Membrane Fusion-Mediated Loading of Therapeutic siRNA into Exosome for Tissue-Specific Application.

Tissue-specific delivery of oligonucleotide therapeutics beyond the liver remains a key challenge in nucleic acid drug development. To address this issue, exploiting exosomes as a novel carrier has emerged as a promising approach for efficient nucleic acid drug delivery. However, current exosome-based delivery systems still face multiple hurdles in their clinical applications. Herein, this work presents a strategy for constructing a hybrid exosome vehicle (HEV) through a DNA zipper-mediated membrane fusion approach for tissue-specific siRNA delivery. As a proof-of-concept, this work successfully fuses a liposome encapsulating anti-NFKBIZ siRNAs with corneal epithelium cell (CEC)-derived exosomes to form a HEV construct for the treatment of dry eye disease (DED). With homing characteristics inherited from exosomes, the siRNA-bearing HEV can target its parent cells and efficiently deliver the siRNA payloads to the cornea. Subsequently, the NFKBIZ gene silencing significantly reduces pro-inflammatory cytokine secretions from the ocular surface, reshapes its inflammatory microenvironment, and ultimately achieves an excellent therapeutic outcome in a DED mouse model. As a versatile platform, this hybrid exosome with targeting capability and designed therapeutic siRNAs may hold great potential in various disease treatments.

Pseudomonas aeruginosa outer membrane vesicle-packed sRNAs can enter host cells and regulate innate immune responses.

Bacterial outer membrane vesicles (OMVs) can package and deliver virulence factors into host cells, which is an important mechanism mediating host-pathogen interactions. It has been reported that small RNAs (sRNAs) can be packed into OMVs with varying relative abundance, which might affect the function and/or stability of host mRNAs. In this study, we used OptiPrep density gradient ultra-high-speed centrifugation to purify OMVs from Pseudomonas aeruginosa. Next, the sequences and abundance of sRNAs were detected by using Small RNA-Seq. In particular, sRNA4518698, sRNA2316613 and sRNA809738 were the three most abundant sRNAs in OMVs, which are all fragments of P. aeruginosa non-coding RNAs. sRNAs were shielded within the interior of OMVs and remained resistant to external RNase cleavage. The miRanda and RNAhybrid analysis demonstrated that those sRNAs could target a large number of host mRNAs, which were enriched in host immune responses by the functions of GO and KEGG enrichment. Experimentally, we demonstrated that the transfection of synthetic sRNA4518698, sRNA2316613, or sRNA809738 could reduce the expression of innate immune response genes in RAW264.7 cells. Together, we demonstrated that P. aeruginosa OMVs sRNAs can regulate innate immune responses. This study uncovered a mechanism in which the OMVs regulate host responses by transferring bacterial sRNAs.

Excessive linoleic acid induces muscle oxidative stress through 5-lipoxygenase-dependent peroxidation.

Oxidative stress in muscles is closely related to the occurrence of insulin resistance, muscle weakness and atrophy, age-related sarcopenia, and cancer. Aldehydes, a primary oxidation intermediate of polyunsaturated fatty acids, have been proven to be an important trigger for oxidative stress. However, the potential role of linoleic acid (LA) as a donor for volatile aldehydes to trigger oxidative stress has not been reported. Here, we reported that excessive dietary LA caused muscle redox imbalance and volatile aldehydes containing hexanal, 2-hexenal, and nonanal were the main metabolites leading to oxidative stress. Importantly, we identified 5-lipoxygenase (5-LOX) as a key enzyme mediating LA peroxidation in crustaceans for the first time. The inhibition of 5-LOX significantly suppressed the content of aldehydes produced by excessive LA. Mechanistically, the activation of the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway facilitated the translocation of 5-LOX from the nucleus to the cytoplasm, where 5-LOX oxidized LA, leading to oxidative stress through the generation of aldehydes. This study suggests that 5-LOX is a potential target to prevent the production of harmful aldehydes.

A Nucleic Acid-Based LYTAC Plus Platform to Simultaneously Mediate Disease-Driven Protein Downregulation.

