The photosynthetic performance and photoprotective role of carotenoids response to light stress in intertidal red algae Neoporphyra haitanensis.

Neoporphyra haitanensis, a red alga harvested for food, thrives in the intertidal zone amid dynamic and harsh environments. High irradiance represents a major stressor in this habitat, posing a threat to the alga's photosynthetic apparatus. Interestingly, N. haitanensis has adapted to excessive light despite the absence of a crucial xanthophyll cycle-dependent photoprotection pathway. Thus, it is valuable to investigate the mechanisms by which N. haitanensis copes with excessive light and to understand the photoprotective roles of carotenoids. Under high light intensities and prolonged irradiation time, N. haitanensis displayed reduction in photosynthetic efficiency and phycobiliproteins levels, as well as different responses in carotenoids. The decreased carotene contents suggested their involvement in the synthesis of xanthophylls, as evidenced by the up-regulation of lycopene-ß-cyclase (lcyb) and zeaxanthin epoxidase (zep) genes. Downstream xanthophylls such as lutein, zeaxanthin, and antheraxanthin increased proportionally to light stress, potentially participating in scavenging reactive oxygen species (ROS). When accompanied by the enhanced activity of ascorbate peroxidase (APX), these factors resulted in a reduction in ROS production. The responses of intermediates α-cryptoxanthin and ß-cryptoxanthin were felt somewhere between carotenes and zeaxanthin/lutein. Furthermore, these changes were ameliorated when the organism was placed in darkness. In summary, down-regulation of the organism's photosynthetic capacity, coupled with heightened xanthophylls and APX activity, activates photoinhibition quenching (qI) and antioxidant activity, helping N. haitanensis to protect the organism from the damaging effects of excessive light exposure. These findings provide insights into how red algae adapt to intertidal lifestyles.

A new Urbacodon (Theropoda, Troodontidae) from the Upper Cretaceous Iren Dabasu Formation, China: Implications for troodontid phylogeny and tooth biology.

Tooth attachment and replacement play significant roles in the feeding ecology of polyphyodont vertebrates, yet these aspects have remained largely unexplored in non-avialan paravians including troodontids. Here, we describe a new troodontid species, Urbacodon norelli sp.n., recovered from the Upper Cretaceous Iren Dabasu Formation of Inner Mongolia, China, based on an incomplete right dentary and 12 associated replacement teeth. Urbacodon norelli is distinguished from all other known troodontids, including its relative U. itemirensis from Uzbekistan, by several features: the presence of paired dentary symphyseal foramina, the presence of a relatively steep anterior margin of the dentary, the absence of a dentary chin, the presence of a common groove hosting the anterior 12 dentary teeth, and the presence of relatively larger dentary teeth. Phylogenetic analysis places both species of Urbacodon as sister taxa to Zanabazar junior, confirming their status as later-diverging troodontids. Radiographs revealed an alternating tooth replacement pattern in U. norelli, with a maximum Zahnreihen-spacing estimated to be 3. During tooth replacement, the anteriorly inclined interdental septa, which wedge between anterior dentary teeth, underwent frequent remodelling as the developing tooth moved upwards, particularly anterolabially. This rapid turnover left insufficient time for an interdental plate to form, resulting in the absence of such structures in this specimen. The frequent remodelling of periodontal tissues accompanying tooth replacement is likely to account for the absence of interdental plates. The discovery of this new troodontid expands our understanding of paravian theropods from the Upper Cretaceous Iren Dabasu Formation and provides valuable insights into troodontid tooth biology.

Dynamics modeling and nonlinear attitude controller design for a rocket-type unmanned aerial vehicle.

