Search

Bei Li,1,2,* Yuting Luo,1,2,* Geng Liu,1,2 Maling Gou,3 Lei Feng,1,2 Xiwen Ye,1,2 Jianrong Xu,1,2 Yaotian Fan,1,2 Zhen You1,2 1Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 2Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 3Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhen You, Tel/Fax +86 028 85423823, Email youzhen@wchscu.cnIntroduction: Hepatocellular carcinomas (HCC) have a high morbidity and mortality rate, and is difficult to cure and prone to recurrence when it has already developed. Therefore, early detection and efficient treatment of HCC is necessary.Methods: In this study, we synthesized a novel NDI polymer with uniform size, long-term stability, and high near-infrared two-zone (NIR-II) absorption efficiency, which can greatly enhance the effect of photothermal therapy (PTT) after intravenous injection into Huh-7-tumor bearing mice.Results: The in vitro and in vivo studies showed that NDI polymer exhibited excellent NIR-guided PTT treatment, and the antitumor effect was approximately 88.5%, with obvious antimetastatic effects.Conclusion: This study developed an NDI polymer-mediated integrated diagnostic and therapeutic modality for NIR-II fluorescence imaging and photothermal therapy.Keywords: hepatocellular carcinoma, photothermal therapy, NDI polymer, NIR-II imaging

Jinlu Liu,1,* Ling Yang,1,* Xin Yuan,2,* Meimei Xiong,1 Jiao Zhu,1 Wenbi Wu,1 Min Ren,1 Jianlin Long,3 Xuewen Xu,2 Maling Gou1 1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Plastic and Burn Surgery, West China Hospital of Sichuan University, Chengdu, 610041, People’s Republic of China; 3Department of Medical Oncology, Chongqing University Cancer Hospital, Chongqing, 400030, People’s Republic of China*These authors contributed equally to this workCorrespondence: Maling GouState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of ChinaEmail goumaling@scu.edu.cnXuewen XuDepartment of Plastic and Burn Surgery, West China Hospital of Sichuan University, Chengdu, 610041, People’s Republic of ChinaEmail xxw_0826@163.comIntroduction: β-lactamase (LACTB) is a tumor suppressor gene in various tumors including melanoma. However, it remains challenging to efficiently deliver the LACTB gene into melanoma. Recently, we designed a nonviral nanocarrier iRGD/DOTAP/MPEG-PDLLA (iDPP) that could deliver gene targetedly to melanoma efficiently without obvious adverse effects.Methods: In this study, the tumor-targeted nanoparticle iDPP was prepared to deliver LACTB gene to treat melanoma in vitro and in vivo. First, the expression level of LACTB in 6 clinical specimens of melanoma patients was evaluated. Subsequently, the characteristics of iDPP/LACTB nanocomplexes were studied. Afterwards, the in vitro and in vivo anti-tumor efficacy of the iDPP/LACTB nanocomplexes were explored utilizing the B16-F10 mouse melanoma cell line and the B16-F10 subcutaneous melanoma model.Results: Compared with the normal epithelium, the expression level of LACTB in melanoma tissues was significantly downregulated. In vitro B16-F10 cell tests showed iDPP/LACTB nanocomplexes could increase the mRNA levels of P21, Bid, Bax, Pidd1, and Sival genes and up-regulate the p53 signaling pathway of melanoma cells, thus promoting cell apoptosis and blocking the cell cycle. Injected intravenously, iDPP nanoparticles could deliver DNA to the subcutaneous melanoma targetedly. Based on in vivo mouse xenograft model, iDPP/LACTB nanocomplexes could effectively inhibit tumor proliferation and induce tumor apoptosis, thus significantly inhibiting melanoma growth (tumor inhibition rate is about 68%) in the subcutaneous B16-F10 melanoma model.Conclusion: The downregulated LACTB might be a potential target for melanoma therapy. The iDPP/LACTB nanocomplexes could inhibit the growth of the mouse melanoma without obvious side effects, which provide a new option for melanoma gene therapy research.Keywords: melanoma, LACTB, nanocomplexes, gene therapy

Min Sui,1,* Meimei Xiong,2,* Yuling Li,1,* Qiao Zhou,1 Xiaofei Shen,3 Da Jia,3 Maling Gou,2 Qingxiang Sun1 1Department of Pathology and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Centre for Biotherapy, Chengdu, 610041, People’s Republic of China; 2State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, People’s Republic of China; 3Key Laboratory of Birth Defects and Related Diseases of Women and Children, Department of Pediatrics, Division of Neurology, West China Second University Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qingxiang Sun; Maling Gou Email sunqingxiang@hotmail.com; goumaling@scu.edu.cnIntroduction: Peptides can be rationally designed as non-covalent inhibitors for molecularly targeted therapy. However, it remains challenging to efficiently deliver the peptides into the targeted cells, which often severely affects their therapeutic efficiency.Methods: Herein, we created a novel non-covalent peptide inhibitor against nuclear export factor CRM1 by a structure-guided drug design method and targetedly delivered the peptide into cancer cells by a nanoparticle-mediated gene expression system for use as a cancer therapy.Results: The nuclear export signal (NES)-optimized CRM1 peptide inhibitor colocalized with CRM1 to the nuclear envelope and inhibited nuclear export in cancer cell lines in vitro. The crystal structures of the inhibitors complexed with CRM1 were solved. In contrast to the covalent inhibitors, the peptides were similarly effective against cells harboring the CRM1 C528S mutation. Moreover, a plasmid encoding the peptides was delivered by a iRGD-modified nanoparticle to efficiently target and transfect the cancer cells in vivo after intravenous administration. The peptides could be selectively expressed in the tumor, resulting in the efficient inhibition of subcutaneous melanoma xenografts without obvious systemic toxicity.Discussion: This work provides an effective strategy to design peptide-based molecularly targeted therapeutics, which could lead to the development of future targeted therapy.Keywords: CRM1, non-covalent inhibitor, crystal structures, DNA nanocomplex, protein engineering

