Sex difference in alcohol consumption associated with colorectal cancer risk in Quzhou, China: A nested case-control study.

Objective: Colorectal cancer (CRC) incidence has been increasing worldwide over time. This study investigated whether drinking was associated with CRC risk. Methods: We designed a case-control study nested in a mass CRC screening program in Quzhou, China. Cases were newly diagnosed CRC in 2020-2022. Controls were randomly sampled using frequency match. Drinking variables included drinking status, frequency, duration, and others. Logistic regressions were used to estimate odds ratio (OR) and 95 % confidence interval (CI). Results: The crude OR (cOR) (95 % CI) of drinking between 153 cases and 650 controls was 1.46 (0.99, 2.16) in current drinkers, 3.31 (1.44, 7.60) in former drinkers, 1.82 (1.21, 2.74) in drinking 6-7 days/week, and 3.48 (1.29, 9.37) in drinking 1-19 years. Stratifying by sex, all drinking variables in women but not all in men were consistently associated with CRC risk. The adjusted OR (aOR) (95 % CI) was 1.01 (0.59, 1.74) in current drinking men, 2.27 (0.78, 6.64) in former drinking men, and 4.24 (1.61, 11.13) in current drinking women. The aOR (95 % CI) of drinking whisky was 0.19 (0.04, 0.83), 1.89 (0.86, 4.17), 2.25 (1.05, 4.83), and 1.82 (0.85, 3.92) in men drinking ≤0.5, >0.5-≤1.0, >1.0-≤1.5, and >1.5 Liter/week (P trend = 0.011), and 3.80 (1.03, 14.00) and 9.92 (2.01, 49.00) in women drinking ≤0.5 and >0.5 Liter/week (P trend = 0.001), respectively. Conclusions: There was sex difference in drinking associated with increased risk of CRC which association was stronger in women than that in men. Men's association between drinking whisky and CRC risk was J-shaped.

[Retrospective study on the diagnosis, treatment, and follow-up of 85 cases of hypophosphatemic rickets in children]. / 85ä¾‹ä½Žè¡€ç£·æ€§ä½å»ç— æ‚£å„¿è¯Šæ–­ã€æ²»ç–—ä¸Žéšè®¿çš„å›žé¡¾æ€§ç ”ç©¶.

OBJECTIVES: To study the diagnosis, treatment, and complications of hypophosphatemic rickets (HR) in children, explore effectiveness evaluation indicators for the disease, and understand the pattern in height growth among these patients. METHODS: A retrospective analysis of the initial clinical data and five-year follow-up data of 85 children with HR treated at Children's Hospital of Nanjing Medical University from January 2008 to December 2022. RESULTS: Among the 85 children with HR, there were 46 males (54%) and 39 females (46%). The age at initial diagnosis ranged from 6 months to 13 years and 9 months, with a median age of 2.75 years. The average height standard deviation score was -2.0±1.1. At initial diagnosis, children exhibited reduced blood phosphate levels and elevated alkaline phosphatase (ALP), with 99% (84/85) presenting with lower limb deformities. The positive rate for PHEX gene mutations was 93% (55/59). One year post-treatment, there was a significant reduction in ALP levels and the gap between the lower limbs (P<0.05). The fastest height growth occurred in the first year after treatment, at 8.23 cm/year, with a peak height velocity (PHV) phase lasting about two years during puberty. The height increased by 9-20 cm in male children during the PHV stage and 10-15 cm in female children. Major complications included nephrocalcinosis and hyperparathyroidism. The incidence rate of nephrocalcinosis in the first year after treatment was 55% (22/40), which increased with the duration of the disease (P<0.001); an increased urinary phosphate/creatinine ratio was positively associated with a higher risk of nephrocalcinosis (OR=1.740, P<0.001). The incidence of hyperparathyroidism in the first year after treatment was 64% (27/42). CONCLUSIONS: For children presenting with lower limb deformities, short stature, and slow growth, early testing for blood levels of phosphate, calcium, and ALP, along with imaging examinations of the lower limbs, can aid in the early diagnosis of HR. Genetic testing may be utilized for definitive confirmation when necessary. ALP combined with improvements in skeletal deformities and annual height growth can serve as indicators of therapeutic effectiveness for HR. Compared to normal children, children with HR demonstrate a lower height increase during the PHV phase, necessitating close follow-up and timely adjustment of treatment plans Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(7): 677-682.

