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Purpose: To identify risk factors for vision recovery in indirect traumatic optic neuropathy (TON) and to analyze the outcomes associated with surgical treatment for TON., Methods: Between 2020 and 2023, a total of 105 patients diagnosed with traumatic optic neuropathy (TON) at Shanghai Ninth People's Hospital and Shanghai Minhang Hospital were included in a retrospective study. These individuals underwent optic nerve decompression surgery as part of their treatment. To collect comprehensive data, both preoperative and postoperative information was gathered. For analytical purposes, only those patients who had a minimum of one month follow-up post-treatment were considered. The statistical analysis incorporated the use of median values, odds ratios (OR), and 95% confidence intervals (CI) to interpret the data. Any p -values less than 0.05 were deemed to indicate statistical significance, underlining the rigorous criteria set for this study., Results: A total of 105 patients, with a mean age of 31.8 ± 14.9 years, met the inclusion criteria; 89.5% (94) were men, and 10.5% (11) were women. The median time to seek medical attention after injury was 4 days (range: 1 to 15 days). Prognostic factors associated with visual acuity (VA) improvement included a gradual VA loss pattern (OR: 2.22, 95% CI: 0.91-5.67, p  = 0.045), while canal fractures (OR: 0.31, 95% CI: 0.095-0.933, p  = 0.019) significantly correlated with poor VA outcomes., Conclusions: This study suggested that surgical interventions benefit TON patients with low vision. Gradual VA loss, rather than sudden loss after injury, may be a potential prognostic factor for favorable VA outcomes, while canal fractures, as detected on computed tomography (CT) imaging-especially complex canal fractures, are associated with poor VA outcomes. In the future, more definitive prospective treatment trials are required to identify optimal treatment strategies for TON.

Phosphatidylethanolamine binding protein (PEBP) family plays important roles in multiple developmental processes in plants. In this study, a total of 11 PEBP gene family members were identified from the mango (Mangifera indica L.) genome, and these proteins were divided into three subfamilies based on their phylogenetic relationships: TERMINAL FLOWER 1 (TFL1)-like, MOTHER OF FT AND TFL (MFT)-like, and FLOWERING LOCUS T (FT)-like. Expression analysis revealed that MiFT1a, MiFT1b and MiFT2 were expressed mainly in leaves, whereas MiFT3 and MiFT4 were expressed mainly in embryos. The overexpression of MiFTs significantly promoted early flowering under both long- and short-day conditions. Interestingly, it still significantly promoted early flowering at 16 °C and 28 °C, with MiFT1a exhibiting the most significant, followed by MiFT1b and MiFT2. Additionally, the expression level of MiFT3 is related to the embryonic development of mango. Further studies revealed that overexpression of MiFT3 inhibited seed germination in transgenic Arabidopsis lines. In addition, the MiFT1a and MiFT1b transgenic lines did not respond to abiotic stress, while MiFT2, MiFT3 and MiFT4 enhanced resistance to salt or drought stress in Arabidopsis. Yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays revealed that MiFTs can interact with flower related and multiple stress proteins, such as bZIP protein (MiFD), 14-3-3 protein, zinc finger protein (MiZFP4), RING zinc-finger protein (MiRZFP34), and phosphatase 2C (MiPP2C25A and MiPP2C25B). These results indicate that FT subfamily not only regulates flowering but also participates in stress response, but there are differences in the function among these genes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In eukaryotes, the localization of small ribosomal subunits to mRNA transcripts requires the translation of Kozak elements at the starting site. The sequence of Kozak elements affects the translation efficiency of protein synthesis. However, whether the upstream nucleotide of Kozak sequence affects the expression of recombinant proteins in Chinese hamster ovary (CHO) cells remains unclear. In order to find the optimal sequence to enhance recombinant proteins expression in CHO cells, -10 to +4 sequences around ATG in 100 CHO genes were compared, and the extended Kozak elements with different translation intensities were constructed. Using the classic Kozak element as control, the effects of optimized extended Kozak elements on the secreted alkaline phosphatase (SEAP) and human serum albumin (HSA) gene were studied. The results showed that the optimized extended Kozak sequence can enhance the stable expression level of recombinant proteins in CHO cells. Furthermore, it was found that the increased expression level of the recombinant protein was not related with higher transcription level. In summary, optimizing extended Kozak elements can enhance the expression of recombinant proteins in CHO cells, which contributes to the construction of an efficient expression system for CHO cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Gibberellic acids (GAs) are a group of endogenous phytohormones that play important roles in plant growth and development. SLENDER RICE (SLR) serves as a vital component of the DELLA gene family, which plays an irreplaceable role in regulating plant flowering and height, as well as stress responses. SLR gene has not been reported in mango, and its function is unknown. In present study, two DELLA subfamily genes MiSLR1 and MiSLR2 were identified from mango. MiSLR1 and MiSLR2 were highly expressed in the stems of the juvenile stage, but were expressed at a low level in flower buds and flowers. Gibberellin treatment could up-regulate the expression of MiSLR1 and MiSLR2 genes, but gibberellin biosynthesis inhibitor prohexadione-calcium (Pro-Ca) and paclobutrazol (PAC) treatments significantly down-regulated the expression of MiSLR1, while MiSLR2 was up-regulated. The expression levels of MiSLR1 and MiSLR2 were up-regulated under both salt and drought treatments. Overexpression of MiSLR1 and MiSLR2 genes significantly resulted early flowering in transgenic Arabidopsis and significantly up-regulated the expression levels of endogenous flower-related genes, such as SUPPRESSOR OF CONSTANS1 (SOC1), APETALA1 (AP1), and FRUITFULL (FUL). Interestingly, MiSLR1 significantly reduced the height of transgenic plants, while MiSLR2 gene increased. Overexpression of MiSLR1 and MiSLR2 increased seed germination rate, root length and survival rate of transgenic plants under salt and drought stress. Physiological and biochemical detection showed that the contents of proline (Pro) and superoxide dismutase (SOD) were significantly increased, while the contents of malondialdehyde (MDA) and H 2 O 2 were significantly decreased. Additionally, protein interaction analysis revealed that MiSLR1 and MiSLR2 interacted with several flowering-related and GA-related proteins. The interaction between MiSLR with MiGF14 and MiSOC1 proteins was found for the first time. Taken together, the data showed that MiSLR1 and MiSLR2 in transgenic Arabidopsis both regulated the flowering time and plant height, while also acting as positive regulators of abiotic stress responses., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The clinical translation of tumor hypoxia intervention modalities still falls short of expectation, restricted by poor biocompatibility of oxygen-carrying materials, unsatisfactory oxygen loading performance, and abnormally high cellular oxygen consumption-caused insufficient hypoxia relief. Herein, a carrier-free oxygen nano-tank based on modular fluorination prodrug design and co-assembly nanotechnology is elaborately exploited, which is facilely fabricated through the molecular nanoassembly of a fluorinated prodrug (FSSP) of pyropheophorbide a (PPa) and an oxygen consumption inhibitor (atovaquone, ATO). The nano-tank adeptly achieves sufficient oxygen enrichment while simultaneously suppressing oxygen consumption within tumors for complete tumor hypoxia alleviation. Significant, the fluorination module in FSSP not only confers favorable co-assemblage of FSSP and ATO, but also empowers the nanoassembly to readily carry oxygen. As expected, it displays excellent oxygen carrying capacity, favorable pharmacokinetics, on-demand laser-triggerable ATO release, closed-loop tumor hypoxia relief, and significant enhancement to PPa-mediated PDT in vitro and in vivo. This study provides a novel nanotherapeutic paradigm for tumor hypoxia intervention-enhanced cancer therapy., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background and Purpose: This study aimed to investigate the effect of collateral circulation on the outcomes of thrombectomy versus medical management alone in basilar artery occlusion (BAO) patients with varying stroke severities., Methods: Data from the ATTENTION cohort were used to perform a post-hoc analysis comparing the outcomes of thrombectomy with medical management in BAO patients with varying degrees of collateral circulation and stroke severity. Basilar Artery on Computed Tomography Angiography (BATMAN) scores were used to quantify the collateral circulation, and the effect was estimated through a primary outcome of 90-day functional independence (modified Rankin Scale score, mRS ≤2). Favorable versus unfavorable BATMAN scores were analyzed as both continuous and categorical variables, and an adjusted multivariate regression model was applied., Results: Among 221 BAO patients, thrombectomy significantly improved functional independence compared to medical management in patients with favorable BATMAN scores (aOR 7.75, 95% CI 2.78-26.1), but not in those with unfavorable BATMAN scores (aOR 1.33, 95% CI 0.28-6.92; p interaction  = 0.028). When treated as a continuous variable, increased BATMAN score was found to be associated with a higher likelihood of functional independence in the thrombectomy group (aOR 1.97, 95% CI 1.44-2.81; p interaction  = 0.053). In severe stroke patients with higher BATMAN scores (National Institutes of Health Stroke Scale (NIHSS) ≥21), we identified a significant interaction for treatment effect with thrombectomy compared to medical management (p interaction  = 0.042)., Conclusion: An increased BATMAN score was significantly associated with a higher probability of functional independence after thrombectomy than after medical management, particularly in patients with severe BAO., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Iron contributes to tumor initiation and progression; however, excessive intracellular free Fe 2+ can be toxic to cancer cells. Our findings confirmed that multiple myeloma (MM) cells exhibited elevated intracellular iron levels and increased ferritin, a key protein for iron storage, compared with normal cells. Interestingly, Bortezomib (BTZ) was found to trigger ferritin degradation, increase free intracellular Fe 2+ , and promote ferroptosis in MM cells. Subsequent mechanistic investigation revealed that BTZ effectively increased NCOA4 levels by preventing proteasomal degradation in MM cells. When we knocked down NCOA4 or blocked autophagy using chloroquine, BTZ-induced ferritin degradation and the increase in intracellular free Fe 2+ were significantly reduced in MM cells, confirming the role of BTZ in enhancing ferritinophagy. Furthermore, the combination of BTZ with RSL-3, a specific inhibitor of GPX4 and inducer of ferroptosis, synergistically promoted ferroptosis in MM cell lines and increased cell death in both MM cell lines and primary MM cells. The induction of ferroptosis inhibitor liproxstatin-1 successfully counteracted the synergistic effect of BTZ and RSL-3 in MM cells. Altogether, our findings reveal that BTZ elevates intracellular free Fe 2+ by enhancing NCOA4-mediated ferritinophagy and synergizes with RSL-3 by increasing ferroptosisin MM cells., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Chemodynamic therapy (CDT) has emerged as a transformative paradigm in the realm of reactive oxygen species -mediated cancer therapies, exhibiting its potential as a sophisticated strategy for precise and effective tumor treatment. CDT primarily relies on metal ions and hydrogen peroxide to initiate Fenton or Fenton-like reactions, generating cytotoxic hydroxyl radicals. Its notable advantages in cancer treatment are demonstrated, including tumor specificity, autonomy from external triggers, and a favorable side-effect profile. Recent advancements in nanomedicine are devoted to enhancing CDT, promising a comprehensive optimization of CDT efficacy. This review systematically elucidates cutting-edge achievements in chemodynamic nanotherapeutics, exploring strategies for enhanced Fenton or Fenton-like reactions, improved tumor microenvironment modulation, and precise regulation in energy metabolism. Moreover, a detailed analysis of diverse CDT-mediated combination therapies is provided. Finally, the review concludes with a comprehensive discussion of the prospects and intrinsic challenges to the application of chemodynamic nanotherapeutics in the domain of cancer treatment., (© 2024 Wiley‐VCH GmbH.)

