Mechanisms and clinical landscape of N6-methyladenosine (m6A) RNA modification in gastrointestinal tract cancers.

Epigenetics encompasses reversible and heritable chemical modifications of non-nuclear DNA sequences, including DNA and RNA methylation, histone modifications, non-coding RNA modifications, and chromatin rearrangements. In addition to well-studied DNA and histone methylation, RNA methylation has emerged as a hot topic in biological sciences over the past decade. N6-methyladenosine (m6A) is the most common and abundant modification in eukaryotic mRNA, affecting all RNA stages, including transcription, translation, and degradation. Advances in high-throughput sequencing technologies made it feasible to identify the chemical basis and biological functions of m6A RNA. Dysregulation of m6A levels and associated modifying proteins can both inhibit and promote cancer, highlighting the importance of the tumor microenvironment in diverse biological processes. Gastrointestinal tract cancers, including gastric, colorectal, and pancreatic cancers, are among the most common and deadly malignancies in humans. Growing evidence suggests a close association between m6A levels and the progression of gastrointestinal tumors. Global m6A modification levels are substantially modified in gastrointestinal tumor tissues and cell lines compared to healthy tissues and cells, possibly influencing various biological behaviors such as tumor cell proliferation, invasion, metastasis, and drug resistance. Exploring the diagnostic and therapeutic potential of m6A-related proteins is critical from a clinical standpoint. Developing more specific and effective m6A modulators offers new options for treating these tumors and deeper insights into gastrointestinal tract cancers.

Comparison of blood loss between tranexamic acid-soaked absorbable Gelfoam and topical retrograde injection via drainage catheter plus clamping in cervical laminoplasty surgery.

BACKGROUND: To compare the safety and efficacy of tranexamic acid (TXA)-soaked absorbable Gelfoam and the retrograde injection of TXA through a drain with drain-clamping in degenerative cervical laminoplasty patients. METHODS: Patients were assigned into either TXA retrograde injection (TXA-RI), TXA-soaked absorbable Gelfoam (TXA-Gel), or control groups. The demographics, operative measurements, volume and length of drainage, length of hospital stay, complete blood cell count, coagulopathy, postoperative complications, and blood transfusion were recorded. RESULTS: We enrolled 133 patients, with 44, 44, and 45 in the TXA-RI, TXA-Gel, and control groups, respectively. The baseline characteristics did not differ significantly among the three groups. The TXA-RI group exhibited a lower volume and length of postoperative drainage compared to the TXA-Gel and control groups (126.60 ± 31.27 vs. 156.60 ± 38.63 and 275.45 ± 75.27 mL; 49.45 ± 9.70 vs 58.70 ± 10.46 and 89.31 ± 8.50 hours, all P < 0.01). The TXA-RI group also had significantly shorter hospital stays compared to the control group (5.31 ± 1.18 vs 7.50 ± 1.25 days, P < 0.05) and higher hemoglobin and hematocrit levels (12.58 ± 1.67 vs 11.28 ± 1.76 g/dL; 36.62 ± 3.66% vs 33.82 ± 3.57%, both P < 0.05) at hospital discharge. In the TXA-RI and TXA-Gel groups, the D-dimmer (DD) and fibrinogen (FIB) were significantly lower than those in the control group after surgery (P < 0.05). None of the patients required blood transfusion. No complications, including thromboembolic events, were reported. CONCLUSION: Topical retrograde injection of TXA through a drain with drain-clamping at the conclusion of unilateral posterior cervical expansive open-door laminoplasty may effectively reduce postoperative blood loss and the length of hospital stays without increasing postoperative complications.

