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Tao Geng, Zhi-Yuan Song, Jing-Xian Xing, Bing-Xun Wang, Shi-Peng Dai, Ze-Sheng Xu Department of Cardiovascular Disease, Cangzhou Central Hospital of Tianjin Medical University, Cangzhou, Hebei Province, People’s Republic of ChinaCorrespondence: Ze-Sheng XuDepartment of Cardiovascular Disease, Cangzhou Central Hospital of Tianjin Medical University, No. 16, Xinhua West Road, Cangzhou, Hebei Province, People’s Republic of ChinaTel +86-15003172868Email xutuqian848141@163.comPurpose: Myocardial ischemia-reperfusion injury primarily causes myocardial infarction (MI), which is manifested by cell death. Angiogenesis is essential for repair and regeneration in cardiac tissue after MI. In this study, we aimed to investigate the effect of exosomes derived from the serum of MI patients in angiogenesis and its related mechanism.Patients and Methods: Exosomes, isolated from serum, were collected from MI (MI-exosome) and control (Con-exosome) patients. After coculturing with human umbilical vein endothelial cells, MI-exosome promoted cell proliferation, migration, and tube formation.Results: The results revealed that the production and release of MI-exosome were associated with cardiomyocytes. Moreover, microarray assays demonstrated that miRNA-143 was significantly decreased in MI-exosome. Meanwhile, the overexpression and knockdown of miRNA-143 could inhibit and enhance angiogenesis, respectively. Furthermore, the effect of exosomal miRNA-143 on angiogenesis was mediated by its targeting gene, insulin-like growth factor 1 receptor (IGF-IR), and was associated with the production of nitric oxide (NO).Conclusion: Taken together, exosomes derived from the serum of patients with MI promoted angiogenesis through the IGF-IR/NO signaling pathway. The results provide novel understanding of the function of exosomes in MI.Keywords: myocardial ischemia, exosome, miRNA-143, insulin-like growth factor 1 receptor, angiogenesis

Background: The use of immunotherapy in mismatch repair proficient colorectal cancer (pMMR-CRC) or pancreatic adenocarcinoma (PDAC) is associated with limited efficacy. DAPPER (NCT03851614) is a phase 2, basket study randomizing patients with pMMR CRC or PDAC to durvalumab with olaparib (durvalumab + olaparib) or durvalumab with cediranib (durvalumab + cediranib)., Methods: PDAC or pMMR-CRC patients were randomized to either durvalumab+olaparib (arm A), or durvalumab + cediranib (arm B). Co-primary endpoints included pharmacodynamic immune changes in the tumor microenvironment (TME) and safety. Objective response rate, progression-free survival (PFS) and overall survival (OS) were determined. Paired tumor samples were analyzed by multiplexed immunohistochemistry and RNA-sequencing., Results: A total of 31 metastatic pMMR-CRC patients were randomized to arm A (n = 16) or B (n = 15). In 28 evaluable patients, 3 patients had stable disease (SD) (2 patients treated with durvalumab + olaparib and 1 patient treated with durvalumab + cediranib) while 25 had progressive disease (PD). Among patients with PDAC (n = 19), 9 patients were randomized to arm A and 10 patients were randomized to arm B. In 18 evaluable patients, 1 patient had a partial response (unconfirmed) with durvalumab + cediranib, 1 patient had SD with durvalumab + olaparib while 16 had PD. Safety profile was manageable and no grade 4-5 treatment-related adverse events were observed in either arm A or B. No significant changes were observed for CD3+/CD8+ immune infiltration in on-treatment biopsies as compared to baseline for pMMR-CRC and PDAC independent of treatment arms. Increased tumor-infiltrating lymphocytes at baseline, low baseline CD68+ cells and different immune gene expression signatures at baseline were associated with outcomes., Conclusions: In patients with pMMR-CRC or PDAC, durvalumab + olaparib and durvalumab + cediranib showed limited antitumor activity. Different immune components of the TME were associated with treatment outcomes., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This work demonstrates a dual-functional tunable terahertz metamaterial absorber based on thermally controllable vanadium dioxide (VO 2 ) and electrically tunable graphene. The switchable absorption functions could be obtained in the same metamaterial, which consists of alternating stacked cross-cut graphene disks (CGDs) and VO 2 square rings (VSRs) separated by an ultra-thin dielectric film placed on a continuous gold mirror. The metallic state of VSRs is the dominant factor for the broadband absorption function, resulting in a broadband absorption of 4.746 THz. Based on this, the Fermi energy level of CGDs increases to 0.7 eV, which could broaden the absorption bandwidth to 5.398 THz. When the VSRs are in the insulating state, CGDs dominate the absorption, and the suggested device switches to the dual-band absorption function. These two absorption peaks appear to be larger than 97% and their frequencies could be dynamically controlled by the Fermi energy level of CGDs. In addition to the excellent absorption characteristics of dynamic switching of two different functions, polarization insensitivity and large-angle tolerance are also advantages of this work, which could provide new insights and guidance for the study of dynamically tunable metamaterial absorbers.