The intracellular journey of extracellular vesicles (EVs) cannot be ignored in various biological pathological processes. In this review, the biogenesis, biological functions, uptake pathways, intracellular trafficking routes, and biomedical applications of EVs were highlighted. Endosomal escape is a unique mode of EVs release. When vesicles escape from endosomes, they avoid the fate of fusing with lysosomes and being degraded, thus having the opportunity to directly enter the cytoplasm or other organelles. This escape mechanism is crucial for EVs to deliver specific signals or substances. The intracellular trafficking of EVs after endosomal escape is a complex and significant biological process that involves the coordinated work of various cellular structures and molecules. Through the in-depth study of this process, the function and regulatory mechanism of EVs are fully understood, providing new dimensions for future biomedical diagnosis and treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Metabolic dysfunction-associated steatohepatitis (MASH) poses challenges for targeted delivery and retention of therapeutic proteins due to excess extracellular matrix (ECM). Here we present a new approach to treat MASH, termed "Fibrosis overexpression and retention (FORT)". In this strategy, we design (1) retinoid-derivative lipid nanoparticle (LNP) to enable enhanced mRNA overexpression in fibrotic regions, and (2) mRNA modifications which facilitate anchoring of therapeutic proteins in ECM. LNPs containing carboxyl-retinoids, rather than alcohol- or ester-retinoids, effectively deliver mRNA with over 10-fold enhancement of protein expression in fibrotic livers. The carboxyl-retinoid rearrangement on the LNP surface improves protein binding and membrane fusion. Therapeutic proteins are then engineered with an endogenous collagen-binding domain. These fusion proteins exhibit increased retention in fibrotic lesions and reduced systemic toxicity. In vivo, fibrosis-targeting LNPs encoding fusion proteins demonstrate superior therapeutic efficacy in three clinically relevant male-animal MASH models. This approach holds promise in fibrotic diseases unsuited for protein injection., (© 2024. The Author(s).)

Importance: In several randomized clinical trials, endovascular thrombectomy led to better functional outcomes than conventional treatment at 90 days poststroke in patients with acute basilar artery occlusion. However, the long-term clinical outcomes of these patients have not been well delineated., Objective: To evaluate 1-year clinical outcomes in patients with acute basilar artery occlusion following endovascular thrombectomy vs control., Design, Setting, and Participants: This study is an extension of the ATTENTION trial, a multicenter, randomized clinical trial. Patients were included between February 2021 and January 2022, with 1-year follow-up through April 2023. This multicenter, population-based study was conducted at 36 comprehensive stroke sites. Patients with acute basilar artery occlusion within 12 hours of estimated symptom onset were included. Of the 342 patients randomized in the ATTENTION trial, 330 (96.5%) had 1-year follow-up information available., Exposures: Endovascular thrombectomy (thrombectomy group) vs best medical treatment (control group)., Main Outcomes and Measures: The primary outcome was defined as a score of 0 to 3 on the modified Rankin Scale (mRS) at 1 year. Secondary outcomes were functional independence (mRS score 0-2), excellent outcome (mRS score 0-1), level of disability (distribution of all 7 mRS scores), mortality, and health-related quality of life at 1 year., Results: Among 330 patients who had 1-year follow-up data, 227 (68.8%) were male, and the mean (SD) age was 67.0 (10.7) years. An mRS score 0 to 3 at 1 year was achieved by 99 of 222 patients (44.6%) in the thrombectomy group and 21 of 108 (19.4%) in the control group (adjusted rate ratio, 2.23; 95% CI, 1.51-3.29). Mortality at 1 year compared with 90 days was more frequent in both the thrombectomy group (101 of 222 [45.5%] vs 83 of 226 [36.7%]) and the control group (69 of 108 [63.9%] vs 63 of 114 [55.3%]). Excellent outcome (mRS score 0-1) at 1 year compared with 90 days increased in the thrombectomy group (62 of 222 [27.9%] vs 45 of 226 [19.9%]) but not in the control group (9 of 108 [8.3%] vs 9 of 114 [7.9%]) resulting in a magnified treatment benefit., Conclusions and Relevance: Among patients with basilar artery occlusion within 12 hours of onset, the benefits of endovascular thrombectomy at 1 year compared with 90 days were sustained for favorable (mRS score 0-3) outcome and enhanced for excellent (mRS score 0-1) outcome.

Background and Objectives: The percutaneous full-endoscopic C2 ganglionectomy (PEC2G), an innovative procedure developed for the surgical treatment of intractable occipital neuralgia, was firstly reported by us in 2021. However, a universally accepted and well-articulated protocol modality remains elusive. The primary objective of this anatomic investigation was to meticulously elucidate the standard procedural steps of PEC2G and assess the anatomic features supporting the safe implementation of PEC2G., Methods: Eighteen fresh adult cadavers were incorporated into this study. From this sample, 3 cadavers were subjected to bilateral PEC2G. Each procedure was documented and assessed, leading to the formulation of standard procedure criteria for PEC2G. Subsequently, 10 sets of anatomic parameters pertinent to this procedure were identified, quantified, and analyzed in 15 cadavers after complete bilateral endoscopic exposure of the C2 ganglion. An assessment of the technical feasibility and potential constraints associated with PEC2G was conducted, providing invaluable insights into the procedure's anatomic considerations., Results: All 3 cadavers successfully underwent the PEC2G without any observed complications, such as dura tears or vertebral artery injuries. The C2 inferior articular process emerged as the optimal bony target for puncture, with the C2 pedicle serving as the standard guiding landmark en route to the C2 ganglion. In the 15 cadavers subjected to the planned procedure, 10 sets of anatomic parameters were quantified, establishing a foundational understanding of the anatomy in the context of PEC2G procedure. The results demonstrated that the characteristic of anatomic data pertinent to surgical site supported the safe implementation of PEC2G., Conclusion: This study contributes the standard surgical steps and crucial anatomic parameters relevant to PEC2G. The characteristic of anatomic data bolsters the safety credentials of this technique, which offers a reliable approach to achieve C2 ganglionectomy. These insights undeniably establish a robust foundation for the ongoing refinement and broader adoption of PEC2G., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc on behalf of Congress of Neurological Surgeons.)

