Efficacy and safety of microbial transglutaminase-induced scleral stiffening invivo.

The purpose of this study was to investigate the efficacy and safety of microbial transglutaminases (mTGases) during scleral collagen cross-linking (CXL) in vivo. Sixteen New Zealand white albino rabbits were treated with sub-Tenon's injections of 2 ml of 1 U/ml mTGases in the right eye and 2 ml of phosphate buffer saline (PBS) in the left eye. The rabbits were killed 2 weeks after the injection, and all eyeballs, including some scleral strips, were processed. The elastic modulus was measured with a biomaterials tester. Histopathological analysis and transmission electron microscopy (TEM) were used for the morphological observations. The elastic modulus of the mTGase-treated sclera was 15.79 ± 2.93 MPa, and that of the control was 6.91 ± 2.23 MPa, indicating an increase of 129% after the mTGases treatment (P < 0.05). The density of the scleral collagen bundles and diameter of the collagen fibrils increased compared with those in the control group. No apoptosis was detected in the retina or posterior sclera by TUNEL staining, and no histological damage was observed on the TEM scan. This study is based on a short-term study on animal models. These results indicate that mTGase-mediated scleral CXL is a promising approach to effectively stiffen the sclera and safe enough for retina, and may be a useful treatment modality for strengthening scleral tissue.

Experimental evidence to understand mechanical causes of retinal detachment following blunt trauma.

PURPOSE: This study aimed to perform an in vitro experiment to simulate retinal detachment caused by blunt impact, and provide experimental evidence to understand mechanical causes of traumatic retinal detachment. METHODS: The experiment was conducted on twenty-two fresh porcine eyes using a bespoke pendulum testing device at two energy levels (0.1J for low energy and 1.0J for high energy). We examined dynamic forces and mechanical responses to the impact, including global deformations, intraocular pressure changes and the energy absorption. Another set of twenty-two eyes underwent pathological examination immediately after being subjected to blunt impact. Twelve additional intact eyes were examined as controls. All pathological sections were scored to indicate whether retinal detachment had occurred. RESULTS: A dynamic variation in intraocular pressure was detected following impact and exhibited an approximate sinusoidal oscillation-attenuation profile. The peaks of impact force were 12.9 ± 1.9 N at low-energy level and 34.8 ± 9.8 N at high-energy level, showing a significant difference (p < 0.001). The positive and negative peaks of intraocular pressure were 149.4 ± 18.9 kPa and -10.9 ± 7.2 kPa at low-energy level, and 274.5 ± 55.2 kPa and -35.7 ± 23.7 kPa at high-energy level, showing significant differences (p < 0.001 for both levels). Retinal detachments were observed in damaged eyes while few detachments were found in control eyes. The occurrence rate of retinal detachment differed significantly (p < 0.05) between the high- and low-energy impact groups. CONCLUSIONS: This study provided experimental evidence that shockwaves produced by blunt trauma break the force equilibrium and lead to the oscillation and negative pressure, which mainly contribute to traumatic retinal detachment.

Linear Peptide-Based PET Tracers for Imaging PD-L1 in Tumors.