Qianqian Zhang,1,2,* Meimei Xiong,2,* Jinlu Liu,1,2 Shuai Wang,2 Ting Du,2 Tianyi Kang,2 Yu Liu,2 Hao Cheng,2 Meijuan Huang,1 Maling Gou21Department of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China*These authors contributed equally to this workBackground: Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) is a novel tumor suppressor. However, whether LHPP is effective to melanoma has not been investigated. Gene therapy provides a new strategy for the treatment of melanoma. Currently, it suffers from the lack of safe and effective gene delivery systems. Methods: A CRGDKGPDC peptide (iRGD) modified hybrid monomethoxy poly(ethylene glycol)-poly(D,L-lactide) nanoparticle (iDPP) was prepared and complexed with a LHPP plasmid, forming an iDPP/LHPP nanocomplex. The iDPP/LHPP nanocomplex was characterized by particle size distribution, zeta potential, morphology, cytotoxicity, and transfection efficiency. The antitumor efficacy of the nanocomplex against melanoma was studied both in vitro and in vivo. Further, the potential epigenetic changes in melanoma induced by iDPP/LHPP nanocomplex were evaluated.Results: The iDPP/LHPP nanocomplex showed high transfection efficiency and low toxicity. Moreover, the nanocomplex displayed a neutral charge that can meet the requirement of intravenous injection for targeted gene therapy. In vitro and in vivo experiments indicated that the iDPP/LHPP nanocomplex significantly inhibited the melanoma growth without causing notable adverse effects. We also found that LHPP played an important role in epigenetics. It regulated the expression of genes related to the proliferation and apoptosis chiefly at the level of transcription.Conclusion: This work demonstrates that the iDPP nanoparticle-delivered LHPP gene has a potential application in melanoma therapy through regulation of the genes associated with epigenetics.Keywords: melanoma, LHPP, nanoparticle, gene therapy, epigenetics

Tianyi Kang,1 Chenyang Li,1,2 Ting Du,1 Yujiao Wu,1 Yuping Yang,1 Xuan Liu,1 Qianqian Zhang,1 Xiaoping Xu,3 Maling Gou1,4 1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China; 2Shanghai Institutes for Biological Science, Chinese Academy of Science, Shanghai 200031, People’s Republic of China; 3West China School of Pharmacy, Sichuan University, Chengdu 610041, People’s Republic of China; 4Co-Innovation Center for Micro/Nano Optoelectronic Materials and Devices, Chongqing 402160, People’s Republic of China Background: Melittin, the main active peptide ingredient of bee venom, can cause severe cell membrane lysis due to its robust interaction with negatively charged phospholipids. So far, no effective anti-melittin vaccine has been developed to protect people from undesired melittin intoxication.Methods: Herein, we prepared a polydiacetylene (PDA) nanoparticle with cell membrane-mimic surface to complex melittin, forming an anti-melittin vaccine (PDA–melittin).Results: PDA nanoparticles could effectively combine with melittin and neutralize its toxicity. PDA–melittin nanocomplex is demonstrated to enhance melittin uptake by DCs and stimulate strong melittin-specific immunity. Mice immunized with PDA–melittin nanocomplex showed higher survival rate after exposion to melittin than untreated mice.Conclusion: The PDA–melittin nanocomplex can efficiently and safely generate a specific immunity against melittin to protect body from melittin intoxication, providing a new method with potential clinical application for the treatment of melittin intoxication.Keywords: PDA nanoparticles, melittin, toxoid vaccine, immunity

Luo L, Du T, Zhang J, et al. Int J Nanomedicine. 2016;11:501—513. The authors have advised due to an error at the time of figure assembly, Figure 11 on page 510 is incorrect. The correct Figure 11 is shown below. The authors apologize for this error and advise it does not affect the results of the paper. Read the original article

Xun Jin,1 Peilan Zhang,1 Li Luo,1 Hao Cheng,1 Yunzu Li,1 Ting Du,1 Bingwen Zou,2 Maling Gou1 1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, People’s Republic of China; 2Department of Thoracic Oncology, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, People’s Republic of China Abstract: Nanoparticles have promising applications in drug delivery for cancer therapy. Herein, we prepared cationic 1,2-dioleoyl-3-trimethylammonium propane/methoxypoly (ethyleneglycol) (DPP) nanoparticles to deliver doxorubicin (Dox) for intravesical therapy of bladder cancer. The DPP micelles have a mean dynamic diameter of 18.65 nm and a mean zeta potential of +19.6 mV. The DPP micelles could prolong the residence of Dox in the bladder, enhance the penetration of Dox into the bladder wall, and improve cellular uptake of Dox. The encapsulation by DPP micelles significantly improved the anticancer effect of Dox against orthotopic bladder cancer in vivo. This work described a Dox-loaded DPP nanoparticle with potential applications in intravesical therapy of bladder cancer. Keywords: bladder cancer, drug delivery, nanoparticles, intravesical therapy

Xun Jin,1,* Bingwen Zou,2,* Li Luo,1,* Chuanhong Zhong,3 Peilan Zhang,1 Hao Cheng,1 Yanfang Guo,1 Maling Gou1 1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, 2Department of Thoracic Oncology, Cancer Center, West China Hospital, Medical School, Sichuan University, Chengdu, 3Department of Neurosurgery, The Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan Province, People’s Republic of China *These authors contributed equally to this work Abstract: Cancer chemotherapy can benefit from the combination of different anticancer drugs. Here, we prepared doxorubicin (Dox)- and thioridazine (Thio)-coloaded methoxy poly(ethylene glycol)-poly(L-lactic acid) (MPEG-PLA) nanoparticles (NPs) for breast cancer therapy. These NPs have an average particle size of 27 nm. The drug loading efficiencies of Thio and Dox are 4.71% and 1.98%, respectively. Compared to the treatment of Thio or Dox alone, the combination of Thio and Dox exhibited a synergistic effect in inhibiting the growth of 4T1 breast cancer cells in vitro. In addition, the Thio- and Dox-coloaded MPEG-PLA NPs could efficiently suppress the growth of breast cancer cells in vivo. This study suggests that Thio- and Dox-coloaded MPEG-PLA NPs might have potential applications in breast cancer treatment. Keywords: thioridazine, doxorubicin, codelivery, nanoparticles, breast cancer

Li Luo,1,* Ting Du,1,* Jiumeng Zhang,1 Wei Zhao,2 Hao Cheng,1 Yuping Yang,1 Yujiao Wu,1 Chunmei Wang,1 Ke Men,1 Maling Gou1 1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, 2Department of Thoracic Oncology, Cancer Center, West China Hospital, Medical School, Sichuan University, Chengdu, People’s Republic of China *These authors contributed equally to this work Abstract: Gene therapy has promising applications in ovarian cancer therapy. Blocking the function of the survivin protein could lead to the growth inhibition of cancer cells. Herein, we used degradable heparin–polyethyleneimine (HPEI) nanoparticles to deliver a dominant-negative human survivin T34A (hs-T34A) gene to treat ovarian cancer. HPEI nanoparticles were characterized and were found to have a dynamic diameter of 66±4.5 nm and a zeta potential of 27.1±1.87 mV. The constructed hs-T34A gene expression plasmid could be effectively delivered into SKOV3 ovarian carcinoma cells by HPEI nanoparticles with low cytotoxicity. Intraperitoneal administration of HPEI/hs-T34A complexes could markedly inhibit tumor growth in a mouse xenograft model of SKOV3 human ovarian cancer. Moreover, according to our results, apparent apoptosis of cancer cells was observed both in vitro and in vivo. Taken together, the prepared HPEI/hs-T34A formulation showed potential applications in ovarian cancer gene therapy. Keywords: human survivin T34A, heparin–polyethyleneimine nanoparticles, gene therapy, ovarian cancer