CCDC50 mediates the clearance of protein aggregates to prevent cellular proteotoxicity.

Protein aggregation caused by the disruption of proteostasis will lead to cellular cytotoxicity and even cell death, which is implicated in multiple neurodegenerative diseases. The elimination of aggregated proteins is mediated by selective macroautophagy receptors, which is termed aggrephagy. However, the identity and redundancy of aggrephagy receptors in recognizing substrates remain largely unexplored. Here, we find that CCDC50, a highly expressed autophagy receptor in brain, is recruited to proteotoxic stresses-induced polyubiquitinated protein aggregates and ectopically expressed aggregation-prone proteins. CCDC50 recognizes and further clears these cytotoxic aggregates through autophagy. The ectopic expression of CCDC50 increases the tolerance to stress-induced proteotoxicity and hence improved cell survival in neuron cells, whereas CCDC50 deficiency caused accumulation of lipid deposits and polyubiquitinated protein conjugates in the brain of one-year-old mice. Our study illustrates how aggrephagy receptor CCDC50 combats proteotoxic stress for the benefit of neuronal cell survival, thus suggesting a protective role in neurotoxic proteinopathy.Abbreviations: AD: Alzheimer disease; ALS: amyotrophic lateral sclerosis; ATG5: autophagy related 5; BODIPY: boron-dipyrromethene; CASP3: caspase 3; CCDC50: coiled-coil domain containing 50; CCT2: chaperonin containing TCP1 subunit 2; CHX: cycloheximide; CQ: chloroquine; CRISPR: clustered regulatory interspaced short palindromic repeat; Cas9: CRISPR-associated system 9; DAPI: 4',6-diamidino-2-phenylindole; FK2: Anti-ubiquitinylated proteins antibody, clone FK2; FUS: FUS RNA binding protein; GFP: green fluorescent protein; HD: Huntington disease; HTT: huntingtin; KEGG: Kyoto Encyclopedia of Genes and Genomes; LDS: LIR-docking site; LIR: LC3-interacting region; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAPT/tau: microtubule associated protein tau; MIU: motif interacting with ubiquitin; NBR1: NBR1, autophagy cargo receptor; OPTN: optineurin; PD: Parkinson disease; PI: propidium iodide; ROS: reactive oxygen species; SOD1: superoxide dismutase 1; SQSTM1/p62: sequestosome 1; TAX1BP1: Tax1 binding protein 1; Ub: ubiquitin; UDS: UIM-docking site; UIM: ubiquitin interacting motif; UPS: ubiquitin-proteasome system.

[Value of serum fibroblast growth factor 23 in diagnosis of hypophosphatemic rickets in children]. / è¡€æ¸ æˆçº¤ç»´ç»†èƒžç”Ÿé•¿å› å­23å¯¹å„¿ç«¥ä½Žè¡€ç£·æ€§ä½å»ç— çš„è¯Šæ–­ä»·å€¼ç ”ç©¶.

OBJECTIVES: To study the value of serum fibroblast growth factor 23 (FGF23) in the diagnosis of hypophosphatemic rickets in children. METHODS: A total of 28 children who were diagnosed with hypophosphatemic rickets in Children's Hospital of Nanjing Medical University from January 2016 to June 2021 were included as the rickets group. Forty healthy children, matched for sex and age, who attended the Department of Child Healthcare of the hospital were included as the healthy control group. The serum level of FGF23 was compared between the two groups, and the correlations of the serum FGF23 level with clinical characteristics and laboratory test results were analyzed. The value of serum FGF23 in the diagnosis of hypophosphatemic rickets was assessed. RESULTS: The rickets group had a significantly higher serum level of FGF23 than the healthy control group (P<0.05). In the rickets group, the serum FGF23 level was positively correlated with the serum alkaline phosphatase level (rs=0.38, P<0.05) and was negatively correlated with maximum renal tubular phosphorus uptake/glomerular filtration rate (rs=-0.64, P<0.05), while it was not correlated with age, height Z-score, sex, and parathyroid hormone (P>0.05). Serum FGF23 had a sensitivity of 0.821, a specificity of 0.925, an optimal cut-off value of 55.77 pg/mL, and an area under the curve of 0.874 in the diagnosis of hypophosphatemic rickets (P<0.05). CONCLUSIONS: Serum FGF23 is of valuable in the diagnosis of hypophosphatemic rickets in children, which providing a theoretical basis for early diagnosis of this disease in clinical practice.