This paper presents an altitude and attitude control system for a newly designed rocket-type unmanned aerial vehicle (UAV) propelled by a gimbal-based coaxial rotor system (GCRS) enabling thrust vector control (TVC). The GCRS is the only means of actuation available to control the UAV's orientation, and the flight dynamics identify the primary control difficulty as the highly nonlinear and tightly coupled control distribution problem. To address this, the study presents detailed derivations of attitude flight dynamics and a control strategy to track the desired attitude trajectory. First, a Proportional-Integral-Derivative (PID) control algorithm is developed based on the formulation of linear matrix inequality (LMI) to ensure robust stability and performance. Second, an optimization algorithm using the Levenberg-Marquardt (LM) method is introduced to solve the nonlinear inverse mapping problem between the control law and the actual actuator outputs, addressing the nonlinear coupled control input distribution problem of the GCRS. In summary, the main contribution is the proposal of a new TVC UAV system based on GCRS. The PID control algorithm and LM algorithm were designed to solve the distribution problem of the actuation model and confirm altitude and attitude tracking missions. Finally, to validate the flight properties of the rocket-type UAV and the performance of the proposed control algorithm, several numerical simulations were conducted. The results indicate that the tightly coupled control input nonlinear inverse problem was successfully solved, and the proposed control algorithm achieved effective attitude stabilization even in the presence of disturbances.

Phase I clinical trial of intracerebral injection of lentiviral-ABCD1 for the treatment of cerebral adrenoleukodystrophy.

This was a single-arm, multicenter, open-label phase I trial. Lentiviral vectors (LV) carrying the ABCD1 gene (LV-ABCD1) was directly injected into the brain of patients with childhood cerebral adrenoleukodystrophy (CCALD), and multi-site injection was performed. The injection dose increased from 200 to 1600 µL (vector titer: 1×109 TU/mL), and the average dose per kilogram body weight ranges from 8 to 63.6 µL/kg. The primary endpoint was safety, dose-exploration and immunogenicity and the secondary endpoint was initial evaluation of efficacy and the expression of ABCD1 protein. A total of 7 patients participated in this phase I study and were followed for 1 year. No injection-related serious adverse event or death occurred. Common adverse events associated with the injection were irritability (71%, 5/7) and fever (37.2 â„ƒ-38.5 â„ƒ, 57%, 4/7). Adverse events were mild and self-limited, or resolved within 3 d of symptomatic treatment. The maximal tolerable dose is 1600 µL. In 5 cases (83.3%, 5/6), no lentivirus associated antibodies were detected. The overall survival at 1-year was 100%. The ABCD1 protein expression was detected in neutrophils, monocytes and lymphocytes. This study suggests that the intracerebral injection of LV-ABCD1 for CCALD is safe and can achieve successful LV transduction in vivo; even the maximal dose did not increase the risk of adverse events. Furthermore, the direct LV-ABCD1 injection displayed low immunogenicity. In addition, the effectiveness of intracerebral LV-ABCD1 injection has been preliminarily demonstrated while further investigation is needed. This study has been registered in the Chinese Clinical Trial Registry (https://www.chictr.org.cn/, registration number: ChiCTR1900026649).

Effects of active vitamin D analogs and calcimimetic agents on PTH and bone mineral biomarkers in hemodialysis patients with SHPT: a network meta-analysis.