Expression, Prognostic Value, and Functional Mechanism of Polarity-Related Genes in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a common malignant tumor with high mortality and poor prognoses around the world. Within-cell polarity is crucial to cell development and function maintenance, and some studies have found that it is closely related to cancer initiation, metastasis, and prognosis. The aim of our research was to find polarity-related biomarkers which improve the treatment and prognosis of HCC. For the knowledge-driven analysis, 189 polarity-related genes (PRGs) were retrieved and curated manually from the molecular signatures database and reviews. Meanwhile, in the data-driven part, genomic datasets and clinical records of HCC was obtained from the cancer genome atlas database. The potential candidates were considered in the respect to differential expression, mutation rate, and prognostic value. Sixty-one PRGs that passed the knowledge and data-driven screening were applied for function analysis and mechanism deduction. Elastic net model combing least absolute shrinkage and selection operator and ridge regression analysis refined the input into a 12-PRG risk model, and its pharmaceutical potency was evaluated. These findings demonstrated that the integration of multi-omics of PRGs can help us in untangling the liver cancer pathogenesis as well as illustrate the underlying mechanisms and therapeutic targets.

"Click" on Alkynylated Carbon Quantum Dots: An Efficient Surface Functionalization for Specific Biosensing and Bioimaging.

Surface functionalization is an essential pre requisite for wide and specific applications of nanoparticles such as photoluminescent (PL) carbon quantum dots (CQDs), but it remains a major challenge. In this report, alkynylated CQDs, prepared from carboxyl-rich CQDs through amidation with propargylamine in the presence of 1,1'-carbonyldiimidazole, were modified efficiently with azido molecular beacon DNA through a copper(I)-catalyzed alkyne-azide cycloaddition reaction (CuAAC). As a proof-of-concept, the DNA-modified CQDs are then bonded with gold nanoparticles (AuNPs, 5 nm) through a gold-sulfur bond. Owing to the emission enhancement, this complex can then be applied to the recognition of a single-base- mismatched target. The same functionalizing strategy applied to click the alkynylated CQDs with a nuclear localization sequence (NLS) peptide showed that the NLS-modified CQDs could target the nuclei specifically. These results indicate that surface functionalization of CQDs through a nonstoichiometric copper chalcogenide nanocrystal- (nsCuCNC-) catalyzed click reaction is efficient, and has significant potential in the fields of biosensing and bioimaging.

Nonstoichiometric copper chalcogenides for photo-activated alkyne/azide cycloaddition.

Nonstoichiometric copper chalcogenides with heavy copper vacancies can be used as an effective photo-activated catalyst for the Huisgen [3+2] cycloaddition reaction as Cu(i) can be released corresponding to holes (Cu-defects) under light irradiation. These strategies expand new possibilities for carrying out prototypical click chemistry in the presence of functional groups.

One-step prepared fluorescent copper nanoclusters for reversible pH-sensing.

A one-step synthesis of water soluble and pH-responsive trypsin-stabilized fluorescent copper nanoclusters (CuNCs) was reported without using additional protective or reducing agents, and the as-prepared CuNCs exhibited highly stable properties including oxidation resistance, thermal stability and photostability.

Poly[(µ3-3,5-diisopropyl-4H-1,2,4-triazolato-κ(3) N:N':N'')silver(I)].

In the polymeric title compound, [Ag(C8H14N3)] n , the Ag(I) cation is coordinated by three N atoms from three 3,5-diisopropyl-1,2,4-triazolate anions in a T-shaped geometry. The Ag(I) cation deviates from the coordination plane by 0.014 (1) Šand the N-Ag-N bond angles are 96.85 (11), 97.72 (10) and 165.39 (12)°. The triazolate anion bridges three Ag(I) cations, forming a three-dimensional polymeric network.

A nanosized metal-organic framework of Fe-MIL-88NH2 as a novel peroxidase mimic used for colorimetric detection of glucose.

In this paper, a nanosized porous metal-organic framework, Fe-MIL-88NH2, was facilely prepared with a uniform octahedral shape by the addition of acetic acid, and for the first time was demonstrated to possess intrinsic peroxidase-like activity. Kinetic analysis and electron spin resonance measurements indicated that the catalytic behavior was consistent with typical Michaelis-Menten kinetics and follows a ping-pong mechanism. As a novel peroxidase mimic material, Fe-MIL-88NH2 shows the advantages of high catalytic efficiency, ultrahigh stability and high biocompatibility in aqueous medium compared with natural enzymes and other peroxidase nanomimetics. Here, Fe-MIL-88NH2 was used to quickly catalyze oxidation of the peroxidase substrate 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2 to produce a colored product, which provided a simple, sensitive and selective method for the colorimetric detection of glucose. Glucose could be linearly detected in the range from 2.0 × 10⁻6 to 3.0 × 10⁻4 M with a detection limit of 4.8 × 10⁻7 M, and the color variation for glucose response was also obvious by visual observation at concentrations as low as 2.0 × 10⁻6 M. More importantly, the colorimetric method could be successfully applied to the determination of glucose in diluted serum samples.