Protein degradation techniques, such as proteolysis-targeting chimeras (PROTACs) and lysosome-targeting chimeras (LYTACs), have emerged as promising therapeutic strategies for the treatment of diseases. However, the efficacy of current protein degradation methods still needs to be improved to address the complex mechanisms underlying diseases. Herein, a LYTAC Plus hydrogel engineered is proposed by nucleic acid self-assembly, which integrates a gene silencing motif into a LYTAC construct to enhance its therapeutic potential. As a proof-of-concept study, vascular endothelial growth factor receptor (VEGFR)-binding peptides and mannose-6 phosphate (M6P) moieties into a self-assembled nucleic acid hydrogel are introduced, enabling its LYTAC capability. Small interference RNAs (siRNAs) is then employed that target the angiopoietin-2 (ANG-2) gene as cross-linkers for hydrogel formation, giving the final LYTAC Plus hydrogel gene silencing ability. With dual functionalities, the LYTAC Plus hydrogel demonstrated effectiveness in simultaneously reducing the levels of VEGFR-2 and ANG-2 both in vitro and in vivo, as well as in improving therapeutic outcomes in treating neovascular age-related macular degeneration in a mouse model. As a general material platform, the LYTAC Plus hydrogel may possess great potential for the treatment of various diseases and warrant further investigation.

Effects of a high-fat and high-carbohydrate diet on appetite regulation and central AMPK in the hypothalamus of blunt snout bream (Megalobrama amblycephala).

Adenosine monophosphate-activated protein kinase (AMPK) is a sensor of cellular energy changes and controls food intake. This study investigates the effect of a high-calorie diet (high fat diet [HFD], high carbohydrate diet [HCD] and high energy diet [HED]) on appetite and central AMPK in blunt snout bream. In the present study, fish (average initial weight 45.84 ± 0.07 g) were fed the control, HFD, HCD and HED in four replicates for 12 weeks. At the end of the feeding trial, the result showed that body mass index, specific growth rate, feed efficiency ratio and feed intake were not affected (p > 0.05) by dietary treatment. However, fish fed the HFD obtained a significantly higher (p < 0.05) lipid productive value, lipid gain and lipid intake than those fed the control diet, but no significant difference was attributed to others. Also, a significantly higher (p < 0.05) energy intake content was found in fish-fed HFD, HCD and HED than those given the control diet. Long-term HFD and HCD feeding significantly increased (p < 0.05) plasma glucose, glycated serum protein, advanced glycation end product, insulin and leptin content levels than the control group. Moreover, a significantly lower (p < 0.05) complex 1, 2 and 3 content was found in fish-fed HFD and HCD than in the control, but no differences (p > 0.05) were attributed to those in HED. Fish-fed HED significantly upregulated (p < 0.05) hypothalamic ampα 1 and ampα 2 expression, whereas the opposite trend was observed in the hypothalamic mammalian target of rapamycin than those in HFD and HCD compared to the control. However, hypothalamic neuropeptide y, peroxisome proliferator-activated receptor α (pparα), acetyl-coa oxidase and carnitine palmitoyltransferase 1 were significantly upregulated (p < 0.05) in the HCD group, while the opposite was seen in cholecystokinin expression compared to those in the control group. Our findings indicated that the central AMPK signal pathway and appetite were modulated according to the diet's energy level to regulate nutritional status and maintain energy homoeostasis in fish.

In Situ Vaccination with An Injectable Nucleic Acid Hydrogel for Synergistic Cancer Immunotherapy.

Recently, therapeutic cancer vaccines have emerged as promising candidates for cancer immunotherapy. Nevertheless, their efficacies are frequently impeded by challenges including inadequate antigen encapsulation, insufficient immune activation, and immunosuppressive tumor microenvironment. Herein, we report a three-in-one hydrogel assembled by nucleic acids (NAs) that can serve as a vaccine to in situ trigger strong immune response against cancer. Through site-specifically grafting the chemodrug, 7-ethyl-10-hydroxycamptothecin (also known as SN38), onto three component phosphorothioate (PS) DNA strands, a Y-shaped motif (Y-motif) with sticky ends is self-assembled, at one terminus of which an unmethylated cytosine-phosphate-guanine (CpG) segment is introduced as an immune agonist. Thereafter, programmed cell death ligand-1 (PD-L1) siRNA that performs as immune checkpoint inhibitor is designed as a crosslinker to assemble with the CpG- and SN38-containing Y-motif, resulting in the formation of final NA hydrogel vaccine. With three functional agents inside, the hydrogel can remarkably induce the immunogenic cell death to enhance the antigen presentation, promoting the dendritic cell maturation and effector T lymphocyte infiltration, as well as relieving the immunosuppressive tumor environment. When inoculated twice at tumor sites, the vaccine demonstrates a substantial antitumor effect in melanoma mouse model, proving its potential as a general platform for synergistic cancer immunotherapy.