OBJECTIVE: Active vitamin D analogs and calcimimetic agents are primary drugs for patients with secondary hyperparathyroidism. Due to the different pharmacological mechanisms, they have different effects on the level of parathyroid hormone, serum calcium, phosphorus, and bone turnover biomarkers. This study aimed to evaluate the active vitamin D analogs and calcimimetic agents in hemodialysis patients with secondary hyperparathyroidism. METHODS: We included randomized clinical trials of hemodialysis patients with secondary hyperparathyroidism, comparing active vitamin D analogs to calcimimetic agents or placebo/control. The primary outcome was the change of PTH level from baseline to end-up. The secondary outcome was the change in serum calcium, phosphorus, calcium-phosphorus product, and bone turnover biomarkers. A network meta-analysis method was applied to complete this study. The forest plots reflected statistical differences in the outcomes between active vitamin D analogs and calcimimetic agents. The SUCRA result presented the ranking of impact on the outcomes. RESULTS: Twenty-one randomized clinical trials with 4653 patients were included in this network meta-analysis. Global and splitting-node inconsistencies provided no evidence of inconsistency in this study. There was no statistical difference between two active vitamin D analogs and three calcimimetic agents in the PTH, and phosphorus levels changed. Considering serum calcium level, compared with placebo, calcitriol (9.73, 3.09 to 16.38) and paricalcitol (9.74, 3.87 to 15.60) increase serum calcium. However, cinacalcet (- 1.94, - 3.72 to - 0.15) and etelcalcetide (- 7.80, - 11.80 to - 3.80) reduced the serum calcium, even a joint use of cinacalcet with active vitamin D analogs (- 5.83, - 9.73 to - 1.93). Three calcimimetic agents decreased calcium levels much more than calcitriol and paricalcitol. The same type of drugs was not distinct, with each one affecting the change in calcium level. Cinacalcet reduced calcium-phosphorus product much more than paricalcitol (- 3.66, - 6.72 to - 0.60). Evocalcet decreased calcium-phosphorus product more than cinacalcet (- 5.64, - 8.91 to - 2.37), calcitriol (- 9.36, - 14.81 to - 3.92), and paricalcitol (- 9.30, - 13.78 to - 4.82). Compared with paricalcitol, cinacalcet significantly increases the level of ALP (24.50, 23.05 to 25.95) and bALP (0.67, 0.03 to 1.31). The incidence of gastrointestinal disorders in cinacacet (29.35, 1.71 to 504.98) and etelcalcetide (20.92, 1.20 to 365.68) was notably higher than in paricalcitol. Etelcalcetide (0.71, 0.53 to 0.96) and evocalcet (0.46, 0.33 to 0.64) presented a lower rate of gastrointestinal disorders than cinacalcet. Cinacalcet ranked first in adverse gastrointestinal, nervous, and respiratory reactions. CONCLUSION: The same kinds of agents perform similar efficacy on the level of PTH, serum calcium, phosphorus, and calcium-phosphorus product. Paricalcitol did not lead to more hypercalcemia than calcitriol. The calcium decrease induced by cinacalcet was not settled even by associating it with active vitamin D analogs. Cinacalcet and evocalcet were superior to calcitriol and paricacitol in reducing calcium-phosphorus product. Calcimimetics induced more gastrointestinal disorders than active vitamin D analogs, especially cinacalcet.

MYBL2 is a Novel Independent Prognostic Biomarker and Correlated with TMB in pancreatic cancer.

Background: Pancreatic cancer continues to pose a significant threat due to its high mortality rate. While MYB family genes have been identified as oncogenes in certain cancer types, their role in pancreatic cancer remains largely unexplored. Methods: The mRNA and protein expression of MYB family genes in pancreatic cancer samples was analyzed using TNMplot, HPA, and TISBID online bioinformatics tools, sourced from the TCGA and GETx databases. The relationship between MYB family gene expression and survival time was assessed through Kaplan-Meier analysis, while the prognostic impact of MYB family gene expression was evaluated using the Cox proportional hazards model. Additionally, Spearman's correlation analysis was employed to investigate the correlation between MYB family genes and TMB/MSI. Results: The integration of data from various databases demonstrated that all MYB family genes exhibited dysregulated expression in pancreatic cancer. However, only the expression of the MYBL2 gene displayed a notable association with the grade and stage of pancreatic cancer. Furthermore, the MYBL2 gene exhibited significant variations in both univariate and multivariate factor analyses.Subsequent functional analyses revealed a significant correlation between MYBL2 expression in pancreatic cancers and various biological processes, such as DNA replication, tumor proliferation, G2M checkpoint regulation, pyrimidine metabolism, and the P53 pathway. Additionally, a notable positive association was observed between MYBL2 expression and tumor mutational burden (TMB), a predictive indicator for response to PD1 antibody treatment. Conclusion: MYBL2 may be a double marker for independent diagnosis and PD1 antibody response prediction of pancreatic cancer patients.