Small-molecule prodrug nanoassembly technology with a unique advantage in off-target toxicity reduction has been widely used for antitumor drug delivery. However, prodrug activation remains a rate-limiting step for exerting therapeutic actions, which requires to quickly reach the minimum valid concentrations of free drugs. Fortunately, we find that a natural compound (BL-193) selectively improves the chemotherapy sensitivity of breast cancer cells to podophyllotoxin (PPT) at ineffective dose concentrations. Based on this, we propose to combine prodrug nanoassembly with chemotherapy sensitization to fully unleash the chemotherapeutic potential of PPT. Specifically, a redox-sensitive prodrug (PSSF) of PPT is synthesized by coupling 9-fluorenyl-methanol (Fmoc-OH) with PPT linked via disulfide bond. Intriguingly, PSSF with a π-conjugated structure readily co-assembles with BL-193 into stable nanoassembly. Significantly, BL-193 serves as an excellent chemosensitizer that creates an ultra-low-dose chemotherapeutic window for PPT. Moreover, prodrug design and precise hybrid nanoassembly well manage off-target toxicity. As expected, such a BL-193-empowered prodrug nanoassembly elicits potent antitumor responses. This study offers a novel paradigm to magnify chemotherapy efficacy-toxicity benefits., Competing Interests: The authors declare that there is no conflicts of interest., (© 2024 Published by Elsevier B.V. on behalf of Shenyang Pharmaceutical University.)

The Pacific oyster Crassostrea gigas is renowned for its high zinc content, but the significant variation among individuals diminishes its value as a reliable source of zinc supplementation. The Zrt/Irt-like protein 1 (ZIP1), a pivotal zinc transporter that facilitates zinc uptake in various organisms, plays crucial roles in regulating zinc content. In the present study, polymorphisms of a ZIP1 gene in C. gigas (CgZIP1-II) were investigated, and their association with zinc content was evaluated through preliminary association analysis in 41 oysters and verification analysis in another 200 oysters. A total of 17 single nucleotide polymorphisms (SNPs) were identified in the exonic region of CgZIP1-II gene, with c.503A>G significantly associated with zinc content. Protein sequence and structure prediction showed that c.503A>G caused a p.Met110Val nonsynonymous mutation located in the metal-binding region of CgZIP1-II, which could influence its affinity for zinc ions, thereby modulating its zinc transport functionality. These results indicate the potential influence of CgZIP1-II polymorphisms on zinc content and provide candidate markers for selecting C. gigas with high zinc content., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The Pacific oyster Crassostrea gigas is rich in taurine, which is crucial for its adaptation to the fluctuating intertidal environment and presents significant potential in improving taurine nutrition and boosting immunity in humans. Cysteine dioxygenase (CDO) is a key enzyme involved in the initial step of taurine biosynthesis and plays a crucial role in regulating taurine content in the body. In the present study, polymorphisms of CDO gene in C. gigas (CgCDO) and their association with taurine content were evaluated in 198 individuals. A total of 24 single nucleotide polymorphism (SNP) loci were identified in the exonic region of CgCDO gene by direct sequencing. Among these SNPs, c.279G>A and c.287C>A were found to be significantly associated with taurine content, with the GG and AA genotype at the two loci exhibiting enhanced taurine accumulation (p < 0.05). Haplotype analysis revealed that the 279GG/287AA haplotype had the highest taurine content of 29.24 mg/g, while the 279AA/287CC haplotype showed the lowest taurine content of 21.19 mg/g. These results indicated that the SNPs of CgCDO gene could influence the taurine content in C. gigas and have potential applications in the selective breeding of high-taurine varieties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: This study compared the efficacy of oropharyngeal airways (OA) and nasopharyngeal airways (NA) in maintaining oxygenation during painless fiberoptic bronchoscopy (PFB) in patients sedated with remimazolam besylate., Methods: Two hundred and fifty-two patients were randomized to the OA or NA group. Remimazolam besylate was used for anesthesia induction and maintenance in both groups. We measured and recorded several physiological parameters, including mean arterial pressure, heart rate and oxygen saturation (SpO2), at various time points: before anesthesia (T1), after anesthesia induction (T2), immediately after the bronchoscope reached the trachea (T3), during the procedure (T4), and 5 min after transfer to the post-anesthesia care unit (T5). The incidence and frequency of hypoxemia, minimum SpO2 during the procedure and patient awakening time after flumazenil administration were also recorded. Additionally, the relationship between minimum SpO2 and body mass index (BMI) was investigated., Results: Patients in the NA group experienced a higher incidence of hypoxemia compared to the OA group. Patients in the OA group maintained higher SpO2 levels at T3 and had a higher minimum SpO2 during the procedure than the NA group. Furthermore, a significant negative correlation was observed between minimum SpO2 and BMI. Following flumazenil anesthesia reversal, nearly 97 % of patients awakened within 1 min., Conclusions: This study suggests that OA may provide a better safety profile than NA by preserving respiratory function during PFB., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: The purpose of this study was to perform a biomechanical analysis to compare different medial column fixation patterns for valgus pilon fractures in a case-based model., Methods: Based on the fracture mapping, 48 valgus pilon fracture models were produced and assigned into four groups with different medial column fixation patterns: no fixation (NF), K-wires (KW), intramedullary screws (IS), and locking compression plate (LCP). Each group contained wedge-in and wedge-out subgroups. After fixing each specimen on the machine, gradually increased axial compressive loads were applied with a load speed of one millimeter per minute. The maximum peak force was set at 1500 N. Load-displacement curves were generated and the axial stiffness was calculated. Five different loads of 200 N, 400 N, 600 N, 800 N, 1000 N were selected for analysis. The specimen failure was defined as resultant loading displacement over 3 mm., Results: For the wedge-out models, Group-IS showed less displacement (p < 0.001), higher axial stiffness (p < 0.01), and higher load to failure (p < 0.001) than Group-NF. Group-KW showed comparable displacement under loads of 200 N, 400 N and 600 N with both Group-IS and Group-LCP. For the wedge-in models, no statistical differences in displacement, axial stiffness, or load to failure were observed among the four groups. Overall, wedge-out models exhibited less axial stiffness than wedge-in models (all p < 0.01)., Conclusions: Functional reduction with stable fixation of the medial column is essential for the biomechanical stability of valgus pilon fractures and medial column fixation provides the enough biomechanical stability for this kind of fracture in the combination of anterolateral fixation. In detail, the K-wires can provide a provisional stability at an early stage. Intramedullary screws are strong enough to provide the medial column stability as a definitive fixation. In future, this technique can be recommended for medial column fixation as a complement for holistic stability in high-energy valgus pilon fractures., (© 2024. The Author(s).)

