Mesenchymal condensation in tooth development and regeneration: a focus on translational aspects of organogenesis.

The teeth are vertebrate-specific, highly specialized organs performing fundamental functions of mastication and speech, the maintenance of which is crucial for orofacial homeostasis and is further linked to systemic health and human psychosocial well-being. However, with limited ability for self-repair, the teeth can often be impaired by traumatic, inflammatory, and progressive insults, leading to high prevalence of tooth loss and defects worldwide. Regenerative medicine holds the promise to achieve physiological restoration of lost or damaged organs, and in particular an evolving framework of developmental engineering has pioneered functional tooth regeneration by harnessing the odontogenic program. As a key event of tooth morphogenesis, mesenchymal condensation dictates dental tissue formation and patterning through cellular self-organization and signaling interaction with the epithelium, which provides a representative to decipher organogenetic mechanisms and can be leveraged for regenerative purposes. In this review, we summarize how mesenchymal condensation spatiotemporally assembles from dental stem cells (DSCs) and sequentially mediates tooth development. We highlight condensation-mimetic engineering efforts and mechanisms based on ex vivo aggregation of DSCs, which have achieved functionally robust and physiologically relevant tooth regeneration after implantation in animals and in humans. The discussion of this aspect will add to the knowledge of development-inspired tissue engineering strategies and will offer benefits to propel clinical organ regeneration.

Evolution of the thermostability of actin-depolymerizing factors enhances the adaptation of pollen germination to high temperature.

Double fertilization in many flowering plants (angiosperms) often occurs during the hot summer season, but the mechanisms that enable angiosperms to adapt specifically to high temperatures are largely unknown. The actin cytoskeleton is essential for pollen germination and the polarized growth of pollen tubes, yet how this process responds to high temperatures remains unclear. Here, we reveal that the high thermal stability of 11 Arabidopsis (Arabidopsis thaliana) actin-depolymerizing factors (ADFs) is significantly different: ADFs that specifically accumulate in tip-growing cells (pollen and root hairs) exhibit high thermal stability. Through ancestral protein reconstruction, we found that subclass II ADFs (expressed specifically in pollen) have undergone a dynamic wave-like evolution of the retention, loss, and regeneration of thermostable sites. Additionally, the sites of AtADF7 with high thermal stability are conserved in ADFs specific to angiosperm pollen. Moreover, the high thermal stability of ADFs is required to regulate actin dynamics and turnover at high temperatures to promote pollen germination. Collectively, these findings suggest strategies for the adaptation of sexual reproduction to high temperature in angiosperms at the cell biology level.

Dual elastography to discriminate adjacent stages of fibrosis and inflammation in chronic hepatitis B: A prospective multicenter study.

BACKGROUND AND AIMS: To evaluate the diagnostic performance of dual elastography (dual-elasto) in continuous differentiation of liver fibrosis and inflammation in a large prospective cohort of patients with chronic HBV. APPROACH AND RESULTS: Adults with positive HBsAg for at least 6 months were recruited from 12 medical centers. Participants underwent dual-elasto evaluations. Biopsy was performed 3 days after dual-elasto examination. Four logistic regression models were trained and strung together into series models. Decision trees based on the series models were performed to achieve continuous differentiation of liver fibrosis and inflammation. The influence of inflammation on the fibrosis stage was also evaluated. A total of 560 patients were included in the training set and 240 in the validation set. Areas under the receiver operating characteristic curve of the series model were 0.82, 0.86, 0.93, and 0.96 to predict ≥F1, ≥F2, ≥F3, and F4 in the validation set, which were significantly higher than those of serum markers and shear wave elastography (all p < 0.05), except for the ≥ F1 levels ( p = 0.09). The AUCs of the series model were 0.93, 0.86, 0.95, and 0.84 to predict inflammation stages ≥G1, ≥G2, ≥G3, and G4, respectively. Decision trees realized 5 continuous classifications of fibrosis and inflammation. Inflammation could enhance the mild fibrosis stage classification while showing limited influences on severe fibrosis or cirrhosis diagnosis. CONCLUSIONS: Dual-elasto demonstrated high performance in the continuous discrimination of fibrosis and inflammation in patients with HBV and could be used to diagnose mild fibrosis without the influence of inflammation.

Arrestin-3 binds parkin and enhances parkin-dependent mitophagy.