Folic acid blocks ferroptosis induced by cerebral ischemia and reperfusion through regulating folate hydrolase transcriptional adaptive program.

Cerebral ischemia-reperfusion (I/R) injury is notably linked with folic acid (FA) deficiency. The aim of our investigation was to explore the effects and underlying mechanisms by which FA mitigates I/R, specifically through regulating the GCPII transcriptional adaptive program. Initially, we discovered that following cerebral I/R, levels of FA, methionine synthase (MTR), and methylenetetrahydrofolate reductase (MTHFR) were decreased, while GCPII expression was elevated. Secondly, administering FA could mitigate cognitive impairment and neuronal damage induced by I/R. Thirdly, the mechanism of FA supplementation involved suppressing the transcriptional factor Sp1, subsequently inhibiting GCPII transcription, reducing Glu content, obstructing cellular ferroptosis, and alleviating cerebral I/R injury. In summary, our data demonstrate that FA affords protection against cerebral I/R injury by inhibiting the GCPII transcriptional adaptive response. These findings unveil that targeting GCPII might be a viable therapeutic strategy for cerebral I/R.

Impact of ovary-sparing treatment planning on plan quality, treatment time and gamma passing rates in intensity-modulated radiotherapy for stage I/II cervical cancer.

BACKGROUND: This study aimed to investigate the impact of ovary-sparing intensity-modulated radiotherapy (IMRT) on plan quality, treatment time, and gamma passing rates for stage I/II cervical cancer patients. METHODS: Fifteen stage I/II cervical cancer patients were retrospectively enrolled, and a pair of clinically suitable IMRT plans were designed for each patient, with (Group A) and without (Group B) ovary-sparing. Plan factors affecting plan quality, treatment time, and gamma passing rates, including the number of segments, monitor units, percentage of small-area segments (field area < 20 cm2), and percentage of small-MU segments (MU < 10), were compared and statistically analyzed. Key plan quality indicators, including ovarian dose, target dose coverage (D98%, D95%, D50%, D2%), conformity index, and homogeneity index, were evaluated and statistically assessed. Treatment time and gamma passing rates collected by IBA MatriXX were also compared. RESULTS: The median ovarian dose in Group A and Group B was 7.61 Gy (range 6.71-8.51 Gy) and 38.52 Gy (range 29.84-43.82 Gy), respectively. Except for monitor units, all other plan factors were significantly lower in Group A than in Group B (all P < .05). Correlation coefficients between plan factors, treatment time, and gamma passing rates that were statistically different were all negative. Both Groups of plans met the prescription requirement (D95% ≥ 45.00 Gy) for clinical treatment. D98% was smaller for Group A than for Group B (P < .05); D50% and D2% were larger for Group A than for Group B (P < .05, P < .05). Group A plans had worse conformity index and homogeneity index than Group B plans (P < .05, P < .05). Treatment time did not differ significantly (P > .05). Gamma passing rates in Group A were higher than in Group B with the criteria of 2%/3 mm (P < .05) and 3%/2 mm (P < .05). CONCLUSION: Despite the slightly decreased quality of the treatment plans, the ovary-sparing IMRT plans exhibited several advantages including lower ovarian dose and plan complexity, improved gamma passing rates, and a negligible impact on treatment time.

Hepatocellular Carcinoma Subtyping and Prognostic Model Construction Based on Chemokine-Related Genes.