Background: Spinal cord stimulation is an established technique wherein diverse electrode types are strategically implanted within the spinal epidural space for neuromodulation. Traditional percutaneous puncture cylindrical electrodes (PEs) are predominantly implanted by interventionalists utilizing a percutaneous technique under the monitor of radiation, which is a nonvisualized procedure., Objective: Our study aimed to assess the feasibility of percutaneous endoscope-assisted visualized implantation approach for PEs, delineating its specific merits and demerits compared to the traditional method., Study Design: Laboratory study with Institutional Review Board Number B2023-056SETTING: Clinical Anatomy Research Center, Fudan University., Methods: Eight freshly procured adult cadavers (4 women and 4 men) were operated on in this study. They were divided into either Group A or Group B, each encompassing 4 cadavers. Group A was subjected to endoscope-assisted PEs implantation, whereas Group B followed the conventional PEs implantation route.In both groups the operative time of introducer needles placement (OTNP), total operative time (TOT), fluoroscopy time of introducer needles placement (FTNP), and total fluoroscopy time (TFT) were documented and analyzed. Furthermore, the precise positioning of the PEs and any ensuing complications were systematically examined., Results: Both Group A and Group B successfully executed all predetermined surgical steps. A total of 16 PEs were implanted (dual electrodes in each cadaver): 8 using the percutaneous endoscope-assisted visualized approach (Group A) and 8 via the traditional methodology (Group B). Group A's mean ± SD durations for OTNP, TOT, FTNP, and TFT were 10.25 ± 1.03 minutes, 31.63 ± 5.87 minutes, 4.58 ± 1.35 seconds, and 43.73 ± 14.46 seconds, respectively. In contrast, Group B exhibited mean ± SD times of 11.55 ± 2.81 minutes, 44.75 ± 7.85 minutes, 23.53 ± 4.16 seconds, and 66.30 ± 6.35 seconds for the same metrics. No discernible statistical difference in OTNP and TOT emerged between the groups. However, Group A demonstrated reduced durations for both FTNP and TFT compared to Group B. The optimal position of the PEs was verified via fluoroscopy, with no recorded instances of dura rupture. These outcomes suggest that this endoscope-assisted technique neither increases surgical time nor compromises efficacy. Instead, it leads to a marked reduction in fluoroscopic duration relative to the traditional methodology., Limitations: Anatomical study on a human cadaver, the quantity of cadavers, and the procedure's steep learning curve., Conclusion: With the assistance of percutaneous spinal endoscopy, introducer needles can be punctured through the ligamentum flavum at the anticipated interlaminar window locus under direct visualization, improving the convenience of the puncture and reducing fluoroscopic exposure. It is a viable alternative for surgeons from diverse training backgrounds to implant PEs, particularly benefiting those well-versed in endoscopic spine surgery techniques.

Photodynamic therapy (PDT), extensively explored as a non-invasive and spatio-temporal therapeutic modality for cancer treatment, encounters challenges related to the brief half-life and limited diffusion range of singlet oxygen. Lipid peroxides, formed through the oxidation of polyunsaturated fatty acids by singlet oxygen, exhibit prolonged half-life and potent cytotoxicity. Herein, we employed small molecule co-assembly technology to create nanoassemblies of pyropheophorbide a (PPa) and docosahexaenoic acid (DHA) to bolster PDT. DHA, an essential polyunsaturated fatty acid, co-assembled with PPa to generate nanoparticles (PPa@DHA NPs) without the need for additional excipients. To enhance the stability of these nanoassemblies, we introduced 20% DSPE-PEG 2k as a stabilizing agent, leading to the formation of PPa@DHA PEG 2k NPs. Upon laser irradiation, PPa-produced singlet oxygen swiftly oxidized DHA, resulting in the generation of cytotoxic lipid peroxides. This process significantly augmented the therapeutic efficiency of PDT. Consequently, tumor growth was markedly suppressed, attributed to the sensitizing and amplifying impact of DHA on PDT in a 4T1 tumor-bearing mouse model. In summary, this molecule-engineered nanoassembly introduces an innovative co-delivery approach to enhance PDT with polyunsaturated fatty acids., (© 2023. Controlled Release Society.)

Background: As the stages of the COVID-19 pandemic evolved, the symptoms of depression, anxiety, and insomnia have increasingly manifested among Chinese college students. The aim of this study is to investigate the relationships between these symptoms through network analysis among Chinese college students during COVID-19., Method: A three-wave cross-sectional survey was conducted at 22 colleges in Guangdong Province, involving 381,152 students during three specific time intervals: T1 (baseline, February 3 to 10, 2020), T2 (19 months after baseline, June 10 to 18, 2021), and T3 (37 months after baseline, March 15 to April 22, 2023). Depression (PHQ-9), anxiety (GAD-7), and insomnia (YSIS) were used separately. We analyzed two key network indices: "Expected influence" and "Bridge expected influence". Network stability was assessed through a case-dropping bootstrap program., Result: The effective sample sizes for the three periods were as follows: T1 - 164,101 (103,645 females, 63.2 %), T2 - 86,767 (52,146 females, 60.1 %), and T3 - 130,284 (76,720 females, 58.9 %). Across these three periods, the key central symptoms were "Fatigue" (PHQ4), "Restlessness" (GAD5), "Uncontrollable worrying" (GAD2), "Worry too much" (GAD3) and "Sleep insufficiency" (YSIS6). Notably, "Fatigue" (PHQ4), "Restlessness" (GAD5) and "Irritability" (GAD6) consistently served as bridge symptoms. In the T1 and T2 period, "Motor" (PHQ8) acted as a bridge symptom but weakened in T3., Conclusion: Throughout the three periods, the mental health issues among Chinese college students displayed characteristics of somatization within the depression-anxiety-insomnia comorbidity network. Over time, anxiety symptoms appeared to become more prominent. Consequently, this study highlights the importance of accurately identifying and promptly intervening in these core symptoms of mental health among college students, as these symptoms may evolve across different stages of a pandemic., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ferroptosis is identified as a potential target for anticancer therapy. However, most conventional ferroptosis inducers not only fail to trigger intracellular lipid peroxidation storm, but are also prone to cause ferroptosis-related toxicity through off-target destruction of intracellular antioxidant defense systems. Therefore, a potent and highly tumor-specific ferroptosis induction modality is desired. Herein, a self-cooperative nanomedicine for imaging-guided photothermal ferrotherapy, which is fabricated based on molecular nanoassembly (NA) of DiR (a photothermal probe) and ferrocene (Fc, a reactant of the Fenton reaction), is elaborately exploited. DiR-elicited hyperthermia induces both photothermal therapy (PTT) and a significant acceleration of the kinetics of the Fc-involved Fenton reaction, collaboratively causing a lipid peroxidation storm in tumor cells. In turn, plenty of lipid peroxides boost PTT through the downregulation of heat shock protein 90. As expected, such a self-cooperative NA demonstrates synergetic tumor eradication in the 4T1 breast tumor-bearing mice xenograft model. This study offers a novel nanotherapeutic paradigm for precise multimodal cancer therapy., (© 2024 Wiley‐VCH GmbH.)

Background: The utility of pre- and post-operative alpha-fetoprotein (AFP) and des-gamma (γ)-carboxy prothrombin (DCP) expression patterns and their dynamic changes as predictors of the outcome of hepatic resection for hepatocellular carcinoma (HCC) has yet to be well elucidated., Methods: From a multicenter database, AFP and DCP data during the week prior to surgery and the first post-discharge outpatient visit (within 1-2 months after surgery) were collected from patients with HCC who underwent hepatectomy. AFP-DCP expression patterns were categorized according to the number of positive tumor markers (AFP ≥ 20ng/mL, DCP ≥ 40mAU/mL), including double-negative, single-positive, and double-positive. Changes in the AFP-DCP expression patterns were delineated based on variations in the number of positive tumor markers when comparing pre- and post-operative patterns., Results: Preoperatively, 53 patients (8.3%), 337 patients (52.8%), and 248 patients (38.9%) exhibited double-negative, single-positive, and double-positive AFP-DCP expression patterns, respectively. Postoperatively, 463 patients (72.6%), 130 patients (20.4%), and 45 patients (7.0%) showed double-negative, single-positive, and double-positive AFP-DCP expression patterns, respectively. Survival analysis showed a progressive decrease in recurrence-free (RFS) and overall survival (OS) as the number of postoperative positive tumor markers increased (both P < 0.001). Multivariate analysis showed that postoperative AFP-DCP expression pattern, but not preoperative AFP-DCP expression pattern, was an independent risk factor for RFS and OS. Further analysis showed that for patients with positive preoperative markers, prognosis gradually improves as positive markers decrease postoperatively. In particular, when all postoperative markers turned negative, the prognosis was consistent with that of preoperative double-negative patients, regardless of the initial number of positive markers., Conclusions: AFP-DCP expression patterns, particularly postoperative patterns, serve as vital sources of information for prognostic evaluation following hepatectomy for HCC. Moreover, changes in AFP-DCP expression patterns from pre- to post-operation enable dynamic prognostic risk stratification postoperatively, aiding the development of individualized follow-up strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tang, Wu, Lin, Chen, Luo, Li, Fu, Zheng, You, You, You, Lin, Zhou, Lin and Zeng.)