Arrestins were discovered for their role in homologous desensitization of G-protein-coupled receptors (GPCRs). Later non-visual arrestins were shown to regulate several signaling pathways. Some of these pathways require arrestin binding to GPCRs, the regulation of others is receptor independent. Here, we demonstrate that arrestin-3 binds the E3 ubiquitin ligase parkin via multiple sites, preferentially interacting with its RING0 domain. Identification of the parkin domains involved suggests that arrestin-3 likely relieves parkin autoinhibition and/or stabilizes the enzymatically active "open" conformation of parkin. Arrestin-3 binding enhances ubiquitination by parkin of the mitochondrial protein mitofusin-1 and facilitates parkin-mediated mitophagy in HeLa cells. Furthermore, arrestin-3 and its mutant with enhanced parkin binding rescue mitofusin-1 ubiquitination and mitophagy in the presence of the Parkinson's disease-associated R275W parkin mutant, which is defective in both functions. Thus, modulation of parkin activity via arrestin-3 might be a novel strategy of anti-parkinsonian therapy.

Integrating network pharmacology and experimental validation reveals therapeutic effects of D-mannose on NAFLD through mTOR suppression.

Non-alcoholic fatty liver disease (NAFLD), a chronic liver condition and metabolic disorder, has emerged as a significant health issue worldwide. D-mannose, a natural monosaccharide widely existing in plants and animals, has demonstrated metabolic regulatory properties. However, the effect and mechanism by which D-mannose may counteract NAFLD have not been studied. In this study, network pharmacology followed by molecular docking analysis was utilized to identify potential targets of mannose against NAFLD, and the leptin receptor-deficient, genetically obese db/db mice was employed as an animal model of NAFLD to validate the regulation of D-mannose on core targets. As a result, 67 targets of mannose are predicted associated with NAFLD, which are surprisingly centered on the mechanistic target of rapamycin (mTOR). Further analyses suggest that mTOR signaling is functionally enriched in potential targets of mannose treating NAFLD, and that mannose putatively binds to mTOR as a core mechanism. Expectedly, repeated oral gavage of supraphysiological D-mannose ameliorates liver steatosis of db/db mice, which is based on suppression of hepatic mTOR signaling. Moreover, daily D-mannose administration reduced hepatic expression of lipogenic regulatory genes in counteracting NAFLD. Together, these findings reveal D-mannose as an effective and potential NAFLD therapeutic through mTOR suppression, which holds translational promise.

Oxygen-Vacancy-Reinforced Vanadium Oxide/Graphene Heterojunction for Accelerated Zinc Storage with Long Life Span.

Vanadium trioxide (V6 O13 ) cathode has recently aroused intensive interest for aqueous zinc-ion batteries (AZIBs) due to their structural and electrochemical diversities. However, it undergoes sluggish reaction kinetics and significant capacity decay during prolonged cycling. Herein, an oxygen-vacancy-reinforced heterojunction in V6 O13- x /reduced graphene oxide (rGO) cathode is designed through electrostatic assembly and annealing strategy. The abundant oxygen vacancies existing in V6 O13- x weaken the electrostatic attraction with the inserted Zn2+ ; the external electric field constructed by the heterointerfaces between V6 O13- x and rGO provides additional built-in driving force for Zn2+ migration; the oxygen-vacancy-enriched V6 O13- x highly dispersed on rGO fabricates the interconnected conductive network, which achieves rapid Zn2+ migration from heterointerfaces to lattice. Consequently, the obtained 2D heterostructure exhibits a remarkable capacity of 424.5 mAh g-1 at 0.1 A g-1 , and a stable capacity retention (96% after 5800 cycles) at the fast discharge rate of 10 A g-1 . Besides, a flexible pouch-type AZIB with real-life practicability is fabricated, which can successfully power commercial products, and maintain stable zinc-ion storage performances even under bending, heavy strikes, and pressure condition. A series of quantitative investigation of pouch batteries demonstrates the possibility of pushing pouch-type AZIBs to realistic energy storage market.

Treatment-related pneumonitis after thoracic radiotherapy/chemoradiotherapy combined with anti-PD-1 monoclonal antibodies in advanced esophageal squamous cell carcinoma.

PURPOSE: This study aims to evaluate the risk factors of treatment-related pneumonitis (TRP) following thoracic radiotherapy/chemoradiotherapy combined with anti-PD­1 monoclonal antibodies (mAbs) in patients with advanced esophageal squamous cell carcinoma (ESCC). METHODS: We retrospectively reviewed 97 patients with advanced ESCC who were treated with thoracic radiotherapy/chemoradiotherapy combined with anti-PD­1 mAbs. Among them, 56 patients received concurrent radiotherapy with anti-PD­1 mAbs and 41 patients received sequential radiotherapy with anti-PD­1 mAbs. The median prescribed planning target volume (PTV) dose was 59.4 Gy (range from 50.4 to 66 Gy, 1.8-2.2 Gy/fraction). Clinical characteristics, the percentage of lung volume receiving more than 5-50 Gy in increments of 5 Gy (V5-V50, respectively) and the mean lung dose (MLD) were analyzed as potential risk factors for TRP. RESULTS: 46.4% (45/97), 20.6% (20/97), 20.6% (20/97), 4.1% (4/97), and 1.0% (1/97) of the patients developed any grade of TRP, grade 1 TRP, grade 2 TRP, grade 3 TRP, and fatal (grade 5) TRP, respectively. Anti-PD­1 mAbs administered concurrently with radiotherapy, V5, V10, V15, V25, V30, V35, V40 and MLD were associated with the occurrence of grade 2 or higher TRP. Concurrent therapy (P = 0.010, OR = 3.990) and V5 (P = 0.001, OR = 1.126) were independent risk factors for grade 2 or higher TRP. According to the receiver operating characteristic (ROC) curve analysis, the optimal V5 threshold for predicting grade 2 or higher TRP was 55.7%. CONCLUSION: The combination of thoracic radiotherapy/chemoradiotherapy with anti-PD­1 mAbs displayed a tolerable pulmonary safety profile. Although the incidence of TRP was high, grade 1-2 TRP accounted for the majority. Anti-PD­1 mAbs administered concurrently with radiotherapy and the lung V5 were significantly associated with the occurrence of grade 2 or higher TRP. Therefore, it seems safer to control V5 below 55% in clinical, especially for the high-risk populations receiving concurrent therapy.

Associations of social jetlag with physical activity and sedentary behaviour in children and adolescents: A systematic review and meta-analysis.

Sleep and daytime movement behaviours occur co-dependently with each other within a finite 24 h day. Sleep parameters other than sleep duration, such as social jetlag and chronotype, have been linked to health problems and unhealthy behaviours among children and adolescents. Given the increasing number of studies examining sleep timing/chronotype and weight-related behaviours, including physical activity and sedentary behaviour, in the past decade, this systematic review and meta-analysis collated and evaluated the evidence on the relationships of social jetlag and chronotype with physical activity and sedentary behaviour among children and adolescents aged 3-17 years. Seven databases were searched on 16 March 2022, and 52 studies were identified as eligible for inclusion, 47 of which were suitable for the meta-analysis. A positive association was found between social jetlag and screen media use (r = 0.14, 95% CI: 0.04-0.24; I2 = 96%; p = 0.008). The morning chronotype was associated with a higher level of physical activity and a lower level of sedentary behaviour than the evening chronotype. No relationship was found between social jetlag and physical activity. The magnitude of heterogeneity among the included studies was high. Further experimental studies are urgently required to understand how circadian preference or misalignment affects activity behaviours. Interventions to promote an active lifestyle in young populations should consider their circadian preference, especially among individuals with the evening chronotype.

Clinico-pathological study of esophageal mucoepidermoid carcinoma: a 10-year survival from a single center.