BACKGROUND: Chemokines not only regulate immune cells but also play significant roles in development and treatment of tumors and patient prognoses. However, these effects have not been fully explained in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: We conducted a clustering analysis of chemokine-related genes. We then examined the differences in survival rates and analyzed immune levels using single-sample Gene Set Enrichment Analysis (ssGSEA) for each subtype. Based on chemokine-related genes of different subtypes, we built a prognostic model in The Cancer Genome Atlas (TCGA) dataset using the survival package and glmnet package and validated it in the Gene Expression Omnibus (GEO) dataset. We used univariate and multivariate regression analyses to select independent prognostic factors and used R package rms to draw a nomogram reflecting patient survival rates at 1, 3, and 5 years. RESULTS: We identified two chemokine subtypes and, after screening, found that Cluster1 had higher survival rates than Cluster2. In addition, in terms of immune evaluation, stromal evaluation, ESTIMATE evaluation, immune abundance, immune function, and expressions of various immune checkpoints, immune levels of Cluster1 were significantly better than those of Cluster2. The immunophenoscore (IPS) of HCC patients in Cluster1 was significantly higher than that in Cluster2. Furthermore, we established a prognostic model consisting of 9 genes, which correlated with chemokines. Through testing, Riskscore was revealed as an independent prognostic factor, and the model could effectively predict HCC patients' prognoses in both TCGA and GEO datasets. CONCLUSION: This study resulted in the development of a novel prognostic model related to chemokine genes, providing new targets and theoretical support for HCC patients.

Dosimetric performance evaluation of the Halcyon treatment platform for stereotactic radiotherapy: A pooled study.

With the advancement of radiotherapy equipment, stereotactic radiotherapy (SRT) has been increasingly used. Among the many radiotherapy devices, Halcyon shows promising applications. This article reviews the dosimetric performance such as plan quality, plan complexity, and gamma passing rates of SRT plans with Halcyon to determine the effectiveness and safety of Halcyon SRT plans. This article retrieved the last 5 years of PubMed studies on the effectiveness and safety of the Halcyon SRT plans. Two authors independently reviewed the titles and abstracts to decide whether to include the studies. A search was conducted to identify publications relevant to evaluating the dosimetric performance of SRT plans on Halcyon using the key strings Halcyon, stereotactic radiosurgery, SRT, stereotactic body radiotherapy, and stereotactic ablative radiotherapy. A total of 18 eligible publications were retrieved. Compared to SRT plans on the TrueBeam, the Halcyon has advantages in terms of plan quality, plan complexity, and gamma passing rates. The high treatment speed of SRT plans on the Halcyon is impressive, while the results of its plan evaluation are also encouraging. As a result, Halcyon offers a new option for busy radiotherapy units while significantly improving patient comfort in treatment. For more accurate results, additional relevant publications will need to be followed up in subsequent studies.

Effects of overtreatment with different attachment positions on maxillary anchorage enhancement with clear aligners: a finite element analysis study.

BACKGROUND: The effect of attachment positions on anchorage has not been fully explored. The aim of the present study is to analyze the effect of overtreatment with different anchorage positions on maxillary anchorage enhancement with clear aligners in extraction cases. METHODS: Models of the maxilla and maxillary dentition were constructed and imported into SOLIDWORKS software to create periodontal ligament (PDL), clear aligners, and attachments. Attachment positions on second premolars included: without attachment (WOA), buccal attachment (BA), and bucco-palatal attachment (BPA). Overtreatment degrees were divided into five groups (0°, 1°, 2°, 3°, 4°) and added on the second premolars. The calculation and analysis of the displacement trends and stress were performed using ANSYS software. RESULTS: Distal tipping and extrusion of the canines, and mesial tipping and intrusion of the posterior teeth occurred during retraction. A strong anchorage was achieved in cases of overtreatment of 2.8° with BA and 2.4° with BPA. Moreover, the BPA showed the best in achieving bodily control of the second premolars. When the overtreatment was performed, the canines and first molars also showed reduced tipping trends with second premolars attachments. And the stress on the PDL and the alveolar bone was significantly relieved and more evenly distributed in the BPA group. CONCLUSIONS: Overtreatment is an effective means for anchorage enhancement. However, the biomechanical effect of overtreatment differs across attachment positions. The BPA design performs at its best for stronger overtreatment effects with fewer adverse effects.