Programmed cell death receptor 1 (PD-1) and its ligand PD-L1 are particularly interesting immune checkpoint proteins for human cancer treatment. Positron emission tomography (PET) imaging allows for the dynamic monitoring of PD-L1 status during tumor progression, thus informing patients' response index. Herein, we report the synthesis of two linear peptide-based radiotracers, [64Cu]/[68Ga]HKP2201 and [64Cu]/[68Ga]HKP2202, and validate their utility for PD-L1 visualization in preclinical models. The precursor peptide HKP2201 was derived from a linear peptide ligand, CLP002, which was previously identified by phage display and showed nanomolar affinity toward PD-L1. Appropriate modification of CLP002 via PEGylation and DOTA conjugation yielded HKP2201. The dimerization of HKP2201 generated HKP2202. The 64Cu and 68Ga radiolabeling of both precursors was studied and optimized. PD-L1 expression in mouse melanoma cell line B16F10, mouse colon cancer cell line MC38, and their allografts were assayed by immunofluorescence and immunohistochemistry staining. Cellular uptake and binding assays were conducted in both cell lines. PET imaging and ex vivo biodistribution studies were employed in tumor mouse models bearing B16F10 and MC38 allografts. [64Cu]/[68Ga]HKP2201 and [64Cu]/[68Ga]HKP2202 were obtained with satisfactory radiocharacteristics. They all showed lower liver accumulation compared to [64Cu]/[68Ga]WL12. B16F10 and MC38 cells and their tumor allografts sections were verified to express PD-L1. These tracers demonstrated a concentration-dependent cell affinity and a comparable half-maximal effect concentration (EC50) with radiolabeled WL12. Competitive binding and blocking studies demonstrated the specific target of these tracers to PD-L1. PET imaging and ex vivo biodistribution studies revealed notable tumor uptake in tumor-bearing mice and rapid clearance from blood and major organs. Importantly, [64Cu]/[68Ga]HKP2202 showed higher tumor uptake compared to [64Cu]/[68Ga]HKP2201. Of note, [64Cu] labeled tracers showed longer retention in tumors than [68Ga] labeled traces, indicating advantages in the long-term tracking of PD-L1 dynamics. In comparison, [68Ga]HKP2201 and [68Ga]HKP2202 showed lower liver accumulation, enabling its great potential in the fast detection of both primary and metastatic tumors, including hepatic carcinoma. [64Cu]/[68Ga]HKP2201 and [64Cu]/[68Ga]HKP2202 are promising PET tracers for visualizing PD-L1 status. Notably, their combination would cooperate in rapid diagnosis and subsequent treatment guidance. Future assessment of the radiotracers in patients is needed to fully evaluate their clinical value.

Assessment of peripapillary retinal nerve fiber layer thickness and vessel density in newly diagnosed SLE patients without ocular symptoms.

PURPOSE: This study aims to assess peripapillary retinal nerve fiber layer thickness (pRNFLT) and peripapillary vessel density (PVD) in patients with newly diagnosed active and inactive systemic lupus erythematosus (SLE) by optical coherence tomography (OCT) and OCT angiography (OCTA). METHODS: This is a cross-sectional study, in which 77 newly diagnosed SLE patients without ocular symptoms (including 36 active SLE patients and 41 inactive SLE patients) and 72 age- and gender-matched healthy subjects were recruited. All participants underwent OCT and OCTA to evaluate pRNFLT, PVD, and radial peripapillary capillary density (RPCD), respectively. Clinical data at the time of initial diagnosis of SLE, including erythrocyte, leukocyte, platelet, albumin-globulin ratio, erythrocyte sedimentation rate, C-reactive protein, serum complement 3, serum complement 4, anti-dsDNA antibody, and 24-h proteinuria, were collected. RESULTS: No difference was found in pRNFLT between active SLE patients, and healthy controls, average pRNFLT, superonasal RNFLT, and inferonasal pRNFLT were reduced in inactive SLE patients than in healthy controls (p≤0.008). Temporal PVD, inferotemporal PVD, and inferotemporal RPCD in active SLE patients were significantly lower than those in healthy controls (p≤0.043). There also was a trend towards lower temporal RPCD in active SLE than healthy controls (p=0.089). Average PVD, average RPCD, superonasal RPCD, inferonasal RPCD, and inferotemporal RPCD were decreased in inactive SLE patients than in healthy controls (p≤0.047). Additionally, inferotemporal RPCD in active SLE patients was positively associated with albumin-globulin ratio (p=0.041). Temporal RPCD was negatively correlated with anti-dsDNA antibody (p=0.012) and 24-h proteinuria (p=0.006). CONCLUSIONS: PRNFL and PVD damage existed in newly diagnosed SLE patients without ocular symptoms. Temporal and inferotemporal RPCD were associated with the laboratory indicators of impaired renal function in active SLE patients, respectively.

Design and Synthesis of Novel Celastrol Derivatives as Potential Anticancer Agents against Gastric Cancer Cells.

