anode for practical sodium-ion batteries, considering its high capacity and the low cost of zinc and sulfur sources. However, the pulverization of particulate zinc sulfide causes active mass collapse and penetration-induced short circuits of batteries. Herein, a zinc sulfide encapsulated in a nitrogen-doped carbon shell (ZnS@NC) was developed for high-performance anodes. The confinement effect of nitrogen-doped carbon stabilizes the active mass structure during cycling thanks to the robust chemically and electronically bonded connections between nitrogen-doped carbon and zinc sulfide nanoparticles. Furthermore, the cycling stability of the ZnS@NC anode is boosted by the robust inorganic-rich solid electrolyte interphase (SEI) formed in cyclic and linear ether-based electrolytes. The ZnS@NC anode displayed a reversible specific capacity of 584 mAh g-1, an excellent rate capability of 327 mAh g-1 at 70 A g-1, and a highly stable cycling performance over 10000 cycles. This work provides a practical and promising approach to designing stable conversion anodes for high-performance sodium-ion batteries.

Choline consumption reduces CVD risk via body composition modification.

Despite extensive research on the relationship between choline and cardiovascular disease (CVD), conflicting findings have been reported. We aim to investigate the relationship between choline and CVD. Our analysis screened a retrospective cohort study of 14,663 participants from the National Health and Nutrition Examination Survey conducted between 2013 and 2018. Propensity score matching and restricted cubic splines was used to access the association between choline intake and the risk of CVD. A two-sample Mendelian randomization (MR) analysis was conducted to examine the potential causality. Additionally, sets of single cell RNA-sequencing data were extracted and analyzed, in order to explore the role of choline metabolism pathway in the progression and severity of the CVD and the underlying potential mechanisms involved. The adjusted odds ratios and 95% confidence intervals for stroke were 0.72 (0.53-0.98; p = 0.035) for quartile 3 and 0.54 (0.39-0.75; p < 0.001) for quartile 4. A stratified analysis revealed that the relationship between choline intake and stroke varied among different body mass index and waist circumference groups. The results of MR analysis showed that choline and phosphatidylcholine had a predominantly negative causal effect on fat percentage, fat mass, and fat-free mass, while glycine had opposite effects. Results from bioinformatics analysis revealed that alterations in the choline metabolism pathway following stroke may be associated with the prognosis. Our study indicated that the consumption of an appropriate quantity of choline in the diet may help to protect against CVD and the effect may be choline-mediated, resulting in a healthier body composition. Furthermore, the regulation of the choline metabolism pathway following stroke may be a promising therapeutic target.

Carboxymethyl cellulose/quaternized chitosan hydrogel loaded with polydopamine nanoparticles promotes spinal cord injury recovery by anti-ferroptosis and M1/M2 polarization modulation.

Spinal cord injury (SCI) represents a catastrophic neurological condition resulting in long-term loss of motor, autonomic, and sensory functions. Recently, ferroptosis, an iron-regulated form of cell death distinct from apoptosis, has emerged as a potential therapeutic target for SCI. In this study, we developed an injectable hydrogel composed of carboxymethyl cellulose (CMC), and quaternized chitosan (QCS), loaded with modified polydopamine nanoparticles (PDA NPs), referred to as CQP hydrogel. This hydrogel effectively scavenged reactive oxygen species (ROS), prevented the accumulation of Fe2+ and lipid peroxidation associated with ferroptosis, and restored mitochondrial functions in primary neuronal cells. When administered to animal models (rats) with SCI, the CQP hydrogels improved motor function by regulating iron homeostasis, inhibiting ferroptosis, and mitigating oxidative stress injury. Both in vitro and in vivo studies corroborated the capacity of CQP hydrogels to promote the shift from M1 to M2 polarization of microglia/macrophages. These findings suggest that CQP hydrogels, functioning as a localized iron-chelating system, have potential as biomaterials to enhance recovery from SCI by targeting ferroptosis and modulating anti-inflammatory macrophages activity.

Glycolytic Activation of CD14+ Intestinal Macrophages Contributes to the Inflammatory Responses via Exosomal Membrane Tumor Necrosis Factor in Crohn's Disease.

BACKGROUND: Macrophage (Mφ) activation plays a critical role in the inflammatory response. Activated Mφ go through profound reprogramming of cellular metabolism. However, changes in their intracellular energy metabolism and its effect on inflammatory responses in Crohn's disease (CD) remain currently unclear. The aim of this study is to explore metabolic signatures of CD14+ Mφ and their potential role in CD pathogenesis as well as the underlying mechanisms. METHODS: CD14+ Mφ were isolated from peripheral blood or intestinal tissues of CD patients and control subjects. Real-time flux measurements and enzyme-linked immunosorbent assay were used to determine the inflammatory states of Mφ and metabolic signatures. Multiple metabolic routes were suppressed to determine their relevance to cytokine production. RESULTS: Intestinal CD14+ Mφ in CD patients exhibited activated glycolysis compared with those in control patients. Specifically, macrophagic glycolysis in CD largely induced inflammatory cytokine release. The intestinal inflammatory microenvironment in CD elicited abnormal glycolysis in Mφ. Mechanistically, CD14+ Mφ derived exosomes expressed membrane tumor necrosis factor (TNF), which engaged TNFR2 and triggered glycolytic activation via TNF/nuclear factor κB autocrine and paracrine signaling. Importantly, clinically applicable anti-TNF antibodies effectively prevented exosomal membrane TNF-induced glycolytic activation in CD14+ Mφ. CONCLUSIONS: CD14+ Mφ take part in CD pathogenesis by inducing glycolytic activation via membrane TNF-mediated exosomal autocrine and paracrine signaling. These results provide novel insights into pathogenesis of CD and enhance understanding of the mechanisms of anti-TNF agents.

Tannic acid and quaternized chitosan mediated puerarin-loaded octacalcium phosphate /sodium alginate scaffold for bone tissue engineering.

Current limitations in mechanical performance and foreign body reactions (FBR) often lead to implant failure, restricting the application of bioceramic scaffolds. This study presents a novel 3D-printed scaffold that combines the release of anti-inflammatory drugs with osteogenic stimulation. Initially, the inorganic and organic phases were integrated to ensure the scaffold's mechanical integrity through catechol chemistry and the electrostatic interactions between tannic acid and quaternary ammonium chitosan. Subsequently, layers of polydopamine-encapsulated puerarin-loaded zeolitic imidazolate framework-8 (ZIF-8) were self-assembled onto the stent's surface, creating the drug-loaded scaffold that improved drug release without altering the scaffold's structure. Compared with unloaded scaffolds, the puerarin-loaded scaffold demonstrated excellent osteogenic differentiation properties along with superior anti-inflammatory and osteogenic effects in a range of in vitro and in vivo studies. RNA sequencing clarified the role of the TNF and NF/κB signaling pathways in these effects, further supporting the scaffold's osteogenic potential. This study introduces a novel approach for creating drug-loaded scaffolds, providing a unique method for treating cancellous bone defects.