A simple green route to prepare stable silver nanoparticles with pear juice and a new selective colorimetric method for detection of cysteine.

In this work, a new cost-effective, rapid and simple method for the preparation of stable silver nanoparticles (AgNPs) was developed, which can be completed within 15 minutes at room temperature by oxidizing the reductants in pear juice with AgNO3. Compared with the most used citrate-capped AgNPs, the as-prepared AgNPs showed high stability, good biocompatibility and enhanced antibacterial activity. Based on the formation of Ag-S covalent bonds between cysteine and AgNPs as well as the electrostatic interaction of COO(-) and NH4(+) between cysteine molecules, which selectively lead to the aggregation of the as-prepared AgNPs and give a specific yellow-to-red colour change, a new selective colorimetric method for detection of cysteine was proposed with the as-prepared AgNPs by coupling the decrease of the characteristic localized surface plasmon resonance (LSPR) absorption at 406 nm of the as-prepared AgNPs and the increase of the new aggregation-induced band at 530 nm. The ratio of the absorbance at 530 nm to 406 nm (A530/A406) was found to be linearly dependent on the cysteine concentrations in the range of 5.0 × 10(-7) to 1.0 × 10(-5) M with a limit of detection of 6.8 × 10(-8) M.

Development of polymorphic microsatellite markers for Fagus pashanica (Fagaceae) using next-generation sequencing.

Fagus pashanica is an endangered and endemic tree species in China. To understand its genetic diversity and structure for effective conservation, we used next-generation sequencing data to develop a set of microsatellite markers. Twenty-three of the 68 designed loci were successfully amplified. Fifteen polymorphic loci with clear peaks were selected for further analyses in three F. pashanica populations sampled from Nanjiang, Wangcang and Pingwu counties in Sichuan Province, China. The number of alleles per locus ranged from two to 11. The levels of observed and expected heterozygosity ranged from 0.033-0.852 and 0.033-0.787, respectively. All 23 loci were also successfully amplified in F. longipetiolata and F. lucida, and 19 were successfully amplified in F. engleriana. These microsatellite markers will be useful for population genetic studies of F. pashanica and other Fagus species.

Corrigendum: Prevalence and outcomes of pancreatic enzymes elevation in patients with COVID-19: a meta-analysis and systematic review.

[This corrects the article DOI: 10.3389/fpubh.2022.865855.].

Blocking TNF-α with infliximab alleviates ovariectomy induced mechanical and thermal hyperalgesia in rats.

Studies have proved an increased expression of tumor necrosis factor alpha (TNF-α) in estrogen deficiency animals, and TNF-α also plays a role in inflammation and neuropathic pain. This study aimed to explore the relationship between TNF-α and ovariectomy induced hyperalgesia. 36 female Sparague-Dawley were included, estrogen depletion models were established by ovariectomy. Then infliximab (a TNF-α blocker) was administrated to the ovariectomized rats for 8 weeks. Pain behavioral tests were performed once a week. The bone mineral density (BMD), serum estradiol and TNF-α level were determined at the 8th week after ovariectomy. The expression of TNF-α in lumbar 5 dorsal root ganglions (L5 DRGs) was examined by immunofluorescence method. Significant hyperalgesia to mechanical and thermal stimuli in groups Ovx-1 and Ovx-2 was observed 1 week after the operation. After treated with infliximab, the pain threshold of Ovx-2 was partially restored, although still lower than the Sham group. The serum TNF-α level of Ovx-1 was significantly higher than Sham and Ovx-2. TNF-α immunofluorescence indicated a significant increase in the expression of TNF-α at L5 DRGs in group Ovx-1 when compared with groups Sham and Ovx-2. The BMD of group Ovx-2 was significantly higher than group Ovx-1 and lower than group Sham. In conclusion, TNF-α plays an important role in estrogen deficiency induced mechanical and thermal hyperalgesia, and DRG may be one site on which TNF-α acts to cause hyperalgesia. Blocking the effect of TNF-α could partially alleviate the estrogen deficiency induced hyperalgesia in rats. Thus, TNF-α may contribute to chronic pain in postmenopausal women.