Abstract Lysyl oxidase-like 2 (LOXL2) mediates the crosslinking of extracellular collagen, reflecting qualitative changes in liver fibrosis. This study aimed to validate the utility of serum LOXL2 levels as a predictive biomarker for the development of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) infection who achieved a sustained virological response (SVR). This retrospective study included 137 patients with chronic HCV infection without history of HCC development and who achieved SVR via direct-acting antiviral therapy. Median LOXL2 levels decreased significantly after SVR achievement (pre-Tx, 2.33 ng/mL; post-Tx, 1.31 ng/mL, p

The aim of the present work was to evaluate the effect of reducing nitrite content on the physicochemical, microbiological, proteolytic, and volatile properties of Cantonese sausages during fermentation and storage. The Cantonese sausages were divided into six groups based on the amount of nitrite added (0, 30, 60, 90, 120, and 150 mg/kg). Results showed that among the physicochemical parameters, moisture, weight loss, a* value, thiobarbituric acid reactive substance value, and nitrite residue levels were significantly affected (p < 0.05) along with nitrite reduction. In addition, the total viable counts and Gram-positive cocci increased with the reduction of nitrite, while lactic acid bacteria decreased. The band densities of actin (48 kDa) increased with the reduction of nitrite, while no major change in sarcoplasmic protein bands was observed. The results of volatile compounds suggested that the reduction of nitrite mainly affected compounds originating from carbohydrate fermentation, esterase activity, and lipid oxidation. [ABSTRACT FROM AUTHOR]

Abstract Recent spread of the COVID-19 forces governments around the world to temporarily close educational institutions. In this paper, we evaluated learning engagement, level of satisfaction and anxiety of e-book based remote teaching strategy on an online learning platform. The research involves 358 students at an urban junior-high school in Japan. Learning logs were analyzed to measure student engagement, whereas survey responses indicated their perception regarding the remote learning experience. Log analysis revealed that the average completion rate over 267 learning materials was 67%. We also observed a significant decrease in engagement 3 weeks after remote learning and different subjects and grades. Survey analysis showed students felt both satisfaction and anxiety about remote learning. However, there were significant differences in the level of satisfaction between different grades. The results indicated that (1) maintaining students’ motivation is a challenge to remote learning in secondary schools, and (2) we need to relieve students’ anxiety about their own progress in the class and their classes after the break. This study is the first to report trends in actual teaching–learning engagement, which were recorded during sessions of emergency remote teaching in Japanese schools. The results can inform the future implementation of remote learning in junior-high schools.

Aiming at the problem that the traditional steganography based on carrier modification has the low steganographic capacity, a steganographic scheme based on Fully Convolutional Dense Connection Network (FC-DenseNet) is proposed. Since FC-DenseNet can effectively overcome the problems of gradient dissipation and gradient explosion, and a large number of features are multiplexed, the cascaded secret image and carrier image can reconstruct good image quality after entering the network. Effectively improve steganographic capacity. First, we reset the number of input channels of the first convolution block of FC-DenseNet and the number of output channels of the last convolution block and deleted the LogSoftmax() function. On the sender side, after the concatenated secret image and carrier image pass through the hidden network FC-DenseNet, the secret image is embedded in the carrier image to obtain a stego-image. At the receiving side, the extraction network reconstructs the secret image from the stego-image. Experimental results show that our proposed steganography scheme not only has a high Peak Signal-to-Noise Ratio(PSNR) and Structural Similarity(SSIM) but also can realize large-capacity image steganography, with an average image payload capacity of 23.96 bit per pixel.

One of the advantages of cement and the cement concrete industry in sustainability is the ability to utilize large amounts of industrial solid wastes such as fly ash and ground granulated blast furnace slag. Tailings are solid wastes of the ore beneficiation process in the extractive industry and are available in huge amounts in some countries. This paper reviews the potential utilization of tailings as a replacement for fine aggregates, as supplementary cementitious materials (SCMs) in mortar or concrete, and in the production of cement clinker. It was shown in previous research that while tailings had been used as a replacement for both fine aggregate and cement, the workability of mortar or concrete reduced. Also, at a constant water to cement ratio, the compressive strength of concrete increased with the tailings as fine aggregate. However, the compressive strength of concrete decreased as the replacement content of the tailings as SCMs increased, even whentailings were ground into smaller particles. Not much research has been dedicated to the durability of concrete with tailings, but it is beneficial for heavy metals in tailings to stabilize/solidify in concrete. The clinker can be produced by using the tailings, even if the tailings have a low SiO2 content. As a result, the utilization of tailings in cement and concrete will be good for the environment both in the solid waste processing and virgin materials using in the construction industry.

Background: The survival benefit from later-line treatment for patients with metastatic colorectal cancer (mCRC) remains disappointing. Here, in a real-world study, we were aimed to evaluate which choice will affect the survival of mCRC patients after standard treatment in Chinese patients., Methods: A total of 129 patients with refractory mCRC were involved in the study. They received targeted monotherapy or combined with chemo-agents or PD-1 inhibitor before death. Overall survival (OS) and progression-free survival (PFS) were reviewed and evaluated from clinical features and treatment options., Results: Among the 129 patients, the median age was 56 years (25-81). The mOS from third-line was 12.5 months. OS of patients who treated with chemo plus targeted therapy group in third-line was shown to be superior to pd-1 inhibitor in combination with antiangiogenic agents or antiangiogenic monotherapy group (15.6 m vs. 10.5 m vs. 8.4 m, p < 0.05). Patients had received triplet-drugs (bevacizumab plus low-dose irinotecan and oxaliplatin) and had prolonged survival compared to those had not (21.3 m vs 10.3 m, p = 0.004). OS between patients who had immunotherapy history or not was not significantly different (p > 0.05). The mPFS was 3.5 months in patients who had administered with antiangiogenic targeted agents plus anti-pd-1 and 4.7 months in chemo plus targeted therapy group and 2.2 months in the other group. In the triplet drugs group, preliminary results showed that ORR was 13.3% and DCR was 80%. The median PFS was 5.1 m, and the median OS was 10.6 m., Conclusions: Triplet drugs resulted in significantly longer overall survival, and immunotherapy may have limited benefit in MSS type CRC patients., Competing Interests: Declarations Consent for Publication All the authors had consent for publication. Ethics Approval and Consent to Participate This retrospective study was approved by the independent ethics committee of the Chinese PLA General Hospital and performed in accordance with the Declaration of Helsinki, and all the authors obtained written informed consent from the participants, to participate in the study. Competing Interests The authors declare no competing interests., (© 2024. The Author(s).)