Oral bovine serum albumin administration alleviates inflammatory signals and improves antioxidant capacity and immune response under thioacetamide stress in blunt snout bream fed a high-calorie diet.

This investigation looks at the impact of oral bovine serum albumin (BSA) on antioxidants, immune responses, and inflammation signals in blunt snout bream fed a high-calorie diet. 480 fish (average weight: 45.84 ± 0.07 g) were randomly fed a control diet, a high-fat diet (HFD), a high carbohydrate diet (HCD), and a high-energy diet (HED) in six replicates for 12 weeks. After the feeding trial, fish were orally administered with 10% BSA for 10 h, then blood and liver samples from five fish were randomly obtained after 10 h to determine plasma inflammatory markers and inorganic components. Also, the leftover fish were injected with thioacetamide, blood and liver samples were simultaneously obtained at 12, 48, and 96 h, respectively, to determine antioxidant, immune, and inflammatory signals, with survival rates recorded at the same time interval. After 10 h, plasma inflammatory markers such as tumour necrosis factors (TNF-α), interleukin 6 (IL6), nitric oxide (NO), Monocyte chemoattractant protein-1(MCP-1), and cortisol were significantly improved in fish fed HCD and HED as compared to the control. After thioacetamide stress, plasma lysozyme (LYM), complement 3, myeloperoxidase (MPO), and alkaline phosphatase activities, as well as immunoglobulin M, levels all increased significantly (P < 0.05) with increasing time with maximum value attained at 96 h, but shows no difference among dietary treatment. Similar results were observed in liver superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities and malondialdehyde (MDA) content, but tended to reduce at 96 h. nf-kb, tnf-α, and mcp-1 tend to decrease with the minimum value attained at 48 h and gradually decrease with increasing time at 96 h. After 96 h of the thioacetamide (TAA) challenge, the survival rate of blunt snout bream fed with an HFD and HCD was significantly lower (P < 0.05) at 48, and 96 h before the administration of BSA. However, no differences were observed among dietary treatments after the BSA administration. Overall, this study indicated that oral dietary administration of BSA might greatly enhance the antioxidant capability and innate immunity and mitigates inflammation signals after TAA stress in blunt snout bream fed high energy diet.

COVID-19 vaccination coverage and its cognitive determinants among older adults in Shanghai, China, during the COVID-19 epidemic.

Objectives: This study aimed to examine the coverage of coronavirus disease 2019 (COVID-19) vaccination and its cognitive determinants among older adults. Methods: A cross-sectional study was conducted using a questionnaire to conduct a survey among 725 Chinese older adults aged 60 years and above in June 2022, 2 months after the mass COVID-19 outbreak in Shanghai, China. The questionnaire covered demographic characteristics, COVID-19 vaccination status, internal risk perception, knowledge, and attitude toward the efficacy and safety of COVID-19 vaccines. Results: The vaccination rate was 78.3% among the surveyed individuals. Self-reported reasons for unwillingness to get vaccinated (multiple selections) were "concerns about acute exacerbation of chronic diseases after vaccination (57.3%)" and "concerns regarding vaccine side effects (41.4%)." Compared to the unvaccinated group, the vaccinated group tended to have a higher score in internal risk perception (t = 2.64, P < 0.05), better knowledge of COVID-19 vaccines (t = 5.84, P < 0.05), and a more positive attitude toward the efficacy and safety of COVID-19 vaccines (t = 7.92, P < 0.05). The path analysis showed that the cognitive effect on vaccination behavior is relatively large, followed by the internal risk perception, and then the attitude toward COVID-19 vaccines. The more knowledgeable the participants were about COVID-19 vaccines, the more likely they were to receive the COVID-19 vaccines. In the multivariate logistic regression, the increased coverage of COVID-19 vaccination was associated with reduced age (OR = 0.53 95% CI 0.43-0.66, P < 0.001), being a resident in other places than Shanghai (OR = 0.40, 95% CI 0.17-0.92, P < 0.05), a shorter time of lockdown (OR = 0.33, 95% CI 0.13-0.83, P < 0.05), a history of other vaccines (OR = 2.58, 95% CI 1.45-4.60, P < 0.01), a fewer number of chronic diseases (OR = 0.49, 95% CI 0.38-0.62, P < 0.001), better knowledge about COVID-19 vaccines (OR = 1.60, 95% CI 1.17-2.19, P < 0.01), and a positive attitude toward COVID-19 vaccines (OR = 9.22, 95% CI 4.69-18.09, P < 0.001). Conclusion: Acquiring accurate knowledge and developing a positive attitude toward COVID-19 vaccines are important factors associated with COVID-19 vaccination. Disseminating informed information on COVID-19 vaccines and ensuring efficacious communication regarding their efficacy and safety would enhance awareness about COVID-19 vaccination among older adults and consequently boost their vaccination coverage.