Gastric cancer (GC) is a common malignant disease worldwide, and finding novel agents and strategies for the treatment of GC are of urgent need. Celastrol (CEL) is a well-known natural product with antineoplastic activity. In this study, pyrazole analogues were introduced at the C-29 position of CEL. A total of 24 new derivatives were designed, synthesized, and evaluated for their mechanism and antitumor activity in vitro and in vivo. Among them, compound 21 exhibited the best activity against BGC-823 cells (IC50 = 0.21 ± 0.01 µM). Further biological studies showed that 21 significantly raised the reactive oxygen species (ROS) levels to activate the apoptotic pathway, causing mitochondrial dysfunction in BGC-823 cells. In addition, 21 also arrested cells in the G2/M phase to induce tumor cell apoptosis. In a nude mouse tumor xenograft model, 21 exhibited a better tumor inhibition rate (89.85%) than CEL (inhibition rate 76.52%). Taken together, the present study has provided an anticancer lead compound candidate, 21, and has revealed that increased ROS generation may be an effective strategy in the treatment of GC.

Effect of enzyme-induced collagen crosslinking on porcine sclera.

This study aims to evaluate the effect of a new type of collagen crosslinking (CXL) mediated by microbial transglutaminases (Tgases) on sclera. Porcine eyes were divided into two groups according to the different crosslinking procedures used: the double-sided CXL group (D-CXL group) and the single-sided CXL group (S-CXL group). In the D-CXL group, 4.0 × 14.0 mm scleral strips harvested from 40 porcine eyeballs were incubated with 1 U/ml Tgases for 30 min at 37 °C. Parallel scleral strips from the same eyeball were incubated with PBS under the same conditions as the controls. In the S-CXL group, 80 whole globes were directly incubated with 1 U/ml Tgases and PBS as the controls for 30 min at 37 °C. After incubation, 4.0 × 14.0 mm scleral strips were cut from each eyeball. Biomechanical testing and light microscopy were used. In the D-CXL group, the general elastic modulus of the Tgases-treated scleral strips was 14.89 ± 6.05 MPa, and the controls was 6.72 ± 2.58 MPa, indicating an increase of 121% with Tgases treatment. In the S-CXL group, the general elastic modulus of the Tgases-treated scleral strips was 12.88 ± 4.29 MPa, and the controls was 7.00 ± 2.45 MPa, indicating an increase of 84% with Tgases treatment. In both the D-CXL and S-CXL groups, significant increases in scleral rigidity were observed compared to that of the respective controls (P < 0.05). The histology indicated increased collagen bundle density, decreased interfibrillar spaces and increased interlamellar spaces after CXL. In conclusion, scleral collagen crosslinking mediated by Tgases produced a significant increase in biomechanical strength.

Novel chromanone-dithiocarbamate hybrids as multifunctional AChE inhibitors with ß-amyloid anti-aggregation properties for the treatment of Alzheimer's disease.

By connecting chromanone with dithiocarbamate moieties through flexible linkers, a series of hybrids as novel multifunctional AChE inhibitors have been designed and synthesized. Most of these compounds displayed strong and excellently selective inhibition to eeAChE as well as potent inhibition to self- and AChE-induced Aß aggregation. Among them, compound 6c showed the best activity to inhibit eeAChE (IC50 = 0.10 µM) and AChE-induced Aß aggregation (33.02% at 100 µM), and could effectively inhibit self-induced Aß aggregation (38.25% at 25 µM). Kinetic analysis and docking study indicated that compound 6c could target both the CAS and PAS, suggesting that it was a dual binding site inhibitor for AChE. Besides, it exhibited good ability to penetrate the BBB and low neurotoxicity in SH-SY5Y cells. More importantly, compound 6c was well tolerated in mice (2500 mg/kg, po) and could attenuate the memory impairment in a scopolamine-induced mouse model. Overall, these results highlight 6c as a promising multifunctional agent for treating AD and also demonstrate that the dithiocarbamate is a valid scaffold for design of multifunctional AChE inhibitors.

Survey of Traveler's Diarrhea: Epidemiology and Testing Reveal the Source.