A ferritin-based nanoparticle displaying a neutralizing epitope for foot-and-mouth disease virus (FMDV) confers partial protection in guinea pigs.

BACKGROUND: Foot-and-mouth disease (FMD) is a devastating disease affecting cloven-hoofed animals, that leads to significant economic losses in affected countries and regions. Currently, there is an evident inclination towards the utilization of nanoparticles as powerful platforms for innovative vaccine development. Therefore, this study developed a ferritin-based nanoparticle (FNP) vaccine that displays a neutralizing epitope of foot-and-mouth disease virus (FMDV) VP1 (aa 140-158) on the surface of FNP, and evaluated the immunogenicity and protective efficacy of these FNPs in mouse and guinea pig models to provide a strategy for developing potential FMD vaccines. RESULTS: This study expressed the recombinant proteins Hpf, HPF-NE and HPF-T34E via an E. coli expression system. The results showed that the recombinant proteins Hpf, Hpf-NE and Hpf-T34E could be effectively assembled into nanoparticles. Subsequently, we evaluated the immunogenicity of the Hpf, Hpf-NE and Hpf-T34E proteins in mice, as well as the immunogenicity and protectiveness of the Hpf-T34E protein in guinea pigs. The results of the mouse experiment showed that the immune efficacy in the Hpf-T34E group was greater than the Hpf-NE group. The results from guinea pigs immunized with Hpf-T34E showed that the immune efficacy was largely consistent with the immunogenicity of the FMD inactivated vaccine (IV) and could confer partial protection against FMDV challenge in guinea pigs. CONCLUSIONS: The Hpf-T34E nanoparticles stand out as a superior choice for a subunit vaccine candidate against FMD, offering effective protection in FMDV-infected model animals. FNP-based vaccines exhibit excellent safety and immunogenicity, thus representing a promising strategy for the continued development of highly efficient and safe FMD vaccines.

Hybridization of bimetallic cobalt-molybdenum oxide multihole nanosheets with selenium adulteration as advanced bifunctional electrocatalysts for boosting overall water splitting.

Electrocatalytic water splitting produces green and pollution-free hydrogen as a clean energy carrier, which can effectively alleviate energy crisis. In this paper, bimetallic and selenium doped cobalt molybdate (Se-CoMoO4) nanosheets with rough surface are resoundingly prepared. The multihole Se-CoMoO4 nanosheets display ultrathin and rectangular architecture with the dimensions of âˆ¼ 3.5 µm and 700 nm for length and width, respectively. The Se-CoMoO4 electrocatalyst shows remarkable water electrolysis activity and stability. The overpotentials of oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) are 270 and 63.3 mV at 10 mA cm-2, along with low Tafel slopes of 51.6 and 62.0 mV dec-1. Furthermore, the Se-CoMoO4 couple electrolyzer merely requires a cell voltage of 1.48 V to achieve 10 mA cm-2 current density and presents no apparent attenuation for 30 h. This investigation declares that the hybridization of transition bimetallic oxide with nonmetallic adulteration can afford a tactic for the preparation of bifunctional non-precious metal-based electrocatalysts.

Advances in CAR-NK cell therapy for hematological malignancies.

Chimeric antigen receptor T (CAR-T) cell therapy has revolutionized the treatment of hematological malignancies, demonstrably improving patient outcomes and prognosis. However, its application has introduced new challenges, such as safety concerns, off-target toxicities, and significant costs. Natural killer (NK) cells are crucial components of the innate immune system, capable of eliminating tumor cells without prior exposure to specific antigens or pre-activation. This inherent advantage complements the limitations of T cells, making CAR-NK cell therapy a promising avenue for hematological tumor immunotherapy. In recent years, preclinical and clinical studies have yielded preliminary evidence supporting the safety and efficacy of CAR-NK cell therapy in hematological malignancies, paving the way for future advancements in immunotherapy. This review aims to succinctly discuss the characteristics, significant therapeutic progress, and potential challenges associated with CAR-NK cell therapy.