Systematic back muscle exercise after percutaneous vertebroplasty for spinal osteoporotic compression fracture patients: a randomized controlled trial.

OBJECTIVE: To analyze the clinical significance of postoperative back muscle exercises after percutaneous vertebroplasty for spinal osteoporotic compression fracture patients. DESIGN: Clinical randomized controlled trials of parallel group nonpharmacologic study. SETTING: Patients practised back muscle exercises in the spinal surgery department, rehabilitation department and at their residences. SUBJECTS: Osteoporotic compression fracture patients who had undergone percutaneous vertebroplasty and processed sufficient muscle strength to participate in the training were studied. INTERVENTIONS: Patients were randomized into two groups, which were titled A and B. General postoperation therapy, including antiosteoporotic medications and education, was offered to all patients. Group B patients received additional systematic back muscle exercise. MAIN MEASURES: Both Oswestry Disability Index (ODI) and visual analogue scale (VAS) were recorded preoperatively and postoperatively at three-day, one-month, six-month, one-year and two-year follow-up. RESULTS: From January 2006 to January 2009, a total of 82 patients were assessed for eligibility, 60 patients were enrolled and randomized into two groups. Forty-two (70%) patients (20 of 30 in Group A and 22 of 30 in Group B) were successfully followed-up for two years. Systematic back muscle exercises resulted in a significant advantage in both measurements. The ODI of Group B was significantly better than Group A at the six-month, one-year and two-year follow-ups (P < 0.05). The pain level of Group B was significantly lower than in Group A at the one- and two-year follow-ups (P < 0.05). At the end of our study, the mean (SD) of the ODI in Groups A and B were 39.1 (9.14) and 23.4 (5.62); the mean (SD) of the VAS in Groups A and B were 3.4 (1.15) and 2.1 (0.84), respectively. CONCLUSIONS: Our findings suggest that the benefit of the exercises required at least six months to be observed; however, the favourable effects could last for two years. Therefore, systematic back muscle exercise should be recommended as one of the treatment guidelines for postpercutaneous vertebroplasty patients.

[Value of coronary CT angiography in assessment of bifurcation lesions].

OBJECTIVE: To evaluate the value of coronary CT angiography in assessment of bifurcation lesions. METHODS: The original image of 79 established and suspected coronary artery disease patients who underwent both coronary CT angiography and conventional artery angiography (CAG) sequentially were included in this analysis. Bifurcation lesions were assessed on primary and secondary vessels with diameter ≥ 2.0 mm, bifurcation lesions were graded according to Chen's classification. CAG was used as golden standard. The sensitivity, specificity, positive predictive value and negative predictive value were calculated. Spearman's test and Kappa test were used to evaluate the correlation and classification identity of the two methods. RESULTS: CAG evidenced 177 bifurcation lesions out of 445 bifurcation vessels and coronary CT detected 168 bifurcation lesions out of 404 bifurcation vessels with satisfactory imaging quality and 390 bifurcation vessels could be analyzed by both CAG and coronary CT. Sensitivity, specificity, positive predictive value and negative predictive value of coronary CT angiography were 94.2%, 94.6%, 90.7%, 96.1%, respectively. The results for the lesions at LM-LAD/LCX + LAD/Mid, LAD/Diag, RCA/PDA were more satisfactory and the sensitivity and specificity were as high as: 97.1% and 94.2%, 95.7% and 89.5%, 92.3% and 98.7%, respectively. There were significant correlations for evaluating the narrow degree of the opening of the bifurcation branch with these two methods (r = 0.799 58, P < 0.01) and for identifying I, II, III type bifurcation lesions (Kappa coefficient = 0.7959, P < 0.01) as well as for identifying the subtype bifurcation lesions (Kappa coefficient = 0.6328, P < 0.01) using the two methods. CONCLUSION: Coronary CT angiography is efficient in identifying the bifurcation lesions and offers a reasonable indication for bifurcation lesion classification.