Gastric cancer (GC) is a prevalent malignancy characterized by significant morbidity and mortality, yet its underlying pathogenesis remains elusive. The etiology of GC is multifaceted, involving the activation of oncogenes and the inactivation of antioncogenes. The ubiquitin-proteasome system (UPS), responsible for protein degradation and the regulation of physiological and pathological processes, emerges as a pivotal player in GC development. Specifically, the F-box protein (FBP), an integral component of the SKP1-Cullin1-F-box protein (SCF) E3 ligase complex within the UPS, has garnered attention for its prominent role in carcinogenesis, tumor progression, and drug resistance. Dysregulation of several FBPs has recently been observed in GC, underscoring their significance in disease progression. This comprehensive review aims to elucidate the distinctive characteristics of FBPs involved in GC, encompassing their impact on cell proliferation, apoptosis, invasive metastasis, and chemoresistance. Furthermore, we delve into the emerging role of FBPs as downstream target proteins of non-coding RNAs(ncRNAs) in the regulation of gastric carcinogenesis, outlining the potential utility of FBPs as direct therapeutic targets or advanced therapies for GC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Purpose: Radical surgery, the first-line treatment for patients with hepatocellular cancer (HCC), faces the dilemma of high early recurrence rates and the inability to predict effectively. We aim to develop and validate a multimodal model combining clinical, radiomics, and pathomics features to predict the risk of early recurrence., Materials and Methods: We recruited HCC patients who underwent radical surgery and collected their preoperative clinical information, enhanced computed tomography (CT) images, and whole slide images (WSI) of hematoxylin and eosin (H & E) stained biopsy sections. After feature screening analysis, independent clinical, radiomics, and pathomics features closely associated with early recurrence were identified. Next, we built 16 models using four combination data composed of three type features, four machine learning algorithms, and 5-fold cross-validation to assess the performance and predictive power of the comparative models., Results: Between January 2016 and December 2020, we recruited 107 HCC patients, of whom 45.8% (49/107) experienced early recurrence. After analysis, we identified two clinical features, two radiomics features, and three pathomics features associated with early recurrence. Multimodal machine learning models showed better predictive performance than bimodal models. Moreover, the SVM algorithm showed the best prediction results among the multimodal models. The average area under the curve (AUC), accuracy (ACC), sensitivity, and specificity were 0.863, 0.784, 0.731, and 0.826, respectively. Finally, we constructed a comprehensive nomogram using clinical features, a radiomics score and a pathomics score to provide a reference for predicting the risk of early recurrence., Conclusions: The multimodal models can be used as a primary tool for oncologists to predict the risk of early recurrence after radical HCC surgery, which will help optimize and personalize treatment strategies., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Patients suffering from sepsis-induced acute lung injury (ALI) exhibit a high mortality rate, and their prognosis is closely associated with infiltration of neutrophils into the lungs. In this study, we found a significant elevation of CD64 + neutrophils, which highly expressed p75 neurotrophin receptor (p75 NTR ) in peripheral blood of mice and patients with sepsis-induced ALI. p75 NTR+ CD64 + neutrophils were also abundantly expressed in the lung of ALI mice induced by lipopolysaccharide. Conditional knock-out of the myeloid lineage's p75 NTR gene improved the survival rates, attenuated lung tissue inflammation, reduced neutrophil infiltration and enhanced the phagocytic functions of CD64 + neutrophils. In vitro, p75 NTR+ CD64 + neutrophils exhibited an upregulation and compromised phagocytic activity in blood samples of ALI patients. Blocking p75 NTR activity by soluble p75 NTR extracellular domain peptide (p75 ECD -Fc) boosted CD64 + neutrophils phagocytic activity and reduced inflammatory cytokine production via regulation of the NF-κB activity. The findings strongly indicate that p75 NTR+ CD64 + neutrophils are a novel pathogenic neutrophil subpopulation promoting sepsis-induced ALI., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The purpose of this study is to compare the efficacy and safety of transarterial chemoembolization (TACE) alone with transarterial chemoembolization combined with the arterial infusion of bevacizumab (TACE + Bev) in patients with unresectable hepatocellular carcinoma (uHCC)., Methods: A retrospective analysis was conducted on 446 uHCC patients treated with TACE or TACE + Bev between January 2021 and March 2023. The study evaluated objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events in both treatment groups., Results: Finally, the TACE group comprised 295 patients, and the TACE + Bev group comprised 151 patients. Patients in the TACE + Bev group exhibited significantly prolonged median PFS (7.9 months vs. 10.3 months, P = 0.013) and median OS (16.1 months vs. 21.4 months, P = 0.041), improved ORR (26.8% vs. 37.7%, P = 0.017) and DCR (71.5% vs. 80.8%, P = 0.033) compared to the TACE group. Multifactorial Cox analysis identified alpha-fetoprotein (AFP) > 400 ng/ml as an independent prognostic factor for PFS and OS. Meanwhile, portal vein cancer thrombosis and distant metastasis are poor prognostic factors for OS. The overall incidence of adverse events was similar between the two groups., Conclusion: In comparison with the TACE group, the TACE + Bev group demonstrated efficacy in improving outcomes for patients with uHCC with a manageable safety profile., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Inflammatory dysregulation is intimately associated with the occurrence and progression of many life-threatening diseases. Accurate detection and timely therapeutic intervention on inflammatory dysregulation are crucial for the effective therapy of inflammation-associated diseases. However, the clinical outcomes of inflammation-involved disorders are still unsatisfactory. Therefore, there is an urgent need to develop innovative anti-inflammatory strategies by integrating emerging technological innovations with traditional therapeutics. Biomedical nanotechnology is one of the promising fields that can potentially transform the diagnosis and treatment of inflammation. In this review, we outline recent advances in biomedical nanotechnology for the diagnosis and treatment of inflammation, with special attention paid to nanosensors and nanoprobes for precise diagnosis of inflammation-related diseases, emerging anti-inflammatory nanotherapeutics, as well as nanotheranostics and combined anti-inflammatory applications. Moreover, the prospects and challenges for clinical translation of nanoprobes and anti-inflammatory nanomedicines are highlighted., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: This study aimed to assess the activity of apatinib plus toripalimab in the second line for patients with advanced gastric or esophagogastric junction cancer (GC/EGJC)., Methods: In this open-label, phase II, randomized trial, patients with advanced GC/EGJC who progressed after first-line chemotherapy were enrolled and received 250 mg apatinib per day plus 240 mg toripalimab on day 1 per 3 weeks (arm A) or physician's choice of chemotherapy (PC, arm B). The primary endpoint of this study was the 1-year survival rate. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and safety were assessed as secondary endpoints., Results: Twenty-five patients received apatinib plus toripalimab while 26 were enrolled in arm B. The 1-year survival rates of the 2 groups were 43.3% and 42.3%, respectively (P = .903). The PFS was 2.77 versus 2.33 months (P = .660). The OS was 8.30 versus 9.88 months (P = .539). An objective response was reported in 20.0% of patients in arm A compared to 26.9% in arm B (P = .368), respectively. A total of 6 (24.0%) patients experienced adverse events of grade ≥ 3 in arm A, while 9 (34.6%) patients suffered from adverse events of grade ≥ 3 in arm B. No drug-related deaths occurred in either group., Conclusion: Toripalimab plus apatinib treatment in second-line therapy of advanced GC/EGJC showed manageable toxicity but did not improve clinical outcomes relative to PC treatment (ClinicalTrials.gov Identifier: NCT04190745)., (© The Author(s) 2024. Published by Oxford University Press.)

Background: The impact of hepatic resection type on long-term oncological prognosis of patients with early-stage hepatocellular carcinoma (HCC) has not been systematically investigated. We sought to determine risk factors, recurrence patterns, and survival outcomes after anatomical resection (AR) versus non-anatomical resection (NAR) for early-stage HCC., Methods: From a prospectively collected multicenter database, consecutive patients undergoing curative hepatectomy for early-stage HCC were identified. Recurrence patterns, overall survival (OS), recurrence-free survival (RFS), and risk factors were investigated in patients undergoing AR versus NAR using propensity score matching (PSM), subgroup analysis, and COX regression analysis., Results: A total of 3585 patients with early-stage HCC were enrolled, including 1287 and 2298 in the AR and NAR groups, respectively. After PSM, the OS and RFS of patients in the AR group were 58.8% and 42.7%, which were higher than those in the NAR group (52.2% and 30.6%, both p < 0.01). The benefits of AR were consistent across most subgroup analyses of OS and RFS. Multivariable COX regression analysis showed that AR was independently associated with better OS and RFS. Notably, although recurrence patterns were comparable, the risk factors for recurrence were not identical for AR versus NAR. Microvascular invasion and narrow resection margin were only associated with a higher recurrence rate after NAR., Conclusions: This study demonstrated that AR decreases the risk of tumor recurrence and improves OS and RFS in patients with early-stage HCC. AR should be adopted as long as such a surgical maneuver is feasible for initial treatment of early-stage HCC., (© 2023. Asian Pacific Association for the Study of the Liver.)