A smart and visible way to switch the aromaticity of silicon(IV) phthalocyanines.

Unlike traditional methods of modifying phthalocyanines (Pcs), we herein report a smart and visible way to switch the aromaticity of silicon(IV) phthalocyanines via a reversible nucleophilic addition reaction of the Pc skeleton induced by alkalis and acids, leading to an interesting allochroism phenomenon and the switching of photosensitive activities.

Elevated Interleukin-37 Associated with Dengue Viral Load in Patients with Dengue Fever.

Dengue remains a public health issue worldwide. Similar to chronic infectious diseases, stimulation of cytokine production is not enough to drive immune effector cells for effective virus clearance. One possible mechanism is the virus induces a large number of negative stimulatory cytokines inhibiting immune response. Interleukin 37 (IL-37) plays a crucial regulatory role in infection and immunity, inhibits innate and adaptive immunity as an anti-inflammatory cytokine by inhibiting proinflammatory mediators and pathways. To date, there are few studies reporting correlations between dengue fever (DF) and IL-37. In this study we found that the serum IL-37b and IL-37b-producing monocytes in patients were significantly increased in DF patients. A majority of the IL-37b produced by DF patients was produced by monocytes, not lymphocytes. Increased levels of IL-6, IL-10, and IFN-α were also found in DF patients. However, we failed to detect IL-1ß, IL-17A and TNF-α in plasma, because of off-target. In our study, there was no relation between IL-6, IL-10, and IFN-α expressions and IL-37b in serum (P > 0.05). The IL-37b-producing monocytes were negatively correlated with the level of IFN-α in serum and platelet count, and positively correlated with lymphocytes percentage (P < 0.05, respectively). Additionally, serum DENV nonstructural protein 1 levels were positively correlated with monocytes percentages (P < 0.05). Our data represents findings for IL-37b expression and its potential mechanisms in DF patients' immune response.

A Sulfur-Bridging Sulfonate-Modified Zinc(II) Phthalocyanine Nanoliposome Possessing Hybrid Type I and Type II Photoreactions with Efficient Photodynamic Anticancer Effects.

Phthalocyanines are potentially promising photosensitizers (PSs) for photodynamic therapy (PDT), but the inherent defects such as aggregation-caused quenching effects and non-specific toxicity severely hinder their further application in PDT. Herein, we synthesized two zinc(II) phthalocyanines (PcSA and PcOA) monosubstituted with a sulphonate group in the alpha position with "O bridge" and "S bridge" as bonds and prepared a liposomal nanophotosensitizer (PcSA@Lip) by thin-film hydration method to regulate the aggregation of PcSA in the aqueous solution and enhance its tumor targeting ability. PcSA@Lip exhibited highly efficient production of superoxide radical (O2∙-) and singlet oxygen (1O2) in water under light irradiation, which were 2.6-fold and 15.4-fold higher than those of free PcSA, respectively. Furthermore, PcSA@Lip was able to accumulate selectively in tumors after intravenous injection with the fluorescence intensity ratio of tumors to livers was 4.1:1. The significant tumor inhibition effects resulted in a 98% tumor inhibition rate after PcSA@Lip was injected intravenously at an ultra-low PcSA@Lip dose (0.8 nmol g-1 PcSA) and light dose (30 J cm-2). Therefore, the liposomal PcSA@Lip is a prospective nanophotosensitizer possessing hybrid type I and type II photoreactions with efficient photodynamic anticancer effects.