Anaerobic digestion (AD) frequently encounters disturbances due to variations in organic loading rates (OLRs), which can result in the failure of the sludge treatment process. However, there is a lack of comprehensive studies on the robustness of AD systems against OLR disturbances and the underlying mechanisms. In this study, the responses of reactor performance and active microbial communities in mesophilic AD were investigated and compared under conditions of OLR shock and OLR fluctuation. Statistical analysis confirmed that all reactors recovered from both types of OLR disturbance, indicating both functional and structural robustness of the mesophilic community. Based on metagenomics and metatranscriptomics analyses, it was observed that high diversity within the microbial community led to functional redundancy, which appears to be a key mechanism contributing to the robustness against OLR disturbances. Additionally, for the first time, the potential metabolic diversity of aerobic autotrophy bacteria in AD reactors was identified, including their roles in the utilization of glucose and acetate. Furthermore, the analysis of topological properties within the microbial interaction network was conducted, and the robustness of the community network was verified through the application of random node deletion attacks. The findings from this study provide valuable information for the effective regulation of microbial communities and the design of practical AD systems., 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 Ltd. All rights reserved.)

Xanthan gum, produced by the aerobic fermentation of carbohydrates by Xanthomonas campestris, is a significant natural and industrial biopolymer known for its exceptional properties. Enhancing the yield of xanthan gum production remains a critical challenge. This study employed atmospheric and room temperature plasma (ARTP) technology to induce mutagenesis in X. campestris, resulting in a high-yielding strain, X20. The X20 mutant exhibited a substantial increase in xanthan gum yield, ranging from 13.3 % to 30.0 % over the starting strain across NaCl concentrations of 0, 6.0, and 8.0 g/L, along with improved viscosity and molecular weight. In the whole genome of X20 mutant, a total of 80 variant sites differing from the reference genome were identified, involving 76 mutated genes. Among these, 19 were missense mutations primarily associated with the two-component system. Transcriptome analysis highlighted their role in enhancing flagellar movement, biofilm formation, and metabolic synthesis, thereby elevating the capability of the mutant strain in xanthan gum production. This study demonstrates the potential of ARTP as an effective tool for microbial mutagenesis breeding, providing theoretical guidance for future studies on the synthesis regulation of xanthan gum and the engineering modification of X. campestris., 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.)

Transplantation of insulin-secreting cells provides a promising method for re-establishing the autonomous blood glucose control ability of type 1 diabetes (T1D) patients, but the low survival of the transplanted cells hinder the therapeutic efficacy. In this study, we 3D-printed an encapsulation system containing β-like cells and microvascular fragments (MVF), to create a retrivable microdevice with vascularized islets in vivo for T1D therapy. The functional β-like cells were differentiated from the urine epithelial cell-derived induced pluripotent stem cells (UiPSCs). Single-cell RNA sequencing provided an integrative study and macroscopic developmental analyses of the entire process of differentiation, which revealed the developmental trajectory of differentiation in vitro follows the developmental pattern of embryonic pancreas in vivo. The MVF were isolated from the epididymal fat pad. The microdevice with a groove structure were rapidly fabricated by the digital light processing (DLP)-3D printing technology. The β-like cells and MVF were uniformly distributed in the device. After subcutaneous transplantation into C57BL/6 mice, the microdevice have less collagen accumulation and low immune cell infiltration. Moreover, the microdevice encapsulated vascularized islets reduced hyperglycemia in 33 % of the treated mice for up to 100 days without immunosuppressants, and the humanized C-peptide was also detected in the serum of the mice. In summary, we described the microdevice-protected vascularized islets for long-term treatment of T1D, with high safety and potential clinical transformative value, and may therefore provide a translatable solution to advance the research progress of β cell replacement therapy for T1D., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The living tumor cell vaccine (TCV) holds a promise for cancer immunotherapy. Microneedle arrays provide a tool to improve the immune response of vaccines by the intradermal administration in a painless manner. However, it remains challenges for microneedle arrays to deliver the living TCV intradermally. Here, an ice microneedle array delivered living TCVs is shown with sustained granulocyte-macrophage colony-stimulating factor (GM-CSF) secretion for cancer treatment. The ice microneedle array is composed of ice microneedles and a matching polymer holder, which are customized fabricated by a static optical projection lithography (SOPL) technique. The living TCV consisted of irradiated melanoma cells transfected with nanoparticle-mediated GM-CSF plasmids. After the living TCV is readily loaded into the ice microneedle via a cryopreservation process, it could be efficiently delivered into the dermis by the microneedle device. Compared to the subcutaneous injection, intradermal administration led to the recruitment of more dendritic cells at the vaccination site and the increased infiltration of CD8 + T cells in the tumor. The ice microneedle array deliveres intradermal TCVs significantly inhibited melanoma growth and effectively prevented melanoma recurrence without obvious side effects. This work demonstrates a promising TCVs for melanoma treatment, which will inspire the future of cancer immunotherapy., (© 2024 Wiley‐VCH GmbH.)