Tapping into the innate immune system's power, nanovaccines can induce tumor-specific immune responses, which is a promising strategy in cancer immunotherapy. However, traditional vaccine design, requiring simultaneous loading of antigens and adjuvants, is complex and poses challenges for mass production. Here, we developed a tumor nanovaccine platform that integrates adjuvant functions into the delivery vehicle, using branched polyguanidine (PolyGu) nanovaccines. These nanovaccines were produced by modifying polyethylenimine (PEI) with various guanidine groups, transforming PEI's cytotoxicity into innate immune activation. The PolyGu nanovaccines based on poly(phenyl biguanidine ) (Poly-PBG) effectively stimulated dendritic cells, promoted their maturation via the TLR4 and NLRP3 pathways, and displayed robust in vivo immune activity. They significantly inhibited tumor growth and extended mouse survival. The PolyGu also showed promise for constructing more potent mRNA-based nanovaccines, offering a platform for personalized cancer vaccine. This work advances cancer immunotherapy toward potential clinical application by introducing a paradigm for developing self-adjuvanting nanovaccines.

SQUAMOSA promoter-binding protein-like (SPL) family genes play an important role in regulating plant flowering and resistance to stress. However, understanding the function of the SPL family in mango is still limited. In a previous study, two MiSPL3 genes, MiSPL3a and MiSPL3b (MiSPL3a/b), were identified in 'SiJiMi' mango and exhibited the highest expression in flowers at the initial flowering stage [24]. Therefore, in this study, we further investigated the expression pattern and gene function of MiSPL3a/b. The results showed that the expression of MiSPL3a was greatest at the end of floral bud differentiation, and MiSPL3b was expressed mainly during the flowering induction and vegetative growth stages. Subcellular localization showed that MiSPL3a/b localized to the nucleus. In addition, ectopic expression of MiSPL3a/b promoted earlier flowering in Arabidopsis thaliana by 3 d-6 d than in wild-type (WT) plants, which increased the expression of SUPPRESSOR OF CONSTANS1 (AtSOC1), FRUITFULL (AtFUL), and APETALA1 (AtAP1). MiSPL3a/b transgenic lines exhibited increased tolerance to drought, GA 3 , and abscisic acid (ABA) treatments but were sensitive to Pro-Ca treatment. Furthermore, protein interaction analysis revealed that MiSPL3a/b could interact with several stress-related proteins, flowering-related proteins, and the bridge protein 14-3-3. Taken together, MiSPL3a and MiSPL3b acted as positive regulators of flowering time and stress tolerance in transgenic Arabidopsis., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled “Overexpression of MiSPL3a and MiSPL3b confers early flowering and stress tolerance in Arabidopsis thaliana”. All authors have seen the manuscript and approved the submittal to your journal. None of the material in the paper has been published or is under consideration for publication elsewhere., (Copyright © 2024. Published by Elsevier B.V.)

The CONSTANS/CONSTANS-Like (CO/COL) family has been shown to play important roles in flowering, stress tolerance, fruit development and ripening in higher plants. In this study, three COL genes, MiCOL6, MiCOL7A and MiCOL7B, which each contain only one CCT domain, were isolated from mango (Mangifera indica), and their functions were investigated. MiCOL7A and MiCOL7B were expressed mainly at 20 days after flowering (DAF), and all three genes were highly expressed during the flowering induction period. The expression levels of the three genes were affected by light conditions, but only MiCOL6 exhibited a clear circadian rhythm. Overexpression of MiCOL6 promoted earlier flowering, while overexpression of MiCOL7A or MiCOL7B delayed flowering compared to that in the control lines of Arabidopsis thaliana under long-day (LD) and short-day (SD) conditions. Overexpressing MiCOL6, MiCOL7A or MiCOL7B in transgenic plants increased superoxide dismutase (SOD) and proline levels, decreased malondialdehyde (MAD) levels, and improved survival under drought and salt stress. In addition, yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) analyses showed that the MiCOL6, MiCOL7A and MiCOL7B proteins interact with several stress- and flower-related proteins. This work demonstrates the functions of MiCOL6, MiCOL7A and MiCOL7B and provides a foundation for further research on the role of mango COL genes in flowering regulation and the abiotic stress response., (© 2024 Scandinavian Plant Physiology Society.)

Global human population has increased dramatically over the past 50 years. As a result, marine fisheries and finfish aquaculture have become increasingly unsustainable, driving bivalve aquaculture to become an important food industry for the production of marine animal protein to support the growing market demand for animal protein. It is projected that the rate of bivalve aquaculture expansion will be greatly accelerated in the near future as the human population continues to increase. Although it is generally believed that unfed bivalve aquaculture has less impact on the environment than finfish aquaculture, the rapid expansion of bivalve aquaculture has raised concerns about its potential negative impact, especially on plankton and benthic community. Therefore, there is an urgent need to update the potential effects of bivalve aquaculture on plankton and benthic community. This article reviews the present state of knowledge on environmental issues related to bivalve aquaculture, and discusses potential mitigation measures for the environmental impacts induced by expansion of bivalve aquaculture. This review provides guidance for scientists and farm managers to clarify the current state of research and identify priority research needs for future bivalve aquaculture research. Therefore, specific management strategies can be formulated for the sustainable development and expansion of bivalve aquaculture., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Lumbar spinal stenosis (LSS) involves the narrowing of the spinal canal due to degenerative changes in the vertebral joints, intervertebral discs, and ligaments. LSS encompasses central canal stenosis (CCS), lateral recess stenosis (LRS), and intervertebral foramen stenosis (IFS). The utilization of lumbar endoscopic unilateral laminotomy for bilateral decompression (LE-ULBD) has gained popularity in the treatment of CCS and LRS. This popularity is attributed to the rapid development of endoscopic instruments and the progress of endoscopic philosophy. In this technical report, a detailed introduction to the steps and key points of LE-ULBD is provided. Simultaneously, a retrospective review of 132 consecutive patients who underwent LE-ULBD for central canal and/or lateral recess stenosis was conducted. The outcomes after more than two years of follow-up were assessed using the visual analogue score (VAS), Oswestry Disability Index (ODI), Japanese Orthopaedic Association (JOA) scores, and the modified MacNab criteria to evaluate surgical efficacy. All 132 patients underwent LE-ULBD successfully. Among them, 119 patients were rated as "excellent," while 13 patients were rated as "good" based on the modified MacNab criteria during the last follow-up. Incidental dural tears occurred in four cases, but there were no post-operative epidural hematomas or infections. The experience demonstrates that LE-ULBD is a less invasive, effective, and safe approach. It can be considered as an alternative option for treating patients with lumbar central canal stenosis and/or lateral recess stenosis.

Bivalves are a high-quality source of animal protein for human consumption. In recent years, the demand for bivalve proteins has increased dramatically, leading to a sharp increase in global production of marine bivalves. To date, although the amino acid profiles of many bivalves have been reported, such information has not been well organized. Therefore, there is an urgent need for a comprehensive scientific review of the protein quality of bivalves, especially commercially important edible bivalves. In this context, this study was conducted to evaluate the protein quality of commercially important edible bivalves. In general, most bivalves are rich in protein (> 50% of their dry weight) and amino acids (> 30 g/100g protein). Although most species of bivalves are rich in essential amino acids (EAA) (up to 50 g/100g protein), some species of edible bivalves have very low levels of EAA (< 5 g/100g protein). Based on the AA score, almost all bivalves have at least two limiting AAs. Most bivalve proteins provides delicious flavors with unami, sweetness and a hint of bitterness. The findings of this study not only serve as a a guide for selecting appropriate bivalves based on consumer preferences for specific AAs or AA scores, but also provide information on potential bivalve species for aquaculture to produce higher protein quality to meet the growing demand for high quality animal protein.