Prevalence and Outcomes of Pancreatic Enzymes Elevation in Patients With COVID-19: A Meta-Analysis and Systematic Review.

Background: Although coronavirus disease 2019 (COVID-19) is considered to be a disease that mainly involves the respiratory system, an increasing number of studies have reported that COVID-19 patients had pancreatic enzymes (PE) elevation and even pancreatic injury. The study aims to determine the prevalence of PE elevation, and the relationship between elevated PE and prognosis in COVID-19 patients. Methods: A comprehensive literature search was conducted according to the PRISMA guideline in PubMed, Embase, Scopus, Web of Science, and Google Scholar for studies reporting PE elevation in patients with COVID-19 from 1st January 2020 to 24th November 2021. Results: A total of 13 studies (24,353 participants) were included in our review. The pooled prevalence of PE elevation in COVID-19 patients was 24% (18%-31%), the pooled odds ratio (OR) of mortality was 2.5 (1.7-3.6), the pooled OR of ICU admission was 4.4 (2.8-6.8), and the pooled OR of kidney injury, respiratory failure and liver injury were 3.5 (1.6-7.4), 2.0 (0.5-8.7), and 2.3 (1.4-3.9) respectively. In addition, the subgroup analysis revealed that although PE elevated to > 3 × upper normal limit (ULN) was significantly related to the mortality (OR = 4.4, 2.1-9.4), it seemed that mild elevation of PE to 1-3 ULN also had a considerable risk of mortality (OR = 2.3, 1.5-3.5). Conclusions: PE elevation was a common phenomenon in patients with COVID-19, and was associated with poor clinical outcomes. However, due to the limited numbers of included studies, the result of our study still needed to be validated. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=295630, identifier: CRD42021295630.

Self-assembly-induced luminescence of Eu3+-complexes and application in bioimaging.

Design and engineering of highly efficient emitting materials with assembly-induced luminescence, such as room-temperature phosphorescence (RTP) and aggregation-induced emission (AIE), have stimulated extensive efforts. Here, we propose a new strategy to obtain size-controlled Eu3+-complex nanoparticles (Eu-NPs) with self-assembly-induced luminescence (SAIL) characteristics without encapsulation or hybridization. Compared with previous RTP or AIE materials, the SAIL phenomena of increased luminescence intensity and lifetime in aqueous solution for the proposed Eu-NPs are due to the combined effect of self-assembly in confining the molecular motion and shielding the water quenching. As proof of concept, we also show that this system can be further applied in bioimaging, temperature measurement and HClO sensing. The SAIL activity of the rare-earth (RE) system proposed here offers a further step forward on the roadmap for the development of RE light conversion systems and their integration in bioimaging and therapy applications.

Composition-Engineered Metal-Organic Framework-Based Microneedles for Glucose-Mediated Transdermal Insulin Delivery.

Elaborately designed glucose-responsive insulin-delivery systems are highly desirable for the treatment of diabetes because it can secrete insulin depending on blood glucose levels. Herein, mimic multi-enzyme metal-organic framework (MOF)-based (insulin and glucose oxidase-loaded cobalt-doped ZIF-8, abbreviated as Ins/GOx@Co-ZIF-8) stimuli-responsive microneedles (MNs) were designed for painless glucose-mediated transdermal administration. In this work, GOx and Co2+ ions were engineered into MOFs to construct a mimic multi-enzyme vehicle. GOx in the MOF, as the glucose-responsive factor, could catalyze glucose into gluconic acid with the formation of H2O2 as the byproduct. The gluconic acid formed decreases the local pH in MOFs, resulting in the degradation of MOFs and thus preloaded insulin would be released. Meanwhile, catalyzed by Co2+ ions in the MOF, the byproduct H2O2 was decomposed. Possible free Co2+ ions would be chelated by EDTA-SiO2 nanoparticles in MNs and removed by peeling MNs off. The as-obtained mimic multi-enzyme MOF-based MNs showed good dependence on glucose concentration without divulging H2O2 and Co2+ ions and enough stiffness to penetrate into skin. This study offers a new strategy, using facilely synthesized MOFs as depots to integrate with MNs, for designing stimuli-responsive transdermal drug-delivery systems.