Background: The role of HEPACAM family member 2 (HEPACAM2) is unclear in colorectal cancer (CRC)., Objective: The objective of this study was to perform an extensive examination of HEPACAM2 and validate it experimentally in CRC., Methods: This study investigated the significance of HEPACAM2 in CRC and its potential diagnostic utility utilizing data from the Cancer Genome Atlas (TCGA) database. Additionally, the study examined potential regulatory networks involving HEPACAM2, including its associations with immune infiltration, immune checkpoint genes, tumor mutational burden (TMB), microsatellite instability (MSI), mRNA expression-based stemness index (mRNAsi), and drug sensitivity in CRC. The expression of HEPACAM2 was further validated using the GSE89076 dataset, and quantitative reverse transcription PCR (qRT-PCR) was employed to confirm HEPACAM2 expression levels in six pairs of CRC tissue samples., Results: HEPACAM2 exhibited abnormal expression patterns in various types of cancer, including CRC. A decrease in HEPACAM2 expression levels in CRC was found to be significantly correlated with the T stage (p < 0.001). Reduced HEPACAM2 expression in CRC patients was also linked to poorer overall survival (OS) (p = 0.007). The expression levels of HEPACAM2 in CRC patients were identified as an independent prognostic factor (p = 0.016). Furthermore, HEPACAM2 was associated with TCF-dependent signaling in response to WNT, G2/M checkpoints, and other pathways. The expression of HEPACAM2 in CRC was found to be associated with immune infiltration, immune checkpoint genes, TMB / MSI, and mRNAsi. Additionally, the expression of HEPACAM2 in CRC was significantly and inversely correlated with the drug sensitivities to gw772405x and 6-phenyl-6h-indeno[1,2-c]isoquinoline-5,11-dione. qRT-PCR confirmed that the expression level of HEPACAM2 was found to be lowly expressed in CRC tissues., Conclusion: These findings suggest that HEPACAM2 may serve as a potential prognostic biomarker and immunotherapeutic target for CRC patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Haematological patients with severe thrombocytopenia and high thrombotic risk face challenges related to balancing bleeding and thrombosis risks. This study investigated factors associated with bleeding and thrombosis in high-risk haematological oncology patients with severe thrombocytopenia not receiving anticoagulant therapy and characterized their clinical features when both events occurred., Methods: A total of 446 haematological oncology patients with Caprini scores ≥ 5 were included from July 2022 to June 2023 at Mianyang City Central Hospital. Those not receiving prophylactic anticoagulants due to an admission platelet count < 50 × 10 9 /L were studied. Patients were categorized into bleeding/nonbleeding and thrombotic/nonthrombotic groups on the basis of hospital course. Relevant clinical data were collected, and univariate/multivariate logistic regression was used to analyse the influencing factors. The platelet count at admission was assessed via ROC curves for thrombosis prediction., Results: In the bleeding group, higher proportions of patients with leukaemia, myeloid tumours, lung infections, and a central venous catheter (CVC) with two lumens were observed, along with shorter catheter durations, lower initial and minimum platelet counts during hospitalization, and prolonged plasminogen times (all P < 0.05). The thrombotic group had a greater thrombosis history, initial platelet count, use of two venous catheter lumens, parenteral nutrition, sedation, and autologous haematopoietic stem cell transplantation (Auto-HSCT), with a lower leukaemia proportion (P < 0.05). Logistic regression identified lymphoma type and minimum platelet count as bleeding protective factors and the Charlson Comorbidity Index (CCI) score as an independent risk factor. Thrombosis history, two venous catheter lumens, and sedation were risk factors for thrombosis. The median platelet count was lower at bleeding and thrombosis than at admission (P = 0.007). The platelet count at admission had predictive value for thrombosis, especially severe thrombocytopenia, with an AUC of 0.735 (95% CI 0.613-0.858, P = 0.003) and a cut-off value of 42.5 × 10 9 /L., Conclusions: For haematological neoplasm patients with a high risk of venous thromboembolism (VTE), severe thrombocytopenia and high CCI scores, risk prevention and control of bleeding take precedence over thrombosis prophylaxis. Prophylactic anticoagulation is still recommended for patients with lymphoma assessed at high risk for VTE and with platelet counts of at least 42.5 × 10 9 /L., (© 2024. The Author(s).)

Disease resistance is often associated with compromised plant growth and yield due to defense-growth tradeoffs. However, key components and mechanisms underlying the defense-growth tradeoffs are rarely explored in maize. In this study, we find that ZmSKI3, a putative subunit of the SUPERKILLER (SKI) complex that mediates the 3'-5' degradation of RNA, regulates both plant development and disease resistance in maize. The Zmski3 mutants showed retarded plant growth and constitutively activated defense responses, while the ZmSKI3 overexpression lines are more susceptible to Curvularia lunata and Bipolaris maydis. Consistently, the expression of defense-related genes was generally up-regulated, while expressions of growth-related genes were mostly down-regulated in leaves of the Zmski3-1 mutant compared to that of wild type. In addition, 223 differentially expressed genes that are up-regulated in Zmski3-1 mutant but down-regulated in the ZmSKI3 overexpression line are identified as potential target genes of ZmSKI3. Moreover, small interfering RNAs targeting the transcripts of the defense- and growth-related genes are differentially accumulated, likely to combat the increase of defense-related transcripts but decrease of growth-related transcripts in Zmski3-1 mutant. Taken together, our study indicates that plant growth and immunity could be regulated by both ZmSKI3-mediated RNA decay and post-transcriptional gene silencing in maize., (© 2024 The Author(s). Journal of Integrative Plant Biology published by John Wiley & Sons Australia, Ltd on behalf of Institute of Botany, Chinese Academy of Sciences.)

As one of the two most ancient groups of extant vertebrates, lamprey has become an important model organism in various fields of biology. In this paper, we present a comprehensive tissue-wide spatial metabolomics dataset for lampreys, where 14 distinct tissues were analyzed using liquid chromatography-mass spectrometry (LC-MS) in both positive and negative ion modes. The dataset has been fully validated using internal standard and pooled quality control samples and is readily accessible at the UCSD Metabolomics Workbench. This dataset serves as a valuable resource for researchers using lampreys as a model organism. Additionally, it acts as a benchmark metabolomics dataset for evaluating new algorithms and software tools and comparing them with previously published results. A lamprey spatial metabolomics database is also provided to support studies utilizing lampreys as an animal model, and to complement and validate other spatial metabolomics studies on lampreys conducted with mass spectrometry imaging or other techniques., (© 2024. The Author(s).)

Digital light processing (DLP)-based bioprinting technology holds immense promise for the advancement of hydrogel constructs in biomedical applications. However, creating high-performance hydrogel constructs with this method is still a challenge, as it requires balancing the physicochemical properties of the matrix while also retaining the cellular activity of the encapsulated cells. Herein, we propose a facile and practical strategy for the 3D bioprinting of high-performance hydrogel constructs through the in-situ birth of stem cell spheroids. The strategy is achieved by loading the cell/dextran microdroplets within gelatin methacryloyl (GelMA) emulsion, where dextran functions as a decoy to capture and aggregate the cells for bioprinting while GelMA enables the mechanical support without losing the structural complexity and fidelity. Post-bioprinting, the leaching of dextran results in a smooth curved surface that promotes in-situ birth of spheroids within hydrogel constructs. This process significant enhances differentiation potential of encapsulated stem cells. As a proof-of-concept, we encapsulate dental pulp stem cells (DPSCs) within hydrogel constructs, showcasing their regenerative capabilities in dentin and neovascular-like structures in vivo . The strategy in our study enables high-performance hydrogel tissue construct fabrication with DLP-based bioprinting, which is anticipated to pave a promising way for diverse biomedical applications., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors.)