Bencaosome [16:0 Lyso PA+XLGB28-sRNA] improves osteoporosis by simultaneously promoting osteogenesis and inhibiting osteoclastogenesis in mice.

Osteoporosis (OP) is a systemic metabolic bone disease resulting in reduced bone strength and increased susceptibility to fractures, making it a significant public health and economic problem worldwide. The clinical use of anti-osteoporosis agents is limited because of their serious side effects or the high cost of long-term use. The Xianlinggubao (XLGB) formula is an effective traditional Chinese herbal medicine commonly used in orthopedics to treat osteoporosis; however, its mechanism of action remains unclear. In this study, we screened 40 small RNAs derived from XLGB capsules and found that XLGB28-sRNA targeting TNFSF11 exerted a significant anti-osteoporosis effect in vitro and in vivo by simultaneously promoting osteogenesis and inhibiting osteoclastogenesis. Oral administration of bencaosome [16:0 Lyso PA+XLGB28-sRNA] effectively improved bone mineral density and reduced the damage to the bone microstructure in mice. These results suggest that XLGB28-sRNA may be a novel oligonucleotide drug that promotes osteogenesis and inhibits osteoclastogenesis in mice.

Population structure and selection signal analysis of indigenous sheep from the southern edge of the Taklamakan Desert.

Analyzing the genetic diversity and selection characteristics of sheep (Ovis aries) holds significant value in understanding their environmental adaptability, enhancing breeding efficiency, and achieving effective conservation and rational utilization of genetic resources. In this study, we utilized Illumina Ovine SNP 50 K BeadChip data from four indigenous sheep breeds from the southern margin of the Taklamakan Desert (Duolang sheep: n = 36, Hetian sheep: n = 74, Kunlun sheep: n = 27, Qira black sheep: n = 178) and three foreign meat sheep breeds (Poll Dorset sheep: n = 105, Suffolk sheep: n = 153, Texel sheep: n = 150) to investigate the population structure, genetic diversity, and genomic signals of positive selection within the indigenous sheep. According to the Principal component analysis (PCA), the Neighbor-Joining tree (NJ tree), and Admixture, we revealed distinct clustering patterns of these seven sheep breeds based on their geographical distribution. Then used Cross Population Extended Haplotype Homozygosity (XP-EHH), Fixation Index (FST), and Integrated Haplotype Score (iHS), we identified a collective set of 32 overlapping genes under positive selection across four indigenous sheep breeds. These genes are associated with wool follicle development and wool traits, desert environmental adaptability, disease resistance, reproduction, and high-altitude adaptability. This study reveals the population structure and genomic selection characteristics in the extreme desert environments of native sheep breeds from the southern edge of the Taklimakan Desert, providing new insights into the conservation and sustainable use of indigenous sheep genetic resources in extreme environments. Additionally, these findings offer valuable genetic resources for sheep and other mammals to adapt to global climate change.

Co-administration of GnRH-agonist and hCG (double trigger) for final oocyte maturation increases the number of top-quality embryos in patients undergoing IVF/ICSI cycles.