Edible offal of farmed animals can accumulate cadmium (Cd). However, no studies have investigated Cd bioavailability and its health effects. Here, based on mouse models, market pork kidney samples exhibited high Cd relative bioavailability of 74.5 ± 11.2% (n = 26), close to 83.8 ± 7.80% in Cd-rice (n = 5). This was mainly due to high vitamin D 3 content in pork kidney, causing 1.7-2.3-fold up-regulated expression of duodenal Ca transporter genes in mice fed pork kidney compared to mice fed Cd-rice, favoring Cd intestinal absorption via Ca transporters. However, although pork kidney was high in Cd bioavailability, subchronic low-dose (5% in diet) consumption of two pork kidney samples having 0.48 and 0.97 μg Cd g -1 dw over 35 d did not lead to significant Cd accumulation in the tissue of mice fed Cd-free rice but instead remarkably decreased Cd accumulation in the tissue of mice fed Cd-rice (0.48 μg Cd g -1 ) by ∼50% and increased abundance of gut probiotics ( Faecalibaculum and Lactobacillus ). Overall, this study contributed to our understanding of the bioavailability and health effects associated with Cd in edible offal, providing mechanistic insights into pork kidney consumption safety based on Cd bioavailability.

To deepen the recognition of changes in industrial water use with socio-economic development, a "double-layer nested" structural decomposition analysis has been proposed to decompose the influence of the drivers of industrial water use change by sectors in China from 2002 to 2020. The results showed that the scale expansion factors represented by consumption, investment, and export were the main factors for the growth of industrial water use in different sectors, among which the expansion effect of per capita consumption grew faster. Additionally, there were obvious differences in the major drivers of industrial scale expansion between different sectors, which directly drove the industrial structure change. The production process water use effect and water reuse effect were the main factors to curb the growth of industrial water use. The accumulation of both had completely offset the positive effect of industrial scale expansion during the period, reducing industrial water consumption by 11.2 billion m3. However, the production process water use changes in metal extraction, smelting, and processing and energy processing sectors such as electric power had a smaller negative effect, leading to the potential for improving industrial water efficiency solely through a relatively small improvement in water resource reuse. Therefore, it is necessary to strengthen industrial water conservation management based on the differences in the impact of various sectors to promote the transformation and upgradation of industrial production and consumption structures, and to avoid another increase in industrial water use in China.

An enantioselective copper-catalyzed 1,2-arylboration reaction of enamines has been developed by employing ( R )-xyl-BINAP as a chiral ligand. A number of chiral borate-containing 3,3'-disubstituted isoindolinones were obtained in moderate to good yields and good to excellent enantioselectivities from the reactions of N -( o -iodobenzoyl)enamines and bis(pinacolato)diboron (B 2 pin 2 ) under mild reaction conditions. Synthetic transformations of the products were conducted to demonstrate the practicality of this reaction.

Fundamental frequency (F0) has been widely studied and used in the context of speaker discrimination and forensic voice comparison casework, but most previous studies focused on long-term F0 statistics. Lexical tone, the linguistically structured and dynamic aspects of F0, has received much less research attention. A main methodological issue lies on how tonal F0 should be parameterized for the best speaker discrimination performance. This paper compares the speaker discriminatory performance of three approaches with lexical tone modeling: discrete cosine transform (DCT), polynomial curve fitting, and quantitative target approximation (qTA). Results show that using parameters based on DCT and polynomials led to similarly promising performance, whereas those based on qTA generally yielded relatively poor performance. Implications modeling surface tonal F0 and the underlying articulatory processes for speaker discrimination are discussed.

Objective: To investigate the effects of modified endoscopic retrograde appendicitis therapy (mERAT) on the treatment of children with different severities of acute appendicitis. Methods: This study was a case-control study. A total of 586 children with acute appendicitis, who were admitted to the Pediatric Department of Second Affiliated Hospital of Air Force Medical University between January 2019 and November 2023, were selected as the research subjects. According to the severity of the disease, the patients were divided into simple appