S100 protein family: Emerging role and mechanism in digestive tract cancer (Review).

Digestive tract cancer is one of the most common types of cancers globally, with ~4.8 million new cases and 3.4 million cancer­associated deaths in 2018, accounting for 26% of cancer incidence and 35% of cancer­related deaths worldwide. S100 protein family is involved in regulating cancer cell proliferation, angiogenesis, epithelial­mesenchymal transition (EMT), metastasis, metabolism and immune microenvironment homeostasis. The critical role of S100 protein family in digestive tract cancer involves complicated mechanisms, such as cancer stemness remodeling, anaerobic glycolysis regulation, tumor­associated macrophage differentiation and EMT. The present study systematically reviewed published studies on the compositions, function and the underlying molecular mechanisms of the S100 family, as well as guidance for diagnosis, treatment and prognosis of digestive tract cancer. Systematic review of the roles and underlying molecular mechanisms of S100 protein family may provide new insight into exploring potential cancer biomarkers and the optimized therapeutic strategies for digestive tract cancer.

A Strategy Inspired by the Cicada Shedding Its Skin for Synthesizing the Natural Material NaFe3 S5 ·2H2 O.

Sulfide minerals hold significant importance in both fundamental science and industrial advancement. However, certain natural sulfide minerals, such as NaFe3 S5 ·2H2 O (NFS), pose great challenges for exploitation and synthesis due to their high susceptibility to oxidation. To date, no successful precedent exists for synthesizing NFS. Here, a novel approach to synthesizing low-cost and pollution-free NFS with high stability using the high-pressure hydrothermal method based solely on knowledge of its chemical formula is presented. Moreover, an innovative strategy inspired by the cicada's molting process to develop unstable natural materials is proposed. The mechanical, thermal, optical, electrochemical, and magnetic properties of the NFS are thoroughly investigated. The storage of lithium, sodium, and potassium ions is primarily concentrated in the gap between (0 0 1) crystal planes. Additionally, as a catalyst for hydrogen evolution reaction (HER) at 10 mA cm-2 , micron-sized NFS exhibits an excellent overpotential of 6.5 mV at 90 °C, surpassing those of reported HER catalysts of similar size. This research bridges the gap in the sulfide mineral family, overcomes limitations of the high-pressure hydrothermal method, and paves the way for future synthesis of natural minerals, lunar minerals, and Martian minerals.

Advanced Composites Inspired by Biological Structures and Functions in Nature: Architecture Design, Strengthening Mechanisms, and Mechanical-Functional Responses.

The natural design and coupling of biological structures are the root of realizing the high strength, toughness, and unique functional properties of biomaterials. Advanced architecture design is applied to many materials, including metal materials, inorganic nonmetallic materials, polymer materials, and so on. To improve the performance of advanced materials, the designed architecture can be enhanced by bionics of biological structure, optimization of structural parameters, and coupling of multiple types of structures. Herein, the progress of structural materials is reviewed, the strengthening mechanisms of different types of structures are highlighted, and the impact of architecture design on the performance of advanced materials is discussed. Architecture design can improve the properties of materials at the micro level, such as mechanical, electrical, and thermal conductivity. The synergistic effect of structure makes traditional materials move toward advanced functional materials, thus enriching the macroproperties of materials. Finally, the challenges and opportunities of structural innovation of advanced materials in improving material properties are discussed.

RRP15 deficiency induces ribosome stress to inhibit colorectal cancer proliferation and metastasis via LZTS2-mediated ß-catenin suppression.

Ribosome biogenesis (RiBi) plays a pivotal role in carcinogenesis by regulating protein translation and stress response. Here, we find that RRP15, a nucleolar protein critical for RiBi and checkpoint control, is frequently upregulated in primary CRCs and higher RRP15 expression positively correlated with TNM stage (P < 0.0001) and poor survival of CRC patients (P = 0.0011). Functionally, silencing RRP15 induces ribosome stress, cell cycle arrest, and apoptosis, resulting in suppression of cell proliferation and metastasis. Overexpression of RRP15 promotes cell proliferation and metastasis. Mechanistically, ribosome stress induced by RRP15 deficiency facilitates translation of TOP mRNA LZTS2 (Leucine zipper tumor suppressor 2), leading to the nuclear export and degradation of ß-catenin to suppress Wnt/ß-catenin signaling in CRC. In conclusion, ribosome stress induced by RRP15 deficiency inhibits CRC cell proliferation and metastasis via suppressing the Wnt/ß-catenin pathway, suggesting a potential new target in high-RiBi CRC patients.

Transcriptome-Wide Dynamics of m7G-Related LncRNAs during the Progression from HBV Infection to Hepatocellular Carcinoma.

BACKGROUND: The functional ramifications of internal N7-methylguanosine (m7G) modification on RNAs have recently come to light, yet its regulatory influence on long noncoding RNAs (lncRNAs) during the inflammatory-carcinogenesis transformation process in hepatitis B virus (HBV)-mediated hepatocellular carcinoma (HCC) remains largely unexplored. METHODS: Clinical surgical samples encompassing HBV-related HCC, comprising both HCC tissue (tumor group, HBV+) and corresponding adjacent liver tissue (paracancerous group, HBV+), were collected for analysis. Additional adjacent normal liver tissues (normal group, HBV-) were acquired from patients with hepatic hemangioma, serving as controls. Employing MeRIP-seq, differential m7G levels of lncRNAs across these groups were compared to identify a subset of lncRNAs exhibiting continuous and dynamic changes in m7G modification. Subsequently, in vitro validation was conducted. RESULTS: A total of 856 lncRNAs exhibited alterations in m7G modification when compared to paracancerous tissue and normal tissue. Similarly, 1775 lncRNAs displayed changes in m7G modification when comparing HCC tissue to paracancerous tissue. For intergroup comparison, orthogonal analysis revealed that 6 lncRNAs consistently demonstrated hyper-m7G modification. In vitro validation confirmed that among these 6 lncRNAs, TEKT4P2 and DNM1P41 exhibited m7G modification-dependent expression. CONCLUSIONS: This study provides a comprehensive analysis of lncRNA m7G modification during the inflammatory-carcinogenesis transformation process in HBV-mediated HCC. The findings highlight the potential for multiple lncRNAs to undergo m7G modification changes, with TEKT4P2 and DNM1P41 identified as promising molecular targets within this intricate regulatory landscape.

Emerging role of non-coding RNAs in glucose metabolic reprogramming and chemoresistance in colorectal cancer.

Metabolic reprogramming plays a critical role in colorectal cancer (CRC). It contributes to CRC by shaping metabolic phenotypes and causing uncontrolled proliferation of CRC cells. Glucose metabolic reprogramming is common in carcinogenesis and cancer progression. Growing evidence has implicated the modifying effects of non-coding RNAs (ncRNAs) in glucose metabolic reprogramming and chemoresistance in CRC. In this review, we have summarized currently published studies investigating the role of ncRNAs in glucose metabolic alterations and chemoresistance in CRC. Elucidating the interplay between ncRNAs and glucose metabolic reprogramming provides insight into exploring novel biomarkers for the diagnosis and prognosis prediction of CRC.

Alterations of the Gut Microbiota in Patients with Diabetic Nephropathy.

Diabetic nephropathy (DN) is the primary cause of end-stage renal disease. Accumulating studies have implied a critical role for the gut microbiota in diabetes mellitus (DM) and DN. However, the precise roles and regulatory mechanisms of the gut microbiota in the pathogenesis of DN remain largely unclear. In this study, metagenomics sequencing was performed using fecal samples from healthy controls (CON) and type 2 diabetes mellitus (T2DM) patients with or without DN. Fresh fecal samples from 15 T2DM patients without DN, 15 DN patients, and 15 age-, gender-, and body mass index (BMI)-matched healthy controls were collected. The compositions and potential functions of the gut microbiota were estimated. Although no difference of gut microbiota α and ß diversity was observed between the CON, T2DM, and DN groups, the relative abundances of butyrate-producing bacteria (Clostridium, Eubacterium, and Roseburia intestinalis) and potential probiotics (Lachnospira and Intestinibacter) were significantly reduced in T2DM and DN patients. Besides, Bacteroides stercoris was significantly enriched in fecal samples from patients with DN. Moreover, Clostridium sp. 26_22 was negatively associated with serum creatinine (P < 0.05). DN patients could be accurately distinguished from CON by Clostridium sp. CAG_768 (area under the curve [AUC] = 0.941), Bacteroides propionicifaciens (AUC = 0.905), and Clostridium sp. CAG_715 (AUC = 0.908). DN patients could be accurately distinguished from T2DM patients by Pseudomonadales, Fusobacterium varium, and Prevotella sp. MSX73 (AUC = 0.889). Regarding the potential bacterial functions of the gut microbiota, the citrate cycle, base excision repair, histidine metabolism, lipoic acid metabolism, and bile acid biosynthesis were enriched in DN patients, while selenium metabolism and branched-chain amino acid biosynthesis were decreased in DN patients. IMPORTANCE Gut microbiota imbalance is found in fecal samples from DN patients, in which Roseburia intestinalis is significantly decreased, while Bacteroides stercoris is increased. There is a significant correlation between gut microbiota imbalance and clinical indexes related to lipid metabolism, glucose metabolism, and renal function. The gut microbiota may be predictive factors for the development and progression of DN, although further studies are warranted to illustrate their regulatory mechanisms.

Design and Mechanism of a Self-Powered and Disintegration-Reorganization-Regeneration Power Supply with Cold Resistance.

Up to now, power supplies designed based on the electrochemical reaction principle have had unavoidable defects, in that a complete redox reaction must be formed inside the power supply to operate normally, which makes it unable to be reconstructed and regenerated. Hence, the design and interpretation of this self-powered and disintegration-reorganization-regeneration power supply are generally considered to be almost insurmountable obstacles to haunt both experimenters and theorists. Herein, a self-powered and disintegration-reorganization-regeneration power supply with relatively stable discharge for 8.3 h is realized by the principle of ion-selective diffusion, which regenerates by radical polymerization. Additionally, the mechanism is investigated systematically by molecular dynamics simulation, and this power supply with a variety of self-powered and disintegration-reorganization-regeneration units can discharge continuously at freezing temperatures and variable temperature (0-25 °C). As a hypothetical model, a self-powered and deformable arch bridge with disintegration and reorganization is fabricated. In the future, this power supply is expected to be applied in prosthetic limbs, bionic skins, implantable power supplies, mobile phones, portable computers, wearable devices, etc. Moreover, with the improvement of the stability and discharge life, it could promote major revolutionary breakthroughs in the fields of intelligent industrial automation, smart buildings, intelligent transportation systems, intelligent power systems, etc.

Non-Coding RNAs Regulate the Resistance to Anti-EGFR Therapy in Colorectal Cancer.

Colorectal cancer (CRC) is the third prevalent cancer worldwide, the morbidity and mortality of which have been increasing in recent years. As molecular targeting agents, anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (McAbs) have significantly increased the progression-free survival (PFS) and overall survival (OS) of metastatic CRC (mCRC) patients. Nevertheless, most patients are eventually resistant to anti-EGFR McAbs. With the intensive study of the mechanism of anti-EGFR drug resistance, a variety of biomarkers and pathways have been found to participate in CRC resistance to anti-EGFR therapy. More and more studies have implicated non-coding RNAs (ncRNAs) primarily including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are widely involved in tumorigenesis and tumor progression. They function as essential regulators controlling the expression and function of oncogenes. Increasing data have shown ncRNAs affect the resistance of molecular targeted drugs in CRC including anti-EGFR McAbs. In this paper, we have reviewed the advance in mechanisms of ncRNAs in regulating anti-EGFR McAbs therapy resistance in CRC. It provides insight into exploring ncRNAs as new molecular targets and prognostic markers for CRC.

A systematic evaluation of stool DNA preparation protocols for colorectal cancer screening via analysis of DNA methylation biomarkers.

Objectives: Colorectal cancer (CRC) screening using stool samples is now in routine use where tumor DNA methylation analysis for leading markers such as NDRG4 and SDC2 is an integral part of the test. However, processing stool samples for reproducible and efficient extraction of human genomic DNA remains a bottleneck for further research into better biomarkers and assays. Methods: We systematically evaluated several factors involved in the processing of stool samples and extraction of DNA. These factors include: stool processing (solid and homogenized samples), preparation of DNA from supernatant and pellets, and DNA extraction with column and magnetic beads-based methods. Furthermore, SDC2 and NDRG4 methylation levels were used to evaluate the clinical performance of the optimal protocol. Results: The yield of total and human genomic DNA (hgDNA) was not reproducible when solid stool scraping is used, possibly due to sampling variations. More reproducible results were obtained from homogenized stool samples. Magnetic beads-based DNA extraction using the supernatant from the homogenized stool was chosen for further analysis due to better reproducibility, higher hgDNA yield, lower non-hgDNA background, and the potential for automation. With this protocol, a combination of SDC2 and NDRG4 methylation signals with a linear regression model achieved a sensitivity and specificity of 81.82 and 93.75%, respectively. Conclusions: Through the systematic evaluation of different stool processing and DNA extraction methods, we established a reproducible protocol for analyzing tumor DNA methylation markers in stool samples for colorectal cancer screening.

Proximity-effect-induced Superconducting Gap in Topological Surface States - A Point Contact Spectroscopy Study of NbSe2/Bi2Se3 Superconductor-Topological Insulator Heterostructures.

Proximity-effect-induced superconductivity was studied in epitaxial topological insulator Bi2Se3 thin films grown on superconducting NbSe2 single crystals. A point contact spectroscopy (PCS) method was used at low temperatures down to 40 mK. An induced superconducting gap in Bi2Se3 was observed in the spectra, which decreased with increasing Bi2Se3 layer thickness, consistent with the proximity effect in the bulk states of Bi2Se3 induced by NbSe2. At very low temperatures, an extra point contact feature which may correspond to a second energy gap appeared in the spectrum. For a 16 quintuple layer Bi2Se3 on NbSe2 sample, the bulk state gap value near the top surface is ~159 µeV, while the second gap value is ~120 µeV at 40 mK. The second gap value decreased with increasing Bi2Se3 layer thickness, but the ratio between the second gap and the bulk state gap remained about the same for different Bi2Se3 thicknesses. It is plausible that this is due to superconductivity in Bi2Se3 topological surface states induced through the bulk states. The two induced gaps in the PCS measurement are consistent with the three-dimensional bulk state and the two-dimensional surface state superconducting gaps observed in the angle-resolved photoemission spectroscopy (ARPES) measurement.

Momentum-dependent multiple gaps in magnesium diboride probed by electron tunnelling spectroscopy.

The energy gap is the most fundamental property of a superconductor. MgB(2), a superconductor discovered in 2001, exhibits two different superconducting gaps caused by the different electron-phonon interactions in two weakly interacting bands. Theoretical calculations predict that the gap values should also vary across the Fermi surface sheets of MgB(2). However, until now, no such variation has been observed. It has been suggested that two gap values were sufficient to describe real MgB(2) samples. Here we present an electron tunnelling spectroscopy study on MgB(2)/native oxide/Pb tunnel junctions that clearly shows a distribution of gap values, confirming the importance of the anisotropic electron-phonon interaction. The gap values, and their spreads found from the tunnel junction measurements, provide valuable experimental tests for various theoretical approaches to the multi-band superconductivity in MgB(2).

Testing an in-home gait assessment tool for older adults.

In this paper, we present results of an automatic vision-based gait assessment tool, using two cameras. Elderly residents from TigerPlace, a retirement community, were recruited to participate in the validation and test of the system in scripted scenarios representing everyday activities. The residents were first tested on a GAITRite mat, an electronic walkway that captures footfalls, and with inexpensive web cameras recording images. The extracted gait parameters from the camera system were compared with the GAITRite; excellent agreement was achieved. The residents then participated in the scenarios, with only the cameras recording. We found that the residents displayed different gait patterns during the realistic scenarios compared to the GAITRite runs. This finding provides support of the importance and advantage of continuous gait assessment in a daily living environment. Results on 4 elderly participants are included in the paper.

Gait analysis and validation using voxel data.

In this paper, we present a method for extracting gait parameters including walking speed, step time and step length from a three-dimensional voxel reconstruction, which is built from two calibrated camera views. These parameters are validated with a GAITRite Electronic mat and a Vicon motion capture system. Experiments were conducted in which subjects walked across the GAITRite mat at various speeds while the Vicon cameras recorded the motion of reflective markers attached to subjects' shoes, and our two calibrated cameras captured the images. Excellent agreements were found for walking speed. Step time and step length were also found to have good agreement given the limitation of frame rate and voxel resolution.

A real-time system for in-home activity monitoring of elders.

In this paper, we propose a real-time system for in-home activity monitoring and functional assessment for elder care. We describe the development of the whole system which could be used to assist the independent living of elders and improve the efficiency of eldercare practice. With this system, data is collected, silhouettes extracted, features further analyzed and visualized into graphs from which eldercare professionals are able to understand massive video monitoring data within a short period of time. Our experimental results demonstrate that the proposed system is efficient in indoor elder activities monitoring and easily utilized by eldercare professionals.

[Clinical analysis of 33 cases of primary esophageal small cell carcinoma].

BACKGROUND & OBJECTIVE: Esophagus is the most commonly involved site of extrapulmonary small cell carcinoma. However, no standard treatment has been established for primary esophageal small cell carcinoma. This study was to summarize the clinical characteristics, treatment, and prognosis of primary esophageal small cell carcinoma, and explore the impact of chemotherapy on the survival. METHODS: The records of 33 patients with primary esophageal small cell carcinoma, treated in Cancer Center of Sun Yat-sen University from Jan. 1985 to Dec. 2005, were reviewed to summarize the clinical characteristics and impact of therapy modality on the survival. Prognostic factors were analyzed by Kaplan-Meier and log-rank method. RESULTS: The median survival time of the 33 patients was 11.3 months; the 1-, 3-, and 5-year survival rates were 45.1%, 16.6%, and 3.5%, respectively. Clinical stage was the most important prognostic factor. The median survival time of the patients received local treatment (surgical operation or radiotherapy) was 6.3 months; the 1-, 2-, 3-year survival rates were 31.1%, 23.5%, and 8.2%, respectively. The median survival time of the patients received local treatment plus chemotherapy was 15.4 months; the 1-, 2-, 3-year survival rates were 69.3%, 34.6%, and 28.7%, respectively. CONCLUSION: Surgical operation plus chemotherapy can improve the survival of the patients with early stage primary esophageal small cell carcinoma.