Open versus closed reduction and internal fixation in treatment of unstable pelvic fractures: a multicenter cohort study of long-term prognosis / 中华创伤骨科杂志

Objective:To compare the long-term prognosis between open versus closed reduction and internal fixation in the treatment of unstable pelvic fractures.Methods:The data of 402 consecutive patients with unstable pelvic fracture were retrospectively analyzed who had been treated at The First Medical Center and The Fourth Medical Center, PLA General Hospital, and Strategic Support Force Specialty Medical Center from March 2011 to March 2017. This cohort was divided into 2 groups according to the reduction methods. In the open group of 194 cases subjected to open reduction and internal fixation, there were 133 males and 61 females with a median age of 43.0 (30.7, 51.0) years, and 35 cases of type B and 159 cases of type C by the Tile classification. In the closed group of 208 cases subjected to closed reduction and internal fixation, there were 115 males and 93 females with a median age of 45.5 (32.0, 56.0) years, and 40 cases of type B and 168 cases of type C by the Tile classification. The 2 groups were compared in terms of 12-items Short Form Health Survey (SF-12) scores [physical component summary (PCS) and mental component summary (MCS)] at the last follow-up, time from injury to operation, frequency of intraoperative X-ray fluoroscopy, intraoperative and postoperative blood transfusion, operation time, and quality of postoperative fracture reduction.Results:There was no statistically significant difference between the 2 groups in the preoperative general data except for the gender, showing the 2 groups were comparable ( P>0.05). This cohort of 402 patients was followed up for 7.8(6.2, 8.8) years. At the last follow-up, the PCS [49.9 (45.4, 55.4) points] and MCS [53.1 (46.4, 57.6) points] in the closed group were significantly higher than those in the open group [48.2 (41.4, 52.7) and 46.5 (40.6, 53.6) points] ( P<0.05). The closed group incurred significantly shorter time from injury to operation [6 (5, 8) d] and operation time [180 (126, 260) min] than the open group [9 (6, 13) d and 240 (165, 334) min], significantly less intraoperative and postoperative blood transfusion [1.5 (0, 4.0) U] than the open group [5.0 (2.9, 8.0) U], significantly higher frequency of intraoperative X-ray fluoroscopy [104.5 (85.0, 132.0) times] than the open group [21.0 (18.0, 26.0) times], and a significantly higher excellent and good rate of postoperative fracture reduction (92.8%, 193/208) than the open group (86.6%, 168/194) (all P<0.05). Conclusion:In the treatment of patients with unstable pelvic fractures, compared with open reduction and internal fixation, closed reduction and internal fixation can not only significantly shorten the waiting time and operation time of patients, reduce the transfusion during operation, but also achieve better fracture reduction to ultimately improve the quality of life of patients.

Thermosensitive Liposomal Nanoplatform Based on Metal-Free Phthalocyanine with Copper(II)-Regulated Photoactivities.

This work reports the development of a multifunctional thermosensitive liposomal nanoplatform (PcS4 @Lip-FA) based on a metal-free phthalocyanine modified with tetra-sulfonates (PcPS4 ), which exhibited photodynamic and photothermal activities simultaneously. Upon irradiation with a near infrared laser, thermosensitive PcS4 @Lip-FA could release PcS4 as a result of the local hyperthermia of PcS4 . Interestingly, PcS4 could easily chelate with Cu2+ , leading to the enhancement of photothermal activity and decrease of photodynamic activity. In addition, in vivo fluorescence imaging revealed that PcS4 @Lip-FA could selectively accumulate in tumor tissue of H22 tumor-bearing mice after tail vein injection, and exhibited a significant anticancer phototherapeutic effect, with a tumor inhibition rate of 83.5 %. Therefore, PcPS4 @Lip-FA has realized fluorescence imaging-guided combined cancer treatment, providing a promising multifunctional nanoplatform for cancer diagnostics and therapy.

Sex differences in factors associated with neck pain among undergraduate healthcare students: a cross-sectional survey.