OBJECTIVE: To understand the causes and transmission routes of, as well as risk factors, for a Salmonella outbreak in a tour group. METHOD: A retrospective cohort design was used to conduct an epidemiological field investigation. Real-time fluorescent quantitative PCR, bacterial culture, and serological identification methods were used for pathogen detection and identification. RESULT: There were 7 cases of illness, and the attack rate was 46.67%. The onset date was concentrated on May 9 and 10. All cases were found in the tour group, and no cases occurred in the nontour group. The results of this retrospective cohort study showed that the consumption of boiled eggs for breakfast on May 9 was a common factor (R 2 = 6.67, P=0.023). Salmonella enteritidis was identified from the patients' stool and vomit. CONCLUSION: The food poisoning epidemic was caused by Salmonella enteritidis. In the summer and autumn, attention should be paid to preservation, processing, and cooking of food to avoid bacterial contamination. To prevent sickness, travelers should know the disease prevalence at their destinations in advance.

Diphenylamine-Substituted Osmanaphthalyne Complexes: Structural, Bonding, and Redox Properties of Unusual Donor-Bridge-Acceptor Systems.

Diarylamine-substituted osmanaphthalyne complexes that feature two redox centers linked by the rigid skeleton of the metallacycle (C^C+ ), specifically, [OsCl2 (PPh3 )2 {(C^C+ )NAr2 }][BF4 - ] (Ar=Ph (1 a), p-MeOPh (1 b)) and their open-ring precursors [OsHCl2 (PPh3 )2 {(≡C-C(PPh3 + )=CHPh)NR2 }][BF4 - ] (Ar=Ph (2 a), p-MeOPh (2 b)), were successfully synthesized and characterized by 1 H, 13 C, and 31 P NMR spectroscopy, ESI-MS, and elemental analysis. The solid-state molecular structures of complexes 1 a and 2 a were ascertained by single-crystal X-ray diffraction. The Os≡C bond length in both complexes 1 a and 2 a fell within the range reported for similar osmanaphthalynes and osmium carbyne complexes, respectively. The structural parameters determined for complex 1 a, which were successfully reproduced by theoretical calculations, point to a π-delocalized metallacycle structure. The purple color of compounds 1 a and b was explained by the diarylamine→Os(metallacycle) charge-transfer absorption in the visible region. The neutral, one-electron-oxidized and one-electron-reduced states of compounds 1 a, b, and a reference complex that lacked the diarylamine substituent, [OsCl2 (PPh3 )2 {(C^C+ )}][BF4 - ] (1'), were investigated by cyclic and square-wave voltammetry, UV/Vis/NIR spectroelectrochemistry, and DFT calculations. The spin density in singly oxidized complexes [1 a]+ and [1 b]+ predominantly resided on the aminyl segment, with osmium involvement controlled by the diphenylamine substitution. Spin density in stable, singly-reduced [1']- was distributed mainly over the osmanaphthalyne metallacycle.

[Effects on expression of osteogenesisgene in the osteoblast with endoplasmic reticulum stress induced by fluoride].

OBJECTIVE: To explore the gene expressions of endoplasmic reticulum stress and differentiation in osteoblast treated by excess fluoride. METHODS: Using primary cultured human osteoblasts for fluorosis model in vitro, apoptosis was inspected by flow cytometer, and RNA was extracted for examination of the unfolded protein response and bone differentiation genes. RESULTS: Fluoride could cause endoplasm reticulum stress in osteoblasts by 15 genes upregulated, 1 gene downregulated. These genes involved PERK, IRE1 and ATF6 signaling pathways of endoplasmic reticulum stress. Meanwhile 32 osteogenesis genes were upregulated, and 2 genes downregulated, involving collagen, matrix metalloproteinase, integrin, bone morphogenetic protein, vascular endothelial growth factor, and tumor necrosis factor gene. CONCLUSION: Excess fluoride can cause endoplasmic stress in osteoblast, while have an impact on the gene expression of osteogenesis.

Vernodalin Alleviates Cardiotoxicity and Inflammation in Isoproterenol-Mediated Myocardial Infarction through NF-κB/AMPK Signaling Pathways in Rats.