BACKGROUND: Mucoepidermoid Carcinoma of the Esophagus (MECE) is a relatively rare tumor type, with most of the current data derived from case reports or small sample studies. This retrospective study reports on the 10-year survival data and detailed clinicopathological characteristics of 48 patients with esophageal MEC. METHODS: Data were collected from 48 patients who underwent curative surgery for esophageal MEC at the Fourth Hospital of Hebei Medical University between January 1, 2004, and December 31, 2020. These were compared with contemporaneous cases of Esophageal Squamous Cell Carcinoma (ESCC) and Esophageal Adenocarcinoma (EAC). Using the Kaplan-Meier method and multivariate Cox regression analysis, we investigated the clinicopathological factors affecting the survival of patients with MEC. RESULTS: The incidence of MECE was predominantly higher in males, with a male-to-female ratio of approximately 7:1. The mid-thoracic segment emerged as the most common site of occurrence. A mere 6.3% of cases were correctly diagnosed preoperatively. The lymph node metastasis rate stood at 35.4%. The overall 1-year, 3-year, 5-year, and 10-year survival rates for all patients were 85.4%, 52.1%, 37.0%, and 31.0%, respectively. Post 1:1 propensity score matching, no significant statistical difference was observed in the Overall Survival (OS) between MEC patients and those with Esophageal Squamous Cell Carcinoma (ESCC) and Esophageal Adenocarcinoma (EAC) (P = 0.119, P = 0.669). Univariate analysis indicated that T staging and N staging were the primary factors influencing the prognosis of esophageal MEC. CONCLUSIONS: MECE occurs more frequently in males than females, with the mid-thoracic segment being the most common site of occurrence. The rate of accurate preoperative endoscopic diagnosis is low. The characteristic of having a short lesion length yet exhibiting significant extramural invasion may be a crucial clinicopathological feature of MECE. The OS of patients with MEC does not appear to significantly differ from those with esophageal squamous carcinoma and adenocarcinoma.

Co-Removal of Perfluorooctanoic Acid and Nitrate from Water by Coupling Pd Catalysis with Enzymatic Biotransformation.

PFAS (poly- and per-fluorinated alkyl substances) represent a large family of recalcitrant organic compounds that are widely used and pose serious threats to human and ecosystem health. Here, palladium (Pd0)-catalyzed defluorination and microbiological mineralization were combined in a denitrifying H2-based membrane biofilm reactor to remove co-occurring perfluorooctanoic acid (PFOA) and nitrate. The combined process, i.e., Pd-biofilm, enabled continuous removal of ∼4 mmol/L nitrate and ∼1 mg/L PFOA, with 81% defluorination of PFOA. Metagenome analysis identified bacteria likely responsible for biodegradation of partially defluorinated PFOA: Dechloromonas sp. CZR5, Kaistella koreensis, Ochrobacterum anthropic, and Azospira sp. I13. High-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and metagenome analyses revealed that the presence of nitrate promoted microbiological oxidation of partially defluorinated PFOA. Taken together, the results point to PFOA-oxidation pathways that began with PFOA adsorption to Pd0, which enabled catalytic generation of partially or fully defluorinated fatty acids and stepwise oxidation and defluorination by the bacteria. This study documents how combining catalysis and microbiological transformation enables the simultaneous removal of PFOA and nitrate.

Reliability and validity of the cancer-related dysfunctional beliefs and attitudes about sleep scale in cancer patients.

BACKGROUND: Insomnia is a common health problem among cancer patients, which is not only a physical problem but also a psychological problem. Sleep plays an important role in the mental and somatic rehabilitation of cancer patients, and the sleep beliefs and attitudes of cancer patients are key factors in improving their sleep situation and quality of life. The aim of this study was to translate the Cancer-Related Dysfunctional Beliefs and Attitudes about Sleep (C-DBAS-14) scale into Chinese and to validate its reliability and validity in cancer patients. METHOD: The C-DBAS-14 scale was translated into Chinese using the backward and forward translation procedure. The reliability of the scale was measured by internal consistency, split-half reliability and retest reliability. The validity of the scale was assessed through the content validity indicators, exploratory factor analysis and validation factor analysis. RESULT: The Cronbach's ɑ coefficient of the Chinese version of the C-DBAS-14 was 0.932 while the McDonald's omega coefficient (ω t) was 0.934. The split-half reliability coefficient was 0.908, and the test-retest reliability was 0.857. The four-factor model was obtained using exploratory factor analysis, explaining 72.7% of the variance, with each item loading greater than 0.4 on the common factor. The results of the confirmatory factor analysis revealed that all indicators of model fit were within an acceptable range, indicating a well-fitting model. CONCLUSION: The Chinese version of the C-DBAS-14 has good reliability and validity among cancer patients. It can be used to measure the sleep beliefs and attitudes of Chinese cancer patients.

RotatedStomataNet: a deep rotated object detection network for directional stomata phenotype analysis.