BACKGROUND: Neck pain is widespread among students in healthcare-related fields. Although neck pain is more prevalent in females, since most research involves mixed-sex samples we know very little about sex differences in contributors to neck pain. Thus, this study sought to explore sex differences in the risk factors for neck pain in this high-risk population. METHODS: This cross-sectional study was conducted in China in 2021 and included a sample of 1921 undergraduate healthcare students (693 males, 1228 females) from 7 health professional schools at Fujian Medical University. We collected data on neck pain symptoms, demographics, behavioral and psychological factors. Multiple regression analysis was conducted to examine sex differences in the risk factors of neck pain. RESULTS: The overall prevalence of neck pain was 41.6% with female students having a higher prevalence than male students (44.4% vs. 36.7%, respectively). The adjusted analyses showed that self-study time ≥ 6 h/day (OR = 1.44, 95% CI:1.13-1.83), flexed neck posture >20 degrees (OR = 2.19, 95% CI: 1.28-3.74), static duration posture >2 h (OR = 1.42, 95% CI: 1.02-1.97), and psychological distress (high: OR = 2.04, 95% CI:1.42-2.94; very high: OR = 2.50, 95% CI:1.57-3.74; respectively) were independent factors for neck pain in females. Among males, self-study time ≥ 6 h/day (OR = 1.43, 95% CI: 1.02-2.01) and psychological distress (moderate: OR = 2.04, 95% CI:1.28-3.25; high: OR = 2.37, 95% CI:1.49-3.79; very high: OR = 2.97, 95% CI:1.75-5.02; respectively) were significant risk factors for neck pain. CONCLUSIONS: These findings suggest that the risk profiles of neck pain differ between females and males. The modifiable risk factors for neck pain, such as prolonged self-study time and elevated psychological distress, as well as poor posture among females, could be targeted through health promotion interventions in university settings.

Molecular and Supramolecular Approach to Highly Photocytotoxic Phthalocyanines with Dual Cell Uptake Pathways and Albumin-Enhanced Tumor Targeting.

Phototherapy for non-invasive cancer treatment has been extensively studied. An urgent challenge in phototherapy application is to fabricate appropriate targeted agents to achieve efficient therapeutic effect. Herein, a molecular and supramolecular approach for targeting phototherapy was reasonably designed and realized through the axial sulfonate modification of silicon(IV) phthalocyanines (Pcs), followed by supramolecular interaction with albumin. This approach can not only improve the photoactivities (e.g., fluorescence emission and reactive oxygen species production) of the Pcs but also enhance their tumor targeting. Most importantly, one of the deigned Pcs (4) can target HepG2 cells through dual cell pathways, leading to an extremely high phototoxicity with an EC50 (i.e., concentration of Pcs to kill 50% of cells under light irradiation) value of 2.0 nM. This finding presents a feasible strategy to realize efficient targeting phototherapy.

Aggregation-Enhanced Sonodynamic Activity of Phthalocyanine-Artesunate Conjugates.

The clinical prospect of sonodynamic therapy (SDT) has not been fully realized due to the scarcity of efficient sonosensitizers. Herein, we designed phthalocyanine-artesunate conjugates (e.g. ZnPcT4 A), which could generate up to ca. 10-fold more reactive oxygen species (ROS) than the known sonosensitizer protoporphyrin IX. Meanwhile, an interesting and significant finding of aggregation-enhanced sonodynamic activity (AESA) was observed for the first time. ZnPcT4 A showed about 60-fold higher sonodynamic ROS generation in the aggregated form than in the disaggregated form in aqueous solutions. That could be attributed to the boosted ultrasonic cavitation of nanostructures. The level of the AESA effect depended on the aggregation ability of sonosensitizer molecules and the particle size of their aggregates. Moreover, biological studies demonstrated that ZnPcT4 A had high anticancer activities and biosafety. This study thus opens up a new avenue the development of efficient organic sonosensitizers.

Nanostructured Phthalocyanine Assemblies with Efficient Synergistic Effect of Type I Photoreaction and Photothermal Action to Overcome Tumor Hypoxia in Photodynamic Therapy.

Most photodynamic therapy (PDT) paradigms work through the highly O2-dependent type II photoreaction to generate singlet oxygen (1O2). The hypoxic microenvironment of solid tumors severely hampers therapeutic outcomes. Here, we present a novel design that could transfer the photophysical and photochemical properties of traditional phthalocyanine-based photosensitizers from type II photoreaction to efficient type I photoreaction and vibrational relaxation-induced photothermal conversion. These features enable the obtained nanostructured phthalocyanine assemblies (e.g., NanoPcAF) to display excellent phototherapies under both normoxic and hypoxic conditions. Moreover, NanoPcAF has a high level of accumulation in tumor tissues after intravenous injection, and 94% of tumor growth is inhibited in a preclinical model at a NanoPcAF dose of 0.8 nmol g-1 and light dose of 300 J cm-2.

CDH11 Regulates Adhesion and Transcellular Migration of Tongue Squamous Cell Carcinoma.