BACKGROUND: The utilization of a double trigger, involving the co-administration of gonadotropin-releasing hormone agonist (GnRH-a) and human chorionic gonadotropin (hCG) for final oocyte maturation, is emerging as a novel approach in gonadotropin-releasing hormone antagonist (GnRH-ant) protocols during controlled ovarian hyperstimulation (COH). This protocol involves administering GnRH-a and hCG 40 and 34 h prior to ovum pick-up (OPU), respectively. This treatment modality has been implemented in patients with low/poor oocytes yield. This study aimed to determine whether the double trigger could improve the number of top-quality embryos (TQEs) in patients with fewer than three TQEs. METHODS: The stimulation characteristics of 35 in vitro fertilization (IVF) cycles were analyzed. These cycles were triggered by the combination of hCG and GnRHa (double trigger cycles) and compared to the same patients' previous IVF attempt, which utilized the hCG trigger (hCG trigger control cycles). The analysis involved cases who were admitted to our reproductive center between January 2018 and December 2022. In the hCG trigger control cycles, all 35 patients had fewer than three TQEs. RESULTS: Patients who received the double trigger cycles yielded a significantly higher number of 2PN cleavage embryos (3.54 ± 3.37 vs. 2.11 ± 2.15, P = 0.025), TQEs ( 2.23 ± 2.05 vs. 0.89 ± 0.99, P < 0.001), and a simultaneously higher proportion of the number of cleavage stage embryos (53.87% ± 31.38% vs. 39.80% ± 29.60%, P = 0.043), 2PN cleavage stage embryos (43.89% ± 33.01% vs. 27.22% ± 27.13%, P = 0.014), and TQEs (27.05% ± 26.26% vs. 14.19% ± 19.76%, P = 0.019) to the number of oocytes retrieved compared with the hCG trigger control cycles, respectively. The double trigger cycles achieved higher rates of cumulative clinical pregnancy (20.00% vs. 2.86%, P = 0.031), cumulative persistent pregnancy (14.29% vs. 0%, P < 0.001), and cumulative live birth (14.29% vs. 0%, P < 0.001) per stimulation cycle compared with the hCG trigger control cycles. CONCLUSION: Co-administration of GnRH-agonist and hCG for final oocyte maturation, 40 and 34 h prior to OPU, respectively (double trigger) may be suggested as a valuable new regimen for treating patients with low TQE yield in previous hCG trigger IVF/intracytoplasmic sperm injection (ICSI) cycles.

Anticancer activity of Araguspongine C via inducing apoptosis, and inhibition of oxidative stress, inflammation, and EGFR-TK in human lung cancer cells: An in vitro and in vivo study.

The advanced non-small cell lung cancer (NSCLC) that harbors epidermal growth factor receptor (EGFR) mutations has put a selective pressure on the discovery and development of newer EGFR inhibitors. Therefore, the present study intends to explore the pharmacological effect of Araguspongine C (Aragus-C) as anticancer agent against lung cancer. The effect of Aragus-C was evaluated on the viability of the A549 and H1975 cells. Further biochemical assays were performed to elaborate the effect of Aragus-C, on the apoptosis, cell-cycle analysis, and mitochondrial membrane potential in A549 cells. Western blot analysis was also conducted to determine the expression of EGFR in A549 cells. Tumor xenograft mice model from A549 cells was established to further elaborate the pharmacological activity of Aragus-C. Results suggest that Aragus C showed significant inhibitory activity against A549 cells as compared to H1975 cells. It has been found that Aragus-C causes the induction of apoptosis and promotes cell-cycle arrest at the G2/M phase of A549 cells. It also showed a reduction in the overexpression of EGFR in A549 cells. In tumor xenograft mice model, it showed a significant reduction of tumor volume in a dose-dependent manner, with maximum inhibitory activity was reported by the 8 mg/kg treated group. It also showed significant anti-inflammatory and antioxidant activity by reducing the level of TNF-α, IL-1ß, IL-6, and MDA, with a simultaneous increase of superoxide dismutase and glutathione peroxidase. We have demonstrated the potent anti-lung cancer activity of Aragus-C, and it may be considered as a potential therapeutic choice for NSCLC treatment.

Acupuncture and moxibustion treatment for breast cancer-related lymphoedema： a systematic review and Meta-analysis. / é’ˆç¸æ²»ç–—ä¹³è ºç™Œæ·‹å·´æ°´è‚¿çš„ç³»ç»Ÿè¯„ä»·å’ŒMeta分析.

OBJECTIVES: To evaluate the efficacy of acupuncture in treating breast cancer-related lymphedema (BCRL) by using systematic review and Meta analysis method. METHODS: Searching CNKI, Wanfang Data Knowledge Service Platform, VIP Chinese Journal Service Platform, Chinese Biomedical Literature Database, PubMed, Cochrane Library, Embase and Web of Science, the randomized controlled trials (RCTs) literature of acupuncture for BCRL was collected from the establishment of the databases to October 1st, 2023. After data extraction and risk of bias evaluation of the included literature, Meta-analysis was performed using RevMan5.4 software. RESULTS: A total of 14 RCTs with 952 patients were included. The Meta-analysis results showed that compared with comprehensive decongestive therapy (CDT), CDT-associated methods and other interventions of the contro group, acupuncture was able to decrease the circumference of the proximal 10 cm to elbow crease (MD=-1.95, P=0.000 5), reduce the difference in arm circumference (MD=-1.30, P<0.000 01), and increase the effective index (MD=27.47, P<0.000 01；RR=1.23, P=0.000 5)；acupuncture improves the range of motion(ROM) scores of shoulder joint in four areas：anteflexion(SMD=0.47, P=0.04), posterior extension (SMD=0.87, P<0.000 01), abduction (SMD=0.48, P=0.03), and adduction (SMD=0.72, P=0.000 5)；acupuncture also could alleviate pain and improve visual analog scale (VAS) scores (MD=-1.15, P<0.000 01). No serious adverse reactions were reported in the literatures. CONCLUSIONS: Acupuncture can effectively improve the degree of limb edema and subjective symptoms in BCRL patients.

A mussel-inspired, antibacterial, antioxidant, injectable composite hydrogel for the sustain delivery of salvianolic acid B for the treatment of frozen shoulder.

Frozen shoulder (FS) manifests as progressively worsening pain and a reduction in shoulder range of motion (ROM). Salvianolic acid B (SaB) is recently expected to be used in the treatment of fibrosis diseases including FS. We firstly demonstrate that SaB can effectively hinder the progression of oxidative stress, inflammation, and pathological fibrosis within the synovial tissue in FS, potentially leading to the reduction or reversal of capsule fibrosis and joint stiffness. For further clinical application, we design and synthesize a novel, superior, antioxidant and antibacterial CSMA-PBA/OD-DA (CPDA) hydrogel for the delivery of SaB. In vitro experiments demonstrate that the CPDA hydrogel exhibits excellent biocompatibility and rheological properties, rendering it suitable for intra-articular injections. Upon injection into the contracted joint cavity of FS model rat, the SaB-CPDA hydrogel accelerate the recovery of ROM and exhibit superior anti-fibrosis effect, presenting the promise for the treatment of FS in vivo.

Progress on immuno-microenvironment and immune-related therapies in patients with pseudomyxoma peritonei.

Pseudomyxoma peritonei (PMP) is an indolent malignant syndrome. The standard treatment for PMP is cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy (CRS + HIPEC). However, the high recurrence rate and latent clinical symptoms and signs are major obstacles to further improving clinical outcomes. Moreover, patients in advanced stages receive little benefit from CRS + HIPEC due to widespread intraperitoneal metastases. Another challenge in PMP treatment involves the progressive sclerosis of PMP cell-secreted mucus, which is often increased due to activating mutations in the gene coding for guanine nucleotide-binding protein alpha subunit (GNAS). Consequently, the development of other PMP therapies is urgently needed. Several immune-related therapies have shown promise, including the use of bacterium-derived non-specific immunogenic agents, radio-immunotherapeutic agents, and tumor cell-derived neoantigens, but a well-recognized immunotherapy has not been established. In this review the roles of GNAS mutations in the promotion of mucin secretion and disease development are discussed. In addition, the immunologic features of the PMP microenvironment and immune-associated treatments are discussed to summarize the current understanding of key features of the disease and to facilitate the development of immunotherapies.