The neonicotinoid pesticide acetamiprid has been widely used in agricultural pest control and was frequently detected in the water environment. There have been some studies of the toxic effects of acetamiprid on fish, but studies on aquatic lower vertebrates are still very limited. As a primitive jawless vertebrate, Lethenteron reissneri has a special position in evolution and is now listed as a national second level protected animal in China. The present study aimed to investigate the toxic effect of acetamiprid on the liver of L. reissneri larvae. A conjoint analysis of the transcriptomics and metabolomics was performed to determine the responses of L. reissneri larvae liver to acetamiprid at different concentrations (L for low concentration 25 mg/L and H for high concentration 100 mg/L). Even low concentrations of acetamiprid can cause significant liver damage to L. reissneri larvae in a short period. In omics analyses, 2141 differentially expressed genes (DEGs) and 183 differentially abundant metabolites (DAMs) were identified in the H/Control group, and 229 DEGs and 144 DAMs were identified in the L/C group. Correlation analyses revealed acetamiprid affected the metabolic pathways of L. reissneri larvae liver such as the glycerophospholipid metabolism and arachidonic acid metabolism. This study not only enriches the basis for understanding the toxic effect of acetamiprid exposure to L. reissneri larvae liver and provides more information on the breeding and conservation of L. reissneri, but also further causes attention on toxicity risk from acetamiprid to aquatic lower vertebrate species., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Qingwei Li reports administrative support, article publishing charges, and equipment, drugs, or supplies were provided by Chinese National Natural Science Foundation. Jiali Lu reports administrative support, article publishing charges, and equipment, drugs, or supplies were provided by Applied Basic Research Project of the Science and Technology Department of Liaoning Province. Jiali Lu reports administrative support, article publishing charges, and equipment, drugs, or supplies were provided by the Project of the Educational Department of Liaoning Province. Xiaoping Song reports administrative support, article publishing charges, and equipment, drugs, or supplies were provided by Dalian Youth Science and Technology Star Fund Project. If there are other authors, they 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Immune checkpoint blockade (ICB) therapy, while showing promise in various cancers, exhibits limited effectiveness in hepatic carcinoma due to the tumor's immunosuppressive microenvironment (TME) and challenges associated with immune cell infiltration. Efforts to transform the "cold" TME into an "inflamed" state, notably through chemo-immunotherapy, have sparked interest due to their potential to induce immunogenic cell death and augment the infiltration of cytotoxic T lymphocytes (CTLs). Nonetheless, the efficacy of chemo-immunotherapy is often compromised by suboptimal pharmacokinetics, poor tumor accumulation, and off-target toxicity. Herein, in response, we introduce an innovative, milder thermal therapeutic approach leveraging gold nano frameworks with mesopores for the targeted delivery of the immunostimulant imiquimod and NIR-II photothermal therapy. This strategy employs targeted molecule modifications to ensure precise tumor targeting, guided by photoacoustic imaging. Subsequent to mild thermal treatment, there is a release of immunogenic proteins (CRT and HSP90), enhancing tumor immunogenicity. Assisted by imiquimod, substantial CTL infiltration occurs, accompanied by pro-inflammatory factor release (TNF-α, IL-6), transforming M2 macrophages into the M1 phenotype. Ultimately, the proposed strategy combines PD-L1/PD-1 blockade, imiquimod and mild thermal treatment to synergistically enhance tumor immunogenicity, remodel the TME, and restrain hepatic carcinoma, making strides in ICB synergistic immune-thermal therapy.

Lodging largely affects yield, quality and mechanical harvesting of maize. Stalk strength is one of the major factors that affect maize lodging. Although plant cell wall components including lignin and cellulose were known to be associated with stalk strength and lodging resistance, spatial accumulation of specific lignin monomers and cellulose in different tissues and their association with stalk strength in maize was not clearly understood. In this study, we found that both G and S lignin monomers accumulate highest in root, stem rind and leaf vein. Consistently, most lignin biosynthetic genes were expressed higher in root and stem than in other tissues. However, cellulose appears to be lowest in root. There are only mild changes of G lignin and cellulose in different internodes. Instead, we noticed a dramatic decrease of S-lignin accumulation and lignin biosynthetic gene expression in 2 nd to 4 th internodes wherein stem breakage usually occurs, thereby revealing a few candidate lignin biosynthetic genes associated with stalk strength. Moreover, stalk strength is positively correlated with G, S lignin, and cellulose, but negatively correlated with S/G ratio based on data of maize lines with high or low stalk strength. Loss-of-function of a caffeic acid o-methyltransferase (COMT), which is involved in S lignin biosynthesis, in the maize bm3 mutant, leads to lower stalk strength. Our data collectively suggest that stalk strength is determined by tissue-specific accumulation of lignin monomers and cellulose, and manipulation of the cell wall components by genetic engineering is vital to improve maize stalk strength and lodging resistance., 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 Masson SAS. All rights reserved.)