PURPOSE: CDH11, as a member of cadherins, mediates homotypic cell adhesion. Some studies have shown that CDH11 plays an important role in the development of tumors, especially in the processes of tumor invasion and metastasis. While features of CDH11 in tongue squamous cell carcinoma (TSCC) are still indeterminate, the purpose of the present study is to explore the role of CDH11 in TSCC. METHODS: The expression of cadherin gene in a TSCC cell line with high metastatic potential (LN4) and the parental CAL27 were examined both in the TCGA database and in collected clinical samples, further verified by quantitative real-time PCR. The effects of CDH11 on the proliferation, apoptosis, migration, invasion and adhesion were tested in appropriate ways after CDH11 was overexpressed in TSCC cells. RESULTS: Among the 22 cadherin genes, CDH11 was one of the most obviously inhibited genes in LN4 cells as compared with the parental cells. Overexpression of CDH11 did not show a significant effect on cell proliferation, apoptosis, stemness, migration and invasion ability of TSCC cells themselves, but it increased the adhesion of TSCC cells with human oral epithelial cells and decreased their ability to pass through human oral epithelial cells (HOECs) for migration. CONCLUSION: The results indicated that CDH11 plays as a tumor suppressor in tongue squamous cell carcinoma by inhibiting the invasion and migration of tongue cancer cells. CDH11 may serve as an effective clinical target for new tongue cancer treatments.

Effect of Pharmacological Inhibition of Fat-Mass and Obesity-Associated Protein on Nerve Trauma-Induced Pain Hypersensitivities.

Genetic knockout or knockdown of fat-mass and obesity-associated protein (FTO), a demethylase that participates in RNA N6-methyladenosine modification in injured dorsal root ganglion (DRG), has been demonstrated to alleviate nerve trauma-induced nociceptive hypersensitivities. However, these genetic strategies are still impractical in clinical neuropathic pain management. The present study sought to examine the effect of intrathecal administration of two specific FTO inhibitors, meclofenamic acid (MA) and N-CDPCB, on the development and maintenance of nociceptive hypersensitivities caused by unilateral L5 spinal nerve ligation (SNL) in rats. Intrathecal injection of either MA or N-CDPCB diminished dose-dependently the SNL-induced mechanical allodynia, heat hyperalgesia, cold hyperalgesia, and spontaneous ongoing nociceptive responses in both development and maintenance periods, without altering acute/basal pain and locomotor function. Intrathecal MA also reduced the SNL-induced neuronal and astrocyte hyperactivities in the ipsilateral L5 dorsal horn. Mechanistically, intrathecal injection of these two inhibitors blocked the SNL-induced increase in the histone methyltransferase G9a expression and rescued the G9a-controlled downregulation of mu opioid receptor and Kv1.2 proteins in the ipsilateral L5 DRG. These findings further indicate the role of DRG FTO in neuropathic pain and suggest potential clinical application of the FTO inhibitors for management of this disorder.

Circular RNA TRAPPC6B inhibits intracellular Mycobacterium tuberculosis growth while inducing autophagy in macrophages by targeting microRNA-874-3p.

OBJECTIVES: Genetic and epigenetic mechanisms regulate antimicrobial immunity against Mycobacterium tuberculosis (Mtb) infection. METHODS: The present study assessed circular RNA TRAPPC6B (circTRAPPC6B) for antimicrobial immune functions and defined mechanisms wherein circTRAPPC6B regulates Mtb growth, autophagy and microRNA in macrophages. RESULTS: The Mtb infection of monocytes/macrophages resulted in a significantly decreased level of circTRAPPC6B that inhibited intracellular Mtb growth in macrophages. Conversely, circTRAPPC6B expression enhanced autophagy or autophagy-associated protein LC3-II production in Mtb-infected macrophages. circTRAPPC6B-enhanced autophagy aggregation or sequestration was also observed in fluorescence in situ hybridisation (FISH) analysis and confocal imaging. Mechanistically, circTRAPPC6B targets an inhibiting element miR-874-3p, as shown by bioinformatics, dual-luciferase reporter gene analysis and pull-down assay, respectively. Notably, miR-874-3p prohibited autophagy via suppressing autophagy protein ATG16L1 by binding to its 3'-untranslated region (UTR) in Mtb-infected macrophages and thus promoting intracellular Mtb growth. Concurrently, circTRAPPC6B enhanced autophagy in Mtb-infected macrophages by blocking the ability of miR-874-3p to inhibit ATG16L1. Thus, circTRAPPC6B antagonises the ability of miR-874-3p to suppress ATG16L1 expression and activate and enhance autophagy sequestration to restrict Mtb growth in macrophages. CONCLUSION: The current findings suggested that both circTRAPPC6B and miR-874-3p mechanisms can be explored as potential therapeutics against Mtb infection.