KEY MESSAGE: Innovatively, we consider stomatal detection as rotated object detection and provide an end-to-end, batch, rotated, real-time stomatal density and aperture size intelligent detection and identification system, RotatedeStomataNet. Stomata acts as a pathway for air and water vapor in the course of respiration, transpiration, and other gas metabolism, so the stomata phenotype is important for plant growth and development. Intelligent detection of high-throughput stoma is a key issue. Nevertheless, currently available methods usually suffer from detection errors or cumbersome operations when facing densely and unevenly arranged stomata. The proposed RotatedStomataNet innovatively regards stomata detection as rotated object detection, enabling an end-to-end, real-time, and intelligent phenotype analysis of stomata and apertures. The system is constructed based on the Arabidopsis and maize stomatal data sets acquired destructively, and the maize stomatal data set acquired in a non-destructive way, enabling the one-stop automatic collection of phenotypic, such as the location, density, length, and width of stomata and apertures without step-by-step operations. The accuracy of this system to acquire stomata and apertures has been well demonstrated in monocotyledon and dicotyledon, such as Arabidopsis, soybean, wheat, and maize. The experimental results that the prediction results of the method are consistent with those of manual labeling. The test sets, the system code, and their usage are also given ( https://github.com/AITAhenu/RotatedStomataNet ).

The effect of different high-intensity interval training protocols on cardiometabolic and inflammatory markers in sedentary young women: A randomized controlled trial.

Few studies have reported the cardiovascular health effects of different high-intensity interval training (HIIT) protocols among sedentary young women. We investigated the impact of a traditional HIIT programme and a high-intensity circuit training (HICT) programme on lipid profiles and inflammatory cytokine levels in sedentary young women. Forty-two women were randomly assigned to HICT (body weight-based training), HIIT (cycling-based training), or control groups (n = 14 each). HICT and HIIT participants completed an 8-week training programme of three sessions per week. Total cholesterol (TC), triglyceride, high- and low-density lipoprotein, leptin, resistin, tumour necrosis factor-alpha (TNF-α), interleukin-8, and interferon-gamma levels were measured before and after the intervention. Post-intervention, TC and leptin were decreased in the HICT group. The HICT group also demonstrated increased lean mass, upper and lower limb strength, and balance, while the HIIT group displayed improved lower limb strength. Additionally, the control group showed significant increases in triglyceride levels, weight, body mass index, and fat mass. In conclusion, although both HICT and HIIT interventions showed improvements in cardiovascular health and physical fitness, participants in the HICT group experienced more health benefits.

Application of a Novel Miniaturized Histopathologic Microscope for Ex Vivo Identifying Cerebral Glioma Margins Rapidly During Surgery: A Parallel Control Study.

PURPOSE: The purpose of our study is to assess the clinical performance of the DiveScope, a novel handheld histopathologic microscope in rapidly differentiating glioma from normal brain tissue during neurosurgery. METHODS: Thirty-two ex vivo specimens from 18 patients were included in the present study. The excised suspicious tissue was sequentially stained with sodium fluorescein and methylene blue and scanned with DiveScope during surgery. The adjacent tissue was sent to the department of pathology for frozen section examination. They would eventually be sent to the pathology department later for hematoxylin and eosin staining for final confirmation. The positive likelihood ratio, negative likelihood ratio, sensitivity, specificity, and area under the curve of the device were calculated. In addition, the difference in time usage between DiveScope and frozen sections was compared for the initial judgment. RESULTS: The sensitivity and specificity of the DiveScope after analyzing hematoxylin and eosin -staining sections, were 88.29% and 100%, respectively. In contrast, the sensitivity and specificity of the frozen sections histopathology were 100% and 75%, respectively. The area under the curve of the DiveScope and the frozen sections histopathology was not significant ( P =0.578). Concerning time usage, DiveScope is significantly much faster than the frozen sections histopathology no matter the size of tissue. CONCLUSION: Compared with traditional pathological frozen sections, DiveScope was faster and displayed an equal accuracy for judging tumor margins intraoperatively.

A novel simplified approach for endodontic retrograde surgery in short single-rooted teeth.