Feasibility of implementing a remote system for lymphoedema conservative therapy: a case study.

BACKGROUND: Poor access to lymphoedema specialists and communication between them and patients prevents appropriate lymphoedema management. Therefore, development and dissemination of remote systems is necessary to improve care in rural areas with limited medical personnel or access to medical coordination. AIMS: The authors evaluated the elements required for providing patient education on conservative therapy for lymphoedema, to determine the feasibility of remote management. METHODS: The study involved connecting a health professional in a local clinic (point A) treating a patient with lymphoedema, who was present alongside the clinician, with a specialist certified lymphoedema therapist (CLT) located remotely in a university (point B). FINDINGS: The CLT was able to greet, interview and provide guidance to the patient on conservative therapy. Direct contact with the patient was not possible, which limited visualisation, palpation, leg circumference measurement, and lymphatic drainage management. CONCLUSION: The findings suggest that remote a lymphoedema management approach involving conservative therapy benefits both patients and health professionals, particularly in rural regions. Future studies are needed to confirm the effectiveness of this approach to confirm adequate treatment.

Histopathological growth pattern and vessel co-option in intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) exhibits different blood imaging features and prognosis depending on histology. To clarity histopathological growth patterns (HGPs) and vascularization processes of iCCA, we collected 145 surgical specimens and histologically classified them into large bile duct (LBD) (20 cases), small bile duct (SBD) (54), cholangiolocarcinoma (CLC) (35), combined SBD-CLC (cSBD-CLC) (26), and ductal plate malformation (DPM) (10) (sub)types. According to the invasive pattern at the interface between tumor and adjacent background liver, HGPs were classified into desmoplastic, pushing, and replacing HGPs. Desmoplastic HGP predominated in LBD type (55.5%), while replacing HGP was common in CLC (82.9%) and cSBD-CLC (84.6%) subtypes. Desmoplastic HGP reflected angiogenesis, while replacing HGP showed vessel co-option in addition to angiogenesis. By evaluating microvessel density (MVD) using vascular markers, ELTD1 identified vessel co-option and angiogenesis, and ELTD1-positive MVD at invasive margin in replacing HGP was significantly higher than those in desmoplastic and pushing HGPs. REDD1, an angiogenesis-related marker, demonstrated preferably higher MVD in the tumor center than in other areas. iCCA (sub)types and HGPs were closely related to vessel co-option and immune-related factors (lymphatic vessels, lymphocytes, and neutrophils). In conclusion, HGPs and vascular mechanisms characterize iCCA (sub)types and vessel co-option linked to the immune microenvironment.

Solid fuel use and low birth weight: a systematic review and meta-analysis.

Solid fuel use is increasingly linked to low birth weight (LBW), but conclusions were inconsistent. We aimed to summarize the association between solid fuel use and LBW. Twenty-one studies that met the inclusion criteria were identified through PubMed, Qvid Medline, and Web of Science databases. The final search occurred on March 20, 2024. Summary relative effect and 95 % confidence intervals were estimated with a random-effects model. Subgroup analyses and sensitivity analyses were performed to investigate possible sources of heterogeneity and to test the stability of the results. Nineteen studies evaluated the association between solid fuel use in pregnant woman and LBW (1.188 for solid fuels: 1.055 to 1.322). No significant heterogeneity was identified among the included studies (p=0.010, Tau2=0.02, I2=48.1 %). Subgroup analysis found positive correlations for Asia, data years prior to 2014, and rural studies (1.245 for Asia: 1.077 to 1.412; Tau2=0.03, I2=56.0 %; 1.243 for data years prior to 2014: 1.062 to 1.424; Tau2=0.04, I2=60.98 %; 1.514 for rural: 1.258 to 1.771; Tau2=0.00, I2=0.0 %). Our meta-analysis showed that solid fuel use in pregnant women had an impact on LBW. Measures and policies are also needed to promote energy conversion and to limit and reduce the use of solid fuels.