Auditory dysfunction and increased neuronal activity in the auditory pathways have been reported in patients with temporal lobe epilepsy, but the cellular mechanisms involved are unknown. Here, we report that microglia play a role in the disinhibition of auditory pathways after status epilepticus in mice. We found that neuronal activity in the auditory pathways, including the primary auditory cortex and the medial geniculate body (MGB), was increased and auditory discrimination was impaired after status epilepticus. We further demonstrated that microglia reduced inhibitory synapses on MGB relay neurons over an 8-week period after status epilepticus, resulting in auditory pathway hyperactivity. In addition, we found that local removal of microglia from the MGB attenuated the increase in c-Fos + relay neurons and improved auditory discrimination. These findings reveal that thalamic microglia are involved in auditory dysfunction in epilepsy., (© 2023 The Authors. GLIA published by Wiley Periodicals LLC.)

Monocyte aberrations have been increasingly recognized as contributors to renal damage in systemic lupus erythematosus (SLE), however, recognition of the underlying mechanisms and modulating strategies is at an early stage. Our studies have demonstrated that brain-derived neurotrophic factor precursor (proBDNF) drives the progress of SLE by perturbing antibody-secreting B cells, and proBDNF facilitates pro-inflammatory responses in monocytes. By utilizing peripheral blood from patients with SLE, GEO database and spontaneous MRL/lpr lupus mice, we demonstrated in the present study that CX3CR1 + patrolling monocytes (PMo) numbers were decreased in SLE. ProBDNF was specifically expressed in CX3CR1 + PMo and was closely correlated with disease activity and the degree of renal injury in SLE patients. In MRL/lpr mice, elevated proBDNF was found in circulating PMo and the kidney, and blockade of proBDNF restored the balance of circulating and kidney-infiltrating PMo. This blockade also led to the reversal of pro-inflammatory responses in monocytes and a noticeable improvement in renal damage in lupus mice. Overall, the results indicate that the upregulation of proBDNF in PMo plays a crucial role in their infiltration into the kidney, thereby contributing to nephritis in SLE. Targeting of proBDNF offers a potential therapeutic role in modulating monocyte-driven renal damage in SLE., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The incidence of prostate cancer (PCa), the most prevalent malignancy, is currently at the forefront. RNA modification is a subfield of the booming field of epigenetics. To date, more than 170 types of RNA modifications have been described, and N6-methyladenosine (m6A) is the most abundant and well-characterized internal modification of mRNAs involved in various aspects of cancer progression. METTL3, the first identified key methyltransferase, regulates human mRNA and non-coding RNA expression in an m6A-dependent manner. This review elucidates the biological function and role of METTL3 in PCa and discusses the implications of METTL3 as a potential therapeutic target for future research directions and clinical applications., (© 2023. The Author(s).)

Background: Endothelial barrier dysfunction is critical for the pathogenesis of sepsis-induced acute lung injury (ALI). Lipopolysaccharide (LPS)-stimulated human pulmonary microvascular endothelial cells (HPMECs) are widely used as the cell model of sepsis-associated ALI for exploration of endothelial barrier dysfunction. Dickkopf (DKK) family proteins were reported to mediate endothelial functions in various diseases. The present study explored the effect of Dickkopf-3 (DKK3) on endothelial barrier permeability, angiogenesis, and tight junctions in LPS-stimulated HPMECs., Methods: RT-qPCR was required for detecting DKK3 and miR-98-3p expression. The angiogenesis of HPMECs was evaluated by tube formation assays. Monolayer permeability of HPMECs was examined by Transwell rhodamine assays. The protein expression of DKK3 and tight junctions in HPMECs was measured via western blotting. Luciferase reporter assay was used to verify the interaction between miR-98-3p and DKK3., Results: LPS treatment inhibited angiogenetic ability while increasing the permeability of HPMECs. DKK3 expression was upregulated while miR-98-3p level was reduced in LPS-treated HPMECs. DKK3 knockdown alleviated HPMEC injury triggered by LPS stimulation. MiR-98-3p targeted DKK3 in HPMECs. Overexpression of miR-98-3p protects HPMECs from the LPS-induced endothelial barrier dysfunction, and the protective effect was reversed by DKK3 overexpression., Conclusions: MiR-98-3p ameliorates LPS-evoked pulmonary microvascular endothelial barrier dysfunction in sepsis-associated ALI by targeting DKK3.

RNA modification is a post-transcriptional level of regulation that is widely distributed in all types of RNAs, including mRNA, tRNA, rRNA, miRNA, and lncRNA, where N6-methyladenine (m 6 A) is the most abundant mRNA methylation modification. Significant evidence has depicted that m 6 A modifications are closely related to human diseases, especially cancer, and play pivotal roles in RNA transcription, splicing, stabilization, and translation processes. The most common urological cancers include prostate, bladder, kidney, and testicular cancers, accounting for a certain proportion of human cancers, with an ever-increasing incidence and mortality. The recurrence, systemic metastasis, poor prognosis, and drug resistance of urologic tumors have prompted the identification of new therapeutic targets and mechanisms. Research on m 6 A modifications may provide new solutions to the current puzzles. In this review, we provide a comprehensive overview of the key roles played by RNA modifications, especially m 6 A modifications, in urologic cancers, as well as recent research advances in diagnostics and molecularly targeted therapies., (© 2023. The Author(s).)

Purpose: The biomechanical capacity of "Barrel Hoop Plate (BHP)" in the treatment of the posterolateral tibial plateau (PL) depression fractures remains unknown. In this study, two kinds of posterolateral tibial plateau depression models involving mild slope-type depression fracture (MSDF) and local sink hole-type depression fracture (LSDF) were created to test and compare the biomechanical capacities of BHP with the other two conventional fixations (Anterolateral Plate and Posterolateral Plate, ALP and PLP) by finite element analysis., Methods: The 3D models of three kinds of plate-screw systems and the two kinds of PL-depression models (MSDF and LSDF) were created. An axial force of 400N was applied from the distal femur to the tibial plateau. The maximal displacements of the posterolateral fractures (PLFs), the distribution on the PLFs articular surface and key points displacements were measured. Stresses in the fixation complex including the maximal Equivalent (von-Mises) Stress of implants, the max shear stress of PLFs and stiffness of the fixation were calculated., Results: The maximal displacement of MSDF was least in Group BHP. The maximal displacement of LSDF was least in Group ALP. In MSDF, BHP showed the best rim fix effect in MSDF, but unsatisfactory results in LSDF. In both MSDF and LSDF, the greatest max Equivalent Stress of the plate and the screw occurred in the PLP system. ALP and BHP showed a comparable stiffness in MSDF and ALP had the strongest stiffness in the fixation of LSDF., Conclusions: In MSDF, the BHP has the best biomechanical capacity, especially in displacements of key points such as the PL rim, fracture line, and depression center. In LSDF, the ALP system shows the best biomechanical effect. Although the PLP has the best fixation effect on the posterior wall, it is not suitable for PL-depression fracture fixation., (© 2023. The Author(s).)

Ferroptosis has emerged as a promising target for anticancer treatment, comprising iron-dependent lipid peroxidation and excessive accumulation of reactive oxygen species. Given that glutathione (GSH) overproduced in tumor cells antagonizes the cellular oxidation system, the reduction of GSH production has been extensively explored to induce ferroptosis. However, reducing GSH production alone is insufficient to trigger an intense lipid peroxidation storm. It is highly desirable to achieve systemic GSH depletion through simultaneous production and consumption intervention. Herein, we propose a bidirectional blockage strategy for closed-loop GSH depletion-amplified tumor ferroptosis. Sorafenib (Sor) and gambogic acid (GA) were elaborately fabricated as a self-engineered carrier-free nanoassembly without any nanocarrier materials. The PEGylated dual-drug nanoassembly enables favorable co-delivery and tumor-specific release of Sor and GA. Notably, a closed-loop GSH depletion is observed as a result of a Sor-induced decrease in GSH production and GA-accelerated GSH consumption in vitro and in vivo . As expected, this uniquely engineered dual-drug nanoassembly demonstrates vigorous antitumor activity in 4T1 breast tumor-bearing mice. This study presents a novel nanotherapeutic modality for ferroptosis-driven cancer treatment.