BACKGROUND: High technical thresholds, long operative times, and the need for expensive and specialized equipment impede the widespread adoption of endodontic microsurgery in many developing countries. This study aimed to compare the effects of a simplified, cost-effective, and time-efficient surgical approach involving orthograde obturation using biological ceramic material greater than 6 mm combined with apicoectomy for single-rooted teeth with short lengths with those of the conventional and current standard methods. MATERIALS AND METHODS: Forty-five premolars equally categorized into three groups: conventional surgery group, standard surgery group, and modified surgery group. A µCT scan was used to calculate the volume of voids. A micro-leakage test and scanning electron microscope (SEM) were performed to assess the sealing effect. Additionally, four cases of chronic periapical periodontitis in the anterior region were selected, and the patients received either the modified approach or the standard surgery for endodontic microsurgery. RESULTS: The volumes of voids in the apical 0-3 mm of the modified group and the standard group were comparable. The micro-leakage test and SEM examination demonstrated closely bonded fillings in the dentinal walls in both the modified surgery group and standard surgery group. The outcomes of the preliminary application of this modified procedure on patients were successful at the time of the follow-up cutoff. CONCLUSIONS: The modified surgery group exhibited similar root canal filling and apical sealing abilities with the standard procedure for single-rooted teeth with short lengths (< 20 mm). The preliminary application of this modified surgical procedure achieved favorable results.

Modulating Skeletons of Covalent Organic Framework for High-Efficiency Gold Recovery.

Covalent organic frameworks (COFs) have attracted considerable attention as adsorbents for capturing and separating gold from electronic wastes. To enhance the binding capture efficiency, constructing hydrogen-bond nanotraps along the pore walls was one of the most widely adopted approaches. However, the development of absorbing skeletons was ignored due to the weak binding ability of the gold salts (Au). Herein, we demonstrated skeleton engineering to construct highly efficiently absorbs for Au capture. The strong electronic donating feature of diarylamine units enhanced the electronic density of binding sites (imine-linkage) and thus resulted in high capacities over 1750 mg g-1 for all three COFs. Moreover, the absorbing performance was further improved via the ionization of diarylamine units. The ionic COF achieved 90 % of the maximal adsorption capacity, 1.63 times of that from the charge-neutral COF within ten minutes, and showed remarkable uptakes of 1834 mg g-1 , exceptional selectivity (97.45 %) and cycling stability. The theoretical calculation revealed the binding sites altering from imine bonds to ionic amine sites after ionization of the frameworks, which enabled to bind the AuCl4 - via coulomb force and contributed to enhanced absorbing kinetics. This work inspires us to design molecular/ionic capture based on COFs.

[FMECA and Failure Data Analysis of Domestic Wheeled Walking-Aid].

The gradual acceleration of the aging population in China has led to an increased demand for mobility aids, and the reliability of domestic wheeled walking-aid is one of their important attributes, but there is little research on the reliability of mobility aids. This paper conducts the failure mode, effects and criticality analysis on domestic wheeled walking-aid. By collecting, collating and analyzing the 26 failure modes, the key modules are the chassis and the lifting system. The key modules are obtained, and the failure data is analyzed to find out that the lifetime distribution model is log-normal and the 0.95 lower confidence limit for reliability life of product t 0.9 is 2489.4 hours. The study aims to provide ideas for the reliability analysis of other active medical devices and calls for the formation of a reliability study review point for the industry that meets the requirements of Chinese medical device regulations.

Distinct conformational and energetic features define the specific recognition of (di)aromatic peptide motifs by PEX14.

The cycling import receptor PEX5 and its membrane-located binding partner PEX14 are key constituents of the peroxisomal import machinery. Upon recognition of newly synthesized cargo proteins carrying a peroxisomal targeting signal type 1 (PTS1) in the cytosol, the PEX5/cargo complex docks at the peroxisomal membrane by binding to PEX14. The PEX14 N-terminal domain (NTD) recognizes (di)aromatic peptides, mostly corresponding to Wxxx(F/Y)-motifs, with nano-to micromolar affinity. Human PEX5 possesses eight of these conserved motifs distributed within its 320-residue disordered N-terminal region. Here, we combine biophysical (ITC, NMR, CD), biochemical and computational methods to characterize the recognition of these (di)aromatic peptides motifs and identify key features that are recognized by PEX14. Notably, the eight motifs present in human PEX5 exhibit distinct affinities and energetic contributions for the interaction with the PEX14 NTD. Computational docking and analysis of the interactions of the (di)aromatic motifs identify the specific amino acids features that stabilize a helical conformation of the peptide ligands and mediate interactions with PEX14 NTD. We propose a refined consensus motif ExWΦxE(F/Y)Φ for high affinity binding to the PEX14 NTD and discuss conservation of the (di)aromatic peptide recognition by PEX14 in other species.

Malnutrition and visceral obesity predicted adverse short-term and long-term outcomes in patients undergoing proctectomy for rectal cancer.

BACKGROUND: To the best of our knowledge, no previous studies have explored the relationship between visceral obesity and malnutrition. Therefore, this study has aimed to investigate the association between them in patients with rectal cancer. METHODS: Patients with rectal cancer who underwent proctectomy were included. Malnutrition was defined according to the Global Leadership Initiative on Malnutrition (GLIM). Visceral obesity was measured using computed tomography (CT). The patients were classified into four groups according to the presence of malnutrition or visceral obesity. Univariate and multivariate logistic regression analyses were performed to evaluate risk factors for postoperative complications. Univariate and multivariate cox regression analyses were performed to evaluate the risk factors for overall survival (OS) and cancer-specific survival (CSS). Kaplan-Meier survival curves and log-rank tests were performed for the four groups. RESULTS: This study enrolled 624 patients. 204 (32.7%) patients were included in the well-nourished non-visceral obesity (WN) group, 264 (42.3%) patients were included in the well-nourished visceral obesity (WO) group, 114 (18.3%) patients were included in the malnourished non-visceral obesity (MN) group, and 42 (6.7%) patients were included in the malnourished visceral obesity (MO) group. In the multivariate logistic regression analysis, the Charlson comorbidity index (CCI), MN, and MO were associated with postoperative complications. In the multivariate cox regression analysis, age, American Society of Anesthesiologists (ASA) score, tumor differentiation, tumor node metastasis (TNM), and MO were associated with worsened OS and CSS. CONCLUSIONS: This study demonstrated that the combination of visceral obesity and malnutrition resulted in higher postoperative complication and mortality rates and was a good indicator of poor prognosis in patients with rectal cancer.

Prognostic value of circulating tumor cells associated with white blood cells in solid cancer: a systematic review and meta-analysis of 1471 patients with solid tumors.

BACKGROUND: The clinical relevance of circulating tumor cell-white blood cell (CTC-WBC) clusters in cancer prognosis is a subject of ongoing debate. This study aims to unravel their contentious predictive value for patient outcomes. METHODS: We conducted a comprehensive literature search of PubMed, Embase, and Cochrane Library up to December 2022. Eligible studies that reported survival outcomes and examined the presence of CTC-WBC clusters in solid tumor patients were included. Hazard ratios (HR) were pooled to assess the association between CTC-WBC clusters and overall survival (OS), as well as progression-free survival (PFS)/disease-free survival (DFS)/metastasis-free survival (MFS)/recurrence-free survival (RFS). Subgroup analyses were performed based on sampling time, treatment method, detection method, detection system, and cancer type. RESULTS: A total of 1471 patients from 10 studies were included in this meta-analysis. The presence of CTC-WBCs was assessed as a prognostic factor for overall survival and PFS/DFS/MFS/RFS. The pooled analysis demonstrated that the presence of CTC-WBC clusters was significantly associated with worse OS (HR = 2.44, 95% CI: 1.74-3.40, P < 0.001) and PFS/DFS/MFS/RFS (HR = 1.83, 95% CI: 1.49-2.24, P < 0.001). Subgroup analyses based on sampling time, treatment method, detection method, detection system, cancer type, and study type consistently supported these findings. Further analyses indicated that CTC-WBC clusters were associated with larger tumor size (OR = 2.65, 95% CI: 1.58-4.44, P < 0.001) and higher alpha-fetoprotein levels (OR = 2.52, 95% CI: 1.50-4.22, P < 0.001) in hepatocellular carcinoma. However, no significant association was found between CTC-WBC clusters and TNM stage, depth of tumor invasion, or lymph node metastasis in the overall analysis. CONCLUSIONS: CTC-WBC clusters are negative predictors for OS and PFS/DFS/MFS/RFS in patients with solid tumors. Monitoring CTC-WBC levels may provide valuable information for predicting disease progression and guiding treatment decisions.