BACKGROUND: Myocardial infarction (MI) is the foremost cause of mortality in cardiovascular diseases. MI ultimately exacerbates cardiotoxicity due to the release of toxicity biomarkers and inflammatory infiltration. AIM: Vernodalin (VN) is a renowned cytotoxic sesquiterpene lactone that possesses antioxidant, anticancer, and anti-inflammatory properties. The cardioprotective mechanism of VN remains concealed. Hence, we explored the cardioprotective efficacy of VN on isoproterenol (ISO)- mediated MI and analyzed its underlying mechanism. METHODS: Wistar albino rats were injected ISO (85 mg/kg bw) subcutaneously to induce MI to evaluate the cardioprotective potential of VN (10 mg/kg bw) by assessing heart weight/ body weight index, hemodynamic, toxicity enzymes, histopathology, inflammatory mediators, and signaling pathway. ISO enhanced heart weight/body weight index, cardiotoxicity enzymes, biomarkers, inflammation, and histopathological changes while reducing hemodynamic parameters and VEGF-B, AMPK, and eNOS signaling pathways. RESULTS: Treatment with VN could significantly (p<0.05) mitigate the heart weight/body weight index, cardiotoxicity enzymes, biomarkers, inflammatory cytokines, and histopathological changes while enhancing hemodynamic parameters and VEGF-B, AMPK, and eNOS signaling pathways. Collectively, our findings revealed that the VN ameliorated defensive action against MI and averted myocardial injury by reducing the NF-κB-mediated inflammatory pathways in rats. CONCLUSION: These findings established that VN expressively preserves the myocardium and employs anti-inflammatory actions by regulating NF-κB, VEGF-B, AMPK, and eNOS signaling pathways.

Association between dietary vitamin A intake from different sources and non-alcoholic fatty liver disease among adults.

Non-alcoholic fatty liver disease (NAFLD) has become an urgent public health issue with high global prevalence, but data on NAFLD are inconsistent. The association of total dietary vitamin A intake with the NAFLD risk was not well documented in previous studies. To explore the relationship between dietary vitamin A intake from different sources and NAFLD risk among American adults. Data were collected from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2014. Logistic regression and restricted cubic spline models were used to estimate the relationship between total dietary vitamin A intake and NAFLD risk. 6,613 adult participants were included. After adjusting potential confounders, the odds ratios (ORs) with 95% confidence intervals (CIs) of NAFLD for the highest quartile intake of total vitamin A, preformed vitamin A, provitamin A carotenoids were respectively 0.86 (0.69-1.06), 0.97 (0.74-1.28), and 0.78 (0.61-0.99), compared to the lowest quartile. Stratifying gender and age, provitamin A carotenoids intake was inversely associated with NAFLD risk in females and participants aged < 45 years. Dose-response analysis indicated a linear negative relationship between provitamin A carotenoids intake and NAFLD risk. Provitamin A carotenoids intake was inversely associated with NAFLD, especially in women and those aged < 45 years among adult American.

Orally administrated fucoidan and its low-molecular-weight derivatives are absorbed differentially to alleviate coagulation and thrombosis.

Thrombosis is a serious threat to human health and life. Fucoidan, a sulfated polysaccharide from brown algae, could prevent coagulation and thrombus after intravenous administration. However, more efforts are still needed to develop its oral agent. In the present study, the absorption and excretion of fucoidan (90.8 kDa) and its degradation products, Dfuc1 (19.2 kDa) and Dfuc2 (5.5 kDa), were determined by HPLC-MS/MS after acid degradation and 1-phenyl-3-methyl-5-pyrazolone derivatization, and their anticoagulation and antithrombotic activities were evaluated in vivo after oral administration. Results showed that the maximum concentrations of fucoidan, Dfuc1 and Dfuc2 in rat plasma all achieved at 2 h after oral administration (150 mg/kg), and they were 41.1 ± 10.6 µg/mL, 45.3 ± 18.5 µg/mL and 59.3 ± 13.7 µg/mL, respectively. In addition, fucoidan, Dfuc1 and Dfuc2 could all prolong the activated partial thromboplastin time in vivo from 23.7 ± 2.7 s (blank control) to 25.1 ± 2.6 s, 27.1 ± 1.7 s and 29.4 ± 3.6 s, respectively. Moreover, fucoidan and its degradation products showed similar antithrombotic effect in carrageenan-induced thrombosis mice, and untargeted metabolomics analysis revealed that they all markedly regulated the carrageenan-induced metabolite disorders, especially the arachidonic acid metabolism. Thus, the degradation products of fucoidan with lower molecular weights are more attractive for the development of oral antithrombotic agents.