A pH-sensitive nanoagent self-assembled from a highly negatively-charged phthalocyanine with excellent biosafety for photothermal therapy.

Photothermal therapy (PTT) is a promising strategy for cancer treatment. However, the development of highly efficient photothermal agents with excellent biosafety, particularly with low liver retention, is very meaningful for clinical applications, but it is also challenging. We herein prepared a pH-sensitive nanoagent (NanoPc3) by the self-assembly of a zinc(ii) phthalocyanine substituted with hexadeca-sulphonates linked by hydrazone bonds for photoacoustic imaging and PTT. Due to the highly negative surface potential (-30.80 mV in water), NanoPc3 could effectively escape the phagocytosis of the reticuloendothelial system and be rapidly cleared from normal tissues, leading to little accumulation in the liver and excellent biosafety. The highly negatively-charged NanoPc3 changed into nearly neutral nanoparticles (NanoPc3H) under slightly acidic conditions, resulting in enhanced cellular uptake and retention time in tumor tissues. Moreover, the tumor of H22 tumor-bearing mice treated with NanoPc3 almost disappeared, suggesting an outstanding photothermal antitumor effect. NanoPc3 also hardly showed skin phototoxicity under irradiation. Its excellent antitumor effect and biosafety make NanoPc3 highly promising in clinical applications. This work will provide a new strategy for the design of tumor-targeted photothermal nanoagents with high biosafety.

Regulation of the expression of proinflammatory cytokines induced by SARS-CoV-2.

An outbreak of a novel coronavirus was reported in Wuhan, China, in late 2019. It has spread rapidly through China and many other countries, causing a global pandemic. Since February 2020, over 28 countries/regions have reported confirmed cases. Individuals with the infection known as coronavirus disease-19 (COVID-19) have similar clinical features as severe acute respiratory syndrome first encountered 17 years ago, with fever, cough, and upper airway congestion, along with high production of proinflammatory cytokines (PICs), which form a cytokine storm. PICs induced by COVID-19 include interleukin (IL)-6, IL-17, and monocyte chemoattractant protein-1. The production of cytokines is regulated by activated nuclear factor-kB and involves downstream pathways such as Janus kinase/signal transducers and activators transcription. Protein expression is also regulated by post-translational modification of chromosomal markers. Lysine residues in the peptide tails stretching out from the core of histones bind the sequence upstream of the coding portion of genomic DNA. Covalent modification, particularly methylation, activates or represses gene transcription. PICs have been reported to be induced by histone modification and stimulate exudation of hyaluronic acid, which is implicated in the occurrence of COVID-19. These findings indicate the impact of the expression of PICs on the pathogenesis and therapeutic targeting of COVID-19.

A phthalocyanine-based self-assembled nanophotosensitizer for efficient in vivo photodynamic anticancer therapy.

To develop highly efficient photosensitizers for photodynamic therapy, herein a zinc(II) phthalocyanine-folate conjugate (PcN-FA) used to construct an activatable nanophotosensitizer (NanoPcN-FA) through a facile self-assembly. The self-assembled nanophotosensitizer (NanoPcN) without folate-modification was used as a negative control. After self-assembly, the photoactivities of NanoPcN-FA was quenched. The in vitro studies showed that NanoPcN-FA could be taken in by folate-receptor (FR)-positive SKOV3 cells and activated in the cells. It also exhibited slightly higher photocytotoxicity against SKOV3 cells than NanoPcN. Moreover, the competitive assay confirmed that the cellular uptake of NanoPcN-FA was through a FR-mediated process. Finally, the in vivo results indicated that NanoPcN-FA could target tumor tissue of S180 rat ascitic tumor-bearing mice due to the folic acid (FA) ligand, leading to a highly efficient antitumor photodynamic efficacy with the tumor inhibition rate of 95%.