Background: Prenatal depression is associated with adverse health outcomes for both mothers and their children. The worldwide COVID-19 pandemic has presented new risks and challenges for expectant mothers. The aims of the study were to investigate the underlying mechanism between COVID-19 risk perception of Chinese pregnant women and their prenatal depressive symptoms and potential protective factors such as family sense of coherence (FSOC)., Method: A total of 181 Chinese pregnant women (M age = 31.40 years, SD = 3.67, ranged from 23 to 43) participated in an online survey from April 22 to May 16, 2020. Risk perception and negative emotions (fear and anxiety) related with COVID-19, FSOC, and prenatal depressive symptoms were assessed., Results: The experience of maternal COVID-19 related negative emotion fully mediated the positive relationship between COVID-19 risk perception and prenatal depressive symptoms of pregnant women (β = 0.12, 95% CI [0.06, 0.19]). When confronting COVID-19 related fear and anxiety, expectant mothers from higher coherent families experienced a significantly lower level of prenatal depressive symptoms., Conclusions: Contextual negative emotional experience was demonstrated to explain how risk perception impacts depressive symptoms during severe public health crisis for pregnant women. FSOC may be a psychological resource protecting pregnant women from experiencing adverse psychological outcomes during COVID-19 pandemic., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cooked off-flavor was produced during the processing of concentrated peach puree (CPP), which led to aroma deterioration. Enzymatic treatment was beneficial in eliminating off-flavors and improving the aroma quality. Herein, the efficacy of glycosidase (AR2000), glucose oxidation (GOD), and their combination on the inhibition of off-flavors and aroma enhancement were evaluated. Compared with CPP, contents of benzaldehyde, benzyl alcohol, nonanal, and linalool increased by 198%, 1222%, 781%, and 71% after AR2000 treatment via the metabolisms of shikimate, glucose, linoleic acid, and linolenic acid, leading to the strengthening of floral and grassy. Due to the removal of 1-octen-3-one via linolenic acid metabolism, cooked off-flavor could be significantly weakened by GOD. Furthermore, Furthermore, the combination of AR2000 and GOD could not only inhibit the production of 1-octen-3-one to weaken the cooked note but also enhance grassy and floral attributes via the increase of aldehydes and alcohols., 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. Published by Elsevier Ltd.)

Introduction: The therapeutic needs of women with diminished ovarian reserve (DOR), coupled with the increasing application of acupuncture in improving ovarian function, have highlighted the need to verify the efficacy and safety of acupuncture for DOR. This study aims to provide high-quality evidence by evaluating both ovarian reserve and in vitro fertilisation (IVF) outcomes., Methods and Analysis: A large-scale, multicentre, randomised controlled trial will be carried out across seven hospitals in China. 400 women with DOR will be randomised in a 1:1 ratio to an acupuncture group or a sham acupuncture group. Acupuncture or sham acupuncture will consist of 36 sessions per participant over 12 weeks. The primary outcome will be the change in antral follicle count (AFC) at week 12 from baseline. Secondary outcomes are AFC at week 24, the serum levels of basal follicle-stimulating hormone and anti-Mullerian hormone at weeks 12 and 24, the scores of the Self-Rating Anxiety Scale at weeks 12 and 24, clinical pregnancy rate, and IVF embryo transfer related outcomes. Any adverse events during treatment will be documented., Ethics and Dissemination: The study protocol has been approved by all the participating institutions. Written informed consent will be obtained prior to participant enrolment. The results of this study will be published in peer-reviewed publications., Trial Registration Number: ChiCTR2200062295 PROTOCOL VERSION: V2.0-20220317., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Ethical behaviour in nursing practice is integral to establishing a harmonious nurse-patient relationship and improving the quality of care. A multitude of factors shapes such behaviour. Therefore, it is crucial to understand the interplay between these factors. Research objectives: This study aimed to explore the mechanisms underlying the influence of moral sensitivity on nurses' ethical behaviour and clarify the mediating role of moral courage. Research design: This cross-sectional quantitative study was conducted between July and August 2023. Participants and Research Context: The sample comprised 465 clinical nurses from three tertiary hospitals in Zhengzhou City, Henan Province, China. Data were collected using the Chinese version of the Moral Sensitivity Questionnaire-Revised Version, Nurses' Moral Courage Scale, and Ethical Behaviour Scale for Nurses. Data analysis was performed with SPSS 26.0 and AMOS 24.0, using descriptive statistics, Pearson correlation analysis, structural equation modelling, and bootstrapping methods. Ethical considerations: This study was approved by the Ethical Review Committee of Life Sciences of Zhengzhou University, China. Results: The participants were predominantly female (95.1%), with a mean age of 31.9 years. Moral courage and moral sensitivity were positively correlated with ethical behaviour. Moral sensitivity was positively associated with moral courage. Moral courage partially mediates the relationship between moral sensitivity and ethical behaviour. The indirect effect of nurses' moral sensitivity on ethical behaviour was quantified through moral courage (indirect effect = 0.290). Conclusion: Moral courage intermediates nurses' moral sensitivity and ethical behaviour. This conclusion provides nursing administrators with the insight that improving clinical nurses' moral sensitivity and courage can contribute to ensuring appropriate ethical behaviour., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The immunological mechanisms underlying chronic colitis are poorly understood. T follicular helper (T FH ) cells are critical in helping B cells during germinal center reactions. In a T cell transfer colitis model, a lymphoid structure composed of mature dendritic cells (DCs) and T FH cells was found within T cell zones of colonic lymphoid follicles. T FH cells were required for mature DC accumulation, the formation of DC-T cell clusters and colitis development. Moreover, DCs promoted T FH cell differentiation, contributing to colitis development. A lineage-tracing analysis showed that, following migration to the lamina propria, T FH cells transdifferentiated into long-lived pathogenic T H 1 cells, promoting colitis development. Our findings have therefore demonstrated the reciprocal regulation of T FH cells and DCs in colonic lymphoid follicles, which is critical in chronic colitis pathogenesis., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Developing microbial consortiums is necessary for microbial enhanced oil recovery (MEOR) in heavy crude oil production. The aqueous phase of produced fluid has long been considered an ideal source of microorganisms for MEOR. However, it is recently found that rich microorganisms (including hydrocarbon-degrading bacteria) are present in the crude oil phase, which is completely different from the aqueous phase of produced fluid. So, in this study, the microbial consortia from the crude oil phase of produced fluids derived from four wells were enriched, respectively. The microbial community structure during passage was dynamically tracked, and the response of enriched consortia to successive disturbance of environmental factors was investigated. The results showed the crude oil phase had high microbial diversity, and the original microbial community structure from four wells was significantly different. After ten generations of consecutive enrichment, different genera were observed in the four enriched microbial consortia, namely, Geobacillus, Bacillus, Brevibacillus, Chelativorans, Ureibacillus, and Ornithinicoccus. In addition, two enriched consortia (eG1614 and eP30) exhibited robustness to temperature and oxygen perturbations. These results further suggested that the crude oil phase of produced fluids can serve as a potential microbial source for MEOR., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