Beyond Small Molecules: Antibodies and Peptides for Fibroblast Activation Protein Targeting Radiopharmaceuticals.

Fibroblast activation protein (FAP) is a serine protease characterized by its high expression in cancer-associated fibroblasts (CAFs) and near absence in adult normal tissues and benign lesions. This unique expression pattern positions FAP as a prospective biomarker for targeted tumor radiodiagnosis and therapy. The advent of FAP-based radiotheranostics is anticipated to revolutionize cancer management. Among various types of FAP ligands, peptides and antibodies have shown advantages over small molecules, exemplifying prolonged tumor retention in human volunteers. Within its scope, this review summarizes the recent research progress of the FAP radiopharmaceuticals based on antibodies and peptides in tumor imaging and therapy. Additionally, it incorporates insights from recent studies, providing valuable perspectives on the clinical utility of FAP-targeted radiopharmaceuticals.

Multiple roles of ferric chloride in preparing efficient magnetic hydrochar for sorption of methylene blue from water solutions.

Highly efficient and cheap magnetic materials have application prospects in wastewater treatment. Herein, Fe3O4-loaded hydrochar (HC-Fe3O4) was obtained from hydrothermal carbonization (HTC) of bamboo with FeCl3 and then added with FeCl3 to form a magnetic sorbent via simple precipitation. The HC-Fe3O4 was characterized with various instruments. The characterizations show FeCl3 plays at least two roles as a catalyst and an oxidant in HTC. The specific surface area of hydrochar enlarged from 39.9731 to 60.9887 m2·g-1 after the addition of FeCl3 during HTC, which showed FeCl3 acted as a catalyst in HTC. XRD indicated Fe3O4 was formed by the structure of HC-Fe3O4, which indicated Fe(III) was reduced to Fe(II) during HTC. Sorption of methylene blue (MB) onto HC-Fe3O4 was better fitted by the Langmuir isotherm and pseudo-second-order kinetic models. Sorption is a spontaneous thermodynamic endothermic process and HC-Fe3O4 is easily separated by an applied magnetic field and reused.

H2O2-TiO2 photocatalytic degradation of chondroitin sulfate and in vivo absorption and excertion of its product.

Chondroitin sulfate (CS) is widely known for its various biological activities which are closely related to the sulfate substitution and the molecular weight. Effective degradation methods without striping sulfate groups are in a need. In the present study, a photocatalytic degradation method using H2O2 and TiO2 has been developed and it could decrease the average molecular weight of CS into 5 kDa within 6 h. The chemical composition of CS before and after degradation were compared by FT-IR, NMR, etc., and no removement of sulfate group was observed. Then the identification of the oligosaccharides in the degradation product by mass spectroscopy revealed that glucuronic acid or its derivative, arabinuronic acid, was at most of the reducing ends, and the depolymerization mechanism was proposed. Furthermore, the absorption of CS in rats was enhanced by the degradation while the excertion profile of the degradation product was similar to that of CS.

Inhibitory effects of fucoidan from Laminaria japonica against some pathogenic bacteria and SARS-CoV-2 depend on its large molecular weight.

Fucoidan is a highly sulfated polysaccharide with a wide range of bioactivities, including anti-pathogenic activity. However, the relationship between structure and activity of fucoidan in inhibiting pathogen infections remains unclear. Here, different-molecular-weight fucoidans were prepared by photocatalytic degradation followed by membrane ultrafiltration, and their chemical structures and anti-pathogenic microbiota activity were compared. Results showed that photocatalytic degradation could effectively degrade fucoidan while its structure block and sulfate groups were not destroyed obviously. Fucoidan (90.8 kDa) of 5 mg/mL could inhibit the growth of S. aureus, S. typhimurium and E. coli, but its degradation products, Dfuc1 (19.2 kDa) and Dfuc2 (5.5 kDa), demonstrated lower inhibitory effect. In addition, compared to Dfuc1 and Dfuc2, fucoidan showed stronger capability to prevent the adhesion of S. aureus, L. monocytogenes, V. parahaemolyticus and S. typhimurium to HT-29 cells. Moreover, the inhibitory effect against SARS-CoV-2 and the binding activity to S protein were also positively correlated to molecular weight. These results indicate that natural fucoidan with higher molecular weight are more effective to inhibit these pathogenic bacteria and SARS-CoV-2, providing a better understanding of the relationship between structure and activity of fucoidan against pathogenic microbiota.