Rational Design of Mesoporous Coordination Polymer Nanophotosensitizers for Photodynamic Tumor Ablation.

Effective clinical practice of precise photodynamic therapy (PDT) is severely impeded by the inherent drawbacks and aggregation propensity of conventional photosensitizers. An all-in-one approach is highly desired to optimize structural features, photophysical properties, and pharmacokinetic behaviors of photosensitizers. Herein, we have fabricated mesoporous boron dipyrromethene-bridged coordination polymer nanophotosensitizers (BCP-NPs) for high-performance PDT via a unique solvent-assisted assembly strategy. Distinctive photophysical and structural characteristics of BCP-NPs confer enhanced photodynamic activities, together with high cellular uptake and ultrahigh stability. Moreover, BCP-NPs showed excellent tumor accumulation and prolonged tumor retention, achieving eradication of the triple-negative breast cancer (TNBC) model under low-power-density LED irradiation. This work has provided a valuable paradigm for the construction of mesoporous photoactive nanomaterials for biophotonic applications.

The coupling system of magnetite-enhanced thermophilic hydrolysis-acidification and denitrification for refractory organics removal from anaerobic digestate food waste effluent (ADFE).

The aim of this study was to remove the refractory organics from high-temperature anaerobic digestate food waste effluent by the coupling system of hydrolysis-acidification and denitrification. Iron-based materials (magnetite, zero-valent iron, and iron-carbon) were used to enhance the performance of thermophilic hydrolysis-acidification. Compared with the control group, magnetite had the best strengthening effect, increasing volatile fatty acids concentration and fluorescence intensity of easily biodegradable organics in the effluent by 47.6 % and 108.4 %, respectively. The coupling system of magnetite-enhanced thermophilic hydrolysis-acidification and denitrification achieved a nitrate removal efficiency of 91.2 % (influent NO3--N was 150 mg L-1), and reduced the fluorescence intensity of refractory organics by 33.8 %, compared with influent. Microbiological analysis indicated that magnetite increased the relative abundance of thermophilic hydrolytic acidifying bacteria, and coupling system enriched some genera simultaneously removing nitrate and refractory organics. This study provided fresh information on refractory organics and nitrogen removal of thermophilic wastewater biologically.

Interactive effects of dietary leucine and isoleucine affect amino acid profile and metabolism through AKT/TOR signaling pathways in blunt snout bream (Megalobrama amblycephala).

The purpose of this research is to explore the interaction between dietary leucine and isoleucine levels on whole-body composition, plasma and liver biochemical indexes, amino acids deposition in the liver, and amino acid metabolism of blunt snout bream (Megalobrama amblycephala). The test fish (average weight: 56.00 ± 0.55 g) were fed one of six diets at random containing two leucine levels (1.70% and 2.50%) and three isoleucine levels (1.00%, 1.20%, and 1.40%) for 8 weeks. The results showed that the final weight and weight gain rate were the highest in the fish fed low-level leucine and high-level isoleucine diets (P > 0.05). Furthermore, the crude lipid content was significantly adjusted by diets with diverse levels of leucine and isoleucine (P < 0.05). In addition, interactive effects of these two branched-chain amino acids (BCAAs) were found on plasma total protein, blood ammonia, and blood urea nitrogen of test fish (P < 0.05). Additionally, the liver amino acid profiles were significantly influenced by the interactive effects of the two BCAAs (P < 0.05). Moreover, interactive effects of dietary leucine and isoleucine were significantly observed in the expressions of amino acid metabolism-related genes (P < 0.05). These findings suggested that dietary leucine and isoleucine had interaction. Meanwhile, the interaction between them was more conducive to the growth and quality improvement of blunt snout bream when the dietary leucine level was 1.70% and isoleucine level was 1.40%.