3-phosphoinositide-dependent protein kinase-1 (PDK-1) is a key kinase regulating the activity of the PI3K/AKT pathway and a major regulator of the AGC protein kinase family. It is essential in the physiological activities of cells, embryonic development, individual development and immune response. In this study, we have identified for the first time an analogue of PDK-1 in the most primitive vertebrate, lamprey, and named it PDK-1-like. The protein sequence similarity of lamprey PDK-1-like to human, mouse, chicken, African xenopus and zebrafish PDK-1 were 64.4 %, 64.5 %, 65.0 %, 61.3 % and 63.2 %, respectively. The phylogenetic tree showed that PDK-1-like of lamprey were located at the base of the vertebrate branch, in line with the trend of biological evolution. Meanwhile, homology analysis showed that PDK-1 proteins across species shared a conserved kinase structural domain and a Pleckstrin Homology (PH) domain. Genomic synteny analysis revealed that the large-scale duplication blocks were not found in lamprey genome and neighbor genes of lamprey PDK-1-like presented dramatic differences compared with jawed vertebrates. More importantly, qPCR analysis showed that PDK-1-like was widely expressed in lamprey. Its mRNA expression levels varied in response to different pathogenic stimuli, and its expression was generally up-regulated under Polyinosinic-Polycytidylic acid (Poly(I:C)) stimulation. Pearson's correlation analysis showed that PDK-1-like was involved in co-expressed with MyD88-independent TLR-3 pathway during the immune response of lamprey, instead of MyD88-dependent TLR-3 pathway. In summary, our composite results offer valuable clues to the origin and evolution of PDK-1, and imply that PDK-1 s are among the most ancestral immune regulators in vertebrates., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Source-free domain adaptation (SFDA) shows the potential to improve the generalizability of deep learning-based face anti-spoofing (FAS) while preserving the privacy and security of sensitive human faces. However, existing SFDA methods are significantly degraded without accessing source data due to the inability to mitigate domain and identity bias in FAS. In this paper, we propose a novel Source-free Domain Adaptation framework for FAS (SDA-FAS) that systematically addresses the challenges of source model pre-training, source knowledge adaptation, and target data exploration under the source-free setting. Specifically, we develop a generalized method for source model pre-training that leverages a causality-inspired PatchMix data augmentation to diminish domain bias and designs the patch-wise contrastive loss to alleviate identity bias. For source knowledge adaptation, we propose a contrastive domain alignment module to align conditional distribution across domains with a theoretical equivalence to adaptation based on source data. Furthermore, target data exploration is achieved via self-supervised learning with patch shuffle augmentation to identify unseen attack types, which is ignored in existing SFDA methods. To our best knowledge, this paper provides the first full-stack privacy-preserving framework to address the generalization problem in FAS. Extensive experiments on nineteen cross-dataset scenarios show our framework considerably outperforms state-of-the-art methods.

Background: Increasing evidence suggested that immune abnormalities involved in the pathophysiology of schizophrenia. However, the relationship between immunity and clinical features has not been clarified. The aim of this study was to measure the plasma levels of tumor necrosis factor alpha (TNF-α) and soluble TNF-α receptor 1 (sTNF-α R1) and to investigate their association with agitation in first episode patients with schizophrenia (FEPS)., Methods: The plasma TNF-α and sTNF-α R1 levels were measured using sandwich enzyme-linked immunosorbent assay (ELISA) in the FEPS with (n = 36) and without agitation (n = 49) symptoms, and healthy controls (HCs, n = 54). The psychopathology was assessed by the Positive and Negative Syndrome Scale (PANSS), and the agitation symptoms were evaluated by the PANSS excitatory component (PANSS-EC)., Results: The plasma TNF-α levels in patients with and without agitation symptoms were significantly higher than those in HCs. The patients with agitation had significantly higher plasma TNF-α levels compared to the patients without agitation. There were no significant differences in the sTNF-α R1 levels among the three groups. Furthermore, the plasma TNF-α levels were positively correlated with the PANSS total score, Positive and General psychopathological subscores, and PANSS-EC score in the FEPS, but the relationships were not found for the plasma sTNF-α R1 levels., Conclusions: These results suggested that TNF-α might play an important role in the onset and development of agitation symptoms of schizophrenia., (© 2024. The Author(s).)

Haloarchaea with the capacity to degrade alkanes is promising to deal with petroleum pollution in hypersaline environments. However, only a limited number of haloarchaeal species are investigated, and their pathway and mechanism for alkane degradation remain unclear. In this study, Halogranum rubrum RO2-11, a haloarchaeal strain, verified the ability to degrade kerosene and hexadecane in 184 g/L NaCl, with 53% and 52% degradation rates after 9 and 4 days, respectively. Genome sequencing and gene annotation indicated that strain RO2-11 possesses a complete potential alkane-degrading pathway, of which alkane hydroxylases may include CYP450, AlmA, and LadA. Transcriptome and metabolome analyses revealed that the upregulation of related genes in TCA cycle, lysine biosynthesis, and acetylation may help improve hexadecane degradation. Additionally, an alternative degrading pathway of hexadecane based on dual-terminal β-oxidation may occur in strain RO2-11. It is likely to be the first report of alkane degradation by the genus Halogranum, which may be helpful for applications of oil-pollution bioremediation under high-salt conditions., 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.)

Schizophrenia patients with tardive dyskinesia (TD) are associated with accelerated biological aging, immunological dysfunction, and premature morbidity and mortality. Older individuals are particularly vulnerable to TD development. As a characteristic of immunosenescence, alterations in the relative proportions of naïve or memory T cell subpopulations may be negatively or positively associated with brain structure abnormalities; however, whether these changes are correlated with TD remains unclear. In this study, we investigated correlations between distributions of T cell phenotypes and brain structure abnormalities (especially white matter) in schizophrenia patients with (TD) and without (NTD) TD (n = 50 and 58, respectively) relative to healthy controls (HC, n = 41). Immune markers, including naïve (CD45RA+), memory (CD45RO+), and apoptotic (CD95+) CD4+ and CD8+ T cells, were examined by flow cytometry, as were the intracellular levels of cytokines (interferon (IFN)-γ, interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α) in CD8 + CD45RA + CD95+ and CD8 + CD45RO + CD95+ T cells. MRI was employed to evaluate the fractional anisotropy (FA) of white matter tracts and subcortical volumes, following published routines. The percentage of CD8 + CD45RO + CD95+ T cells was higher in TD compared with NTD and HC groups and correlated with the choroid plexus volume in TD group. The intracellular level of IFN-γ in CD8 + CD45RO + CD95+ T cells, the FA of the fornix/stria terminalis, and the pallidum volume were correlated with orofacial TD, whereas the FAs of the inferior fronto-occipital fasciculus, cingulum, and superior longitudinal fasciculus were correlated with limb-truncal TD. These findings provide preliminary evidence that the association between immunosenescence-related T cell subpopulations and brain structure may underline the pathological process of TD., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)