Controllable Synthesis of 2H-1T' Mox Re(1- x ) S2 Lateral Heterostructures and Their Tunable Optoelectronic Properties.

Constructing heterostructures and doping are valid ways to improve the optoelectronic properties of transition metal dichalcogenides (TMDs) and optimize the performance of TMDs-based photodetectors. Compared with transfer techniques, chemical vapor deposition (CVD) has higher efficiency in preparing heterostructures. As for the one-step CVD growth of heterostructures, cross-contamination between the two materials may occur during the growth process, which may provide the possibility of one-step simultaneous realization of controllable doping and formation of alloy-based heterostructures by finely tuning the growth dynamics. Here, 2H-1T' Mox Re(1- x ) S2 alloy-to-alloy lateral heterostructures are synthesized through this one-step CVD growth method, utilizing the cross-contamination and different growth temperatures of the two alloys. Due to the doping of a small amount of Re atoms in 2H MoS2 , 2H Mox Re(1- x ) S2 has a high response rejection ratio in the solar-blind ultraviolet (SBUV) region and exhibits a positive photoconductive (PPC) effect. While the 1T' Mox Re(1- x ) S2 formed by heavily doping Mo atoms into 1T' ReS2 will produce a negative photoconductivity (NPC) effect under UV laser irradiation. The optoelectronic property of 2H-1T' Mox Re(1- x ) S2 -based heterostructures can be modulated by gate voltage. These findings are expected to expand the functionality of traditional optoelectronic devices and have potential applications in optoelectronic logic devices.

Marriage of radiotracers and total-body PET/CT rapid imaging system: current status and clinical advances.

Radiotracers and medical imaging equipment are the two main keys to molecular imaging. While radiotracers are of great interest to research and industry, medical imaging equipment technology is blossoming everywhere. Total-body PET/CT (TB-PET/CT) has emerged in response to this trend and is rapidly gaining traction in the fields of clinical oncology, cardiovascular medicine, inflammatory/infectious diseases, and pediatric diseases. In addition, the use of a growing number of radiopharmaceuticals in TB-PET/CT systems has shown promising results. Notably, the distinctive features of TB-PET/CT, such as its ultra-long axial field of view (194 cm), ultra-high sensitivity, and capability for low-dose tracer imaging, have enabled enhanced imaging quality while reducing the radiation dose. The envisioned whole-body dynamic imaging, delayed imaging, personalized disease management, and ultrafast acquisition for motion correction, among others, are achieved. This review highlights two key factors affecting molecular imaging, describing the rapid imaging effects of radiotracers allowed at low doses on TB-PET/CT and the improvements offered compared to conventional PET/CT.

STING is a cell-intrinsic metabolic checkpoint restricting aerobic glycolysis by targeting HK2.

Evasion of antitumour immunity is a hallmark of cancer. STING, a putative innate immune signalling adaptor, has a pivotal role in mounting antitumour immunity by coordinating innate sensing and adaptive immune surveillance in myeloid cells. STING is markedly silenced in various human malignancies and acts as a cell-intrinsic tumour suppressor. How STING exerts intrinsic antitumour activity remains unclear. Here, we report that STING restricts aerobic glycolysis independent of its innate immune function. Mechanistically, STING targets hexokinase II (HK2) to block its hexokinase activity. As such, STING inhibits HK2 to restrict tumour aerobic glycolysis and promote antitumour immunity in vivo. In human colorectal carcinoma samples, lactate, which can be used as a surrogate for aerobic glycolysis, is negatively correlated with STING expression level and antitumour immunity. Taken together, this study reveals that STING functions as a cell-intrinsic metabolic checkpoint that restricts aerobic glycolysis to promote antitumour immunity. These findings have important implications for the development of STING-based therapeutic modalities to improve antitumour immunotherapy.