Purpose: The prognosis of early-stage hepatocellular carcinoma (HCC) patients after radical resection has received widespread attention, but reliable prediction methods are lacking. Radiomics derived from enhanced computed tomography (CT) imaging offers a potential avenue for practical prognostication in HCC patients., Methods: We recruited early-stage HCC patients undergoing radical resection. Statistical analyses were performed to identify clinicopathological and radiomic features linked to recurrence. Clinical, radiomic, and combined models (incorporating clinicopathological and radiomic features) were built using four algorithms. The performance of these models was scrutinized via fivefold cross-validation, with evaluation metrics including the area under the curve (AUC), accuracy (ACC), sensitivity (SEN), and specificity (SPE) being calculated and compared. Ultimately, an integrated nomogram was devised by combining independent clinicopathological predictors with the Radscore., Results: From January 2016 through December 2020, HCC recurrence was observed in 167 cases (64.5%), with a median time to recurrence of 26.7 months following initial resection. Combined models outperformed those solely relying on clinicopathological or radiomic features. Notably, among the combined models, those employing support vector machine (SVM) algorithms exhibited the most promising predictive outcomes (AUC: 0.840 (95% Confidence interval (CI): [0.696, 0.984]), ACC: 0.805, SEN: 0.849, SPE: 0.733). Hepatitis B infection, tumour size > 5 cm, and alpha-fetoprotein (AFP) > 400 ng/mL were identified as independent recurrence predictors and were subsequently amalgamated with the Radscore to create a visually intuitive nomogram, delivering robust and reliable predictive performance., Conclusion: Machine learning models amalgamating clinicopathological and radiomic features provide a valuable tool for clinicians to predict postoperative HCC recurrence, thereby informing early preventative strategies., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Spinal cord stimulation is a technique in which different types of electrodes are placed in the spinal epidural space for neuromodulation. Surgical paddle electrodes (SEs) are usually implanted by a surgeon by performing open surgery with laminectomy. Recent advances in endoscopic spine surgery provide another option for minimally invasive SE implantation., Objectives: This anatomical study aims to examine the feasibility of implanting SEs in thoracic and cervical spine segments, discussing the specific advantages and disadvantages compared with previously reported methods., Study Design: Laboratory study with Institutional Review Board No B2023-056., Methods: Four fresh adult cadavers (2 women, 2 men) were operated on in this study. The posterior unilateral biportal endoscopic surgical approach, the accessibility to the intraspinal epidural space, and the technical possibilities and limitations of implantation of SEs were evaluated, as well as the surgical duration and complications., Results: All the planned steps of the operation were successfully accomplished in all 4 cadavers. A total of 8 electrodes were successfully implanted through the working portal. Among them, 4 were located in the cervical segment and 4 in the thoracic segment. The proper position of the electrodes was also verified by fluoroscopy. No rupture of dura occurred during the operation. Except for the first cadaver, the duration of surgery did not exceed 1 hour., Limitations: Anatomical study on human cadavers, the quantity of cadavers, and the steep learning curve., Conclusions: The results of this anatomical study show that the SEs can be satisfactorily implanted in cervical and thoracic segments using the unilateral biportal endoscopic technique.

Nitric oxide (NO) is a gaseous molecule endowed with diverse biological functions, offering vast potential in the realm of cancer treatment. Considerable efforts have been dedicated to NO-based cancer therapy owing to its good biosafety and high antitumor activity, as well as its efficient synergistic therapy with other antitumor modalities. However, delivering this gaseous molecule effectively into tumor tissues poses a significant challenge. To this end, nano drug delivery systems (nano-DDSs) have emerged as promising platforms for in vivo efficient NO delivery, with remarkable achievements in recent years. This review aims to provide a summary of the emerging NO-driven antitumor nanotherapeutics. Firstly, the antitumor mechanism and related clinical trials of NO therapy are detailed. Secondly, the latest research developments in the stimulation of endogenous NO synthesis are presented, including the regulation of nitric oxide synthases (NOS) and activation of endogenous NO precursors. Moreover, the emerging nanotherapeutics that rely on tumor-specific delivery of NO donors are outlined. Additionally, NO-driven combined nanotherapeutics for multimodal cancer theranostics are discussed. Finally, the future directions, application prospects, and challenges of NO-driven nanotherapeutics in clinical translation are highlighted., (Copyright © 2023 Elsevier B.V. All rights reserved.)

CONSTANS (CO) is the key gene in the photoperiodic pathway that regulates flowering in plants. In this paper, a CONSTANS-like 14A (COL14A) gene was obtained from mango, and its expression patterns and functions were characterized. Sequence analysis shows that MiCOL14A-JH has an additional A base, which leads to code shifting in subsequent coding boxes and loss of the CCT domain. The MiCOL14A-JH and MiCOL14A-GQ genes both belonged to group Ⅲ of the CO/COL gene family. Analysis of tissue expression patterns showed that MiCOL14A was expressed in all tissues, with the highest expression in the leaves of seedling, followed by lower expression levels in the flowers and stems of adult leaves. However, there was no significant difference between different mango varieties. At different development stages of flowering, the expression level of MiCOL14A-GQ was the highest in the leaves before floral induction period, and the lowest at flowering stage, while the highest expression level of MiCOL14A-JH appeared in the leaves at flowering stage. The transgenic functional analysis showed that both MiCOL14A-GQ and MiCOL14A-JH induced delayed flowering of transgenic Arabidopsis. In addition, MiCOL14A-JH enhanced the resistance of transgenic Arabidopsis to drought stress, while MiCOL14A-GQ increased the sensitivity of transgenic Arabidopsis to salt stress. Further proteinprotein interaction analysis showed that MiCOL14A-JH directly interacted with MYB30-INTERACTING E3 LIGASE 1 (MiMIEL1), CBL-interacting protein kinase 9 (MiCIPK9) and zinc-finger protein 4 (MiZFP4), but MiCOL14A-GQ could not interact with these three stress-related proteins. Together, our results demonstrated that MiCOL14A-JH and MiCOL14A-GQ not only regulate flowering but also play a role in the abiotic stress response in mango, and the lack of the CCT domain affects the proteinprotein interaction, thus affecting the gene response to stress. The insertion of an A base can provide a possible detection site for mango resistance breeding., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Immune checkpoint inhibitor (ICI) treatments are promising therapies for hepatocellular carcinoma (HCC) patients. However, not all HCC patients benefit from immunotherapy. Therefore, it is urgent to explore markers for the clinical efficacy and prognosis of immunotherapy for liver cancer. This study aimed to investigate changes in peripheral blood lymphocyte subsets after immunotherapy and to assess their predictive and prognostic value. Methods: Sixty-one patients with advanced HCC were enrolled. Peripheral blood samples were collected from HCC patients before and after ICI treatment, and lymphocytes were detected by flow cytometry. The rank sum test, chi-square test, Kaplan‒Meier curve, and Cox regression model were used to determine the relationship between the changes in the percentages of peripheral blood lymphocyte subsets and clinicopathological characteristics, clinical efficacy, progression-free survival (PFS) and overall survival (OS). Results: After ICI treatment, the percentage of CD3 + CD8 + T cells increased, and the percentage of B cells decreased. The changes in memory T cells percentages varied according to different immune efficacy groups. Age, history of hepatitis B infection, first-line therapy, and distant metastasis influenced the proportion of peripheral blood lymphocyte subsets in patients with advanced HCC. Furthermore, univariate analysis demonstrated that high percentage changes in the natural killer (NK) cells percentage change predicted longer PFS and OS. Conclusions: ICI treatment alters the percentage of peripheral blood lymphocyte subsets in immunotherapy-treated HCC patients. Changes in the proportion of lymphocyte subsets are influenced by variances in immunological response and clinicopathological features. A high degree of NK cells percentage change in HCC patients treated with ICI represents an independent prognostic predictor., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Urological tumors, such as prostate cancer, renal cell carcinoma, and bladder cancer, have shown a significant rise in prevalence in recent years and account for a significant proportion of malignant tumors. It has been established that metastasis to distant organs caused by urological tumors is the main cause of death, although the mechanisms underlying metastasis have not been fully elucidated. The fibronectin receptor integrin α5β1 reportedly plays an important role in distant metastasis and is closely related to tumor development. It is widely thought to be an important cancer mediator by interacting with different ligands, mediating tumor adhesion, invasion, and migration, and leading to immune escape. In this paper, we expound on the relationship and regulatory mechanisms of integrin α5β1 in these three cancers. In addition, the clinical applications of integrin α5β1 in these cancers, especially against treatment resistance, are discussed. Last but not least, the possibility of integrin α5β1 as a potential target for treatment is examined, with new ideas for future research being proposed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhou, Zhu, Luo, Xiao, Zou, Zou and Zhang.)