Planning issues on linac-based stereotactic radiotherapy.

This work aims to summarize and evaluate the current planning progress based on the linear accelerator in stereotactic radiotherapy (SRT). The specific techniques include 3-dimensional conformal radiotherapy, dynamic conformal arc therapy, intensity-modulated radiotherapy, and volumetric-modulated arc therapy (VMAT). They are all designed to deliver higher doses to the target volume while reducing damage to normal tissues; among them, VMAT shows better prospects for application. This paper reviews and summarizes several issues on the planning of SRT to provide a reference for clinical application.

Graph neural network for integrated water network partitioning and dynamic district metered areas.

Water distribution systems (WDSs) are used to transmit and distribute water resources in cities. Water distribution networks (WDNs) are partitioned into district metered areas (DMAs) by water network partitioning (WNP), which can be used for leak control, pollution monitoring, and pressure optimization in WDS management. In order to overcome the limitations of optimal search range and the decrease of recovery ability caused by two-step WNP and fixed DMAs in previous studies, this study developed a new method combining a graph neural network to realize integrated WNP and dynamic DMAs to optimize WDS management and respond to emergencies. The proposed method was tested in a practical case study; the results showed that good hydraulic performance of the WDN was maintained and that dynamic DMAs demonstrated excellent stability in emergency situations, which proves the effectiveness of the method in WNP.

Clinical applications of concentrated growth factors membrane for sealing the socket in alveolar ridge preservation: a randomized controlled trial.

The purpose of this study was to evaluate the efficacy of concentrated growth factor (CGF) membrane for the sealing of alveolar socket in alveolar ridge preservation (ARP). A total of 22 patients with 24 alveolar sockets were recruited and divided randomly into CGF group and Bio-Gide collagen membrane group. The soft tissue wound healing rate was calculated using intraoral scanner at 3, 7, and 14 days after ARP, and the bone resorption volume at 1, 3, and 5 mm below the alveolar ridge was measured by CBCT at 6 months postoperation. The keratinized gingival width was also measured before and 6 months after ridge preservation. In terms of soft tissue healing rate, the CGF group exhibited significant higher than that of Bio-Gide group at both 7 and 14 days after surgery (P < 0.05). However, there was no significantly different in bone resorption rate and the width of keratinized gingival after 6 months (P > 0.05). Therefore, the use of CGFs membranes for wound closure in ARP is a reliable method, but more clinical data are needed to prove it.

Perioperative management of intrahepatic cholangiocarcinoma patients with hereditary coagulation factor V deficiency: a case report and literature review.

Background: Coagulation factor V (FV) is an essential factor to regulate and participate in the initial coagulation reaction, and it is the most important prothrombin activator in vivo. FV congenital deficiency is a rare hereditary disease, it exposes patients to hemorrhagic risk, with high morbi-mortality. Clinically, laparoscopic major hepatectomy has its own risk of intraoperative hemorrhage, and moreover, coupled with the lack of FV will increase the risk of bleeding even life-threatening. However, several studies have reported the cases of patients with FV deficiency undergoing surgery, there is no report of laparoscopic major hepatectomy in patients with FV deficiency so far. Case Description: Here, we reported one case with no abdominal pain, nausea, vomiting, fever and other discomfort who was diagnosed with intrahepatic cholangiocarcinoma (IHC) complicated with hereditary FV deficiency and then received laparoscopic left hemihepatectomy after conversion therapy. After preoperative sufficient infusion of fresh frozen plasma (FFP) to improve coagulation function, careful intraoperative operation, and strict postoperative monitoring, no obvious complications occurred in the perioperative period. At present, the patient has an overall survival time of 18 months and is still followed up. Conclusions: It is suggested that laparoscopic major hepatectomy is safe and feasible for patients with hereditary FV deficiency under careful perioperative management.