[Understanding of the theories of biaoben, genjie and qijie in the correlation with meridians and zangfu organs].

Based on the original text of Huangdi Neijing (Yellow Emperor's Internal Classic), the theories of biaoben, genjie and qijie are analyzed deeply and the practical significance is explored on the correlation with meridians and zangfu organs. Biaoben, genjie and qijie represent respectively the relevant rules between the body surface and internal organs in different patterns and they are the foundation of the multiple correlations of the upper and the lower, the internal and the external and the horizontal and the transverse between meridians and zangfu organs. The understanding above not only contributes to the recognition and the exploration of the relevant essence of meridians and zangfu organs, but also provides the theoretic guidance to the acupoint selection, diagnosis and treatment of zangfu disorders in clinical practice.

Management of Medial Collateral Ligament Insufficiency During Total Knee Arthroplasty with a Screw and Rectangular Spiked Washer: A Case Series of 14 Patients.

OBJECTIVE: To describe the technique of primary repair of medial collateral ligament (MCL) insufficiency using a screw and rectangular spiked washer in a case series of 14 patients. METHODS: Fourteen patients undergoing MCL repair by a screw and rectangular spiked washer during TKA between March 2018 and March 2019 were retrospectively reviewed. Among them, half injuries were avulsion of the femoral origin, and the other half were MCL laxity. There were 12 women and two men included in the study, with an average age of 63.6 years (range, 49-79 years) at the time of surgery. This series were followed up with a focus on range of motion (ROM), coronal alignment, Hospital for Special Surgery (HSS) knee scores, their subjective sense of joint instability, and related complications. At the last follow-up, function of the MCL was assessed by manually applying a valgus stress to the knee at both 0° and 30° of knee flexion. RESULTS: The mean follow-up time for all patients was 15.6 months (range, 13-20 months). Repair of the MCL was successful in all patients. ROM improved from a mean of 70.7° ± 35.1° before surgery to 103.9° ± 6.8° at latest follow-up (P = 0.001). All patients were able to perform a half squat easily, but none were able to do full squatting. The mean preoperative HSS score was 43.6 ± 13.4 and increased to a mean of 85.6 ± 3.8 postoperatively (P < 0.001). The femorotibial angle improved from a mean of -3.22° ± 9.47° before surgery to a mean of 5.16° ± 3.14° at the final follow-up (P = 0.006). At the time of final follow-up, no patient required revision and manipulation under anesthesia following the index arthroplasty. No radiolucencies or migration were observed in association with the knee prostheses. No displacement of the screw and rectangular spiked washer was found. There were no clinical complications. No patient reported subjective instability of the knee. Upon physical examination, no patient was found to have laxity in the coronal plane in either 30° of flexion or full extension. CONCLUSIONS: The screw and rectangular spiked washer is a simple and effective method for treating MCL sufficiency in TKA, and a study with a larger cohort and extended follow-up is requisite to claim its role in preventing coronal instability and component failure.

Poly[diaqua-(µ-oxalato)(µ-2-oxido-pyridinium-3-carboxyl-ato)praseo-dymium(III)].

In the title complex, [Pr(C(6)H(4)NO(3))(C(2)O(4))(H(2)O)(2)](n), each Pr(III) ion is coordinated by eight O atoms from two 2-oxynicotinate ligands, two oxalate ligands and two water mol-ecules, displaying a distorted bicapped square-anti-prismatic geometry. The carboxyl-ate groups link adjacent praseodymium metal centres, forming layers parallel to the bc plane. The crystal packing is stabilized by inter-molecular O-H⋯O and N-H⋯O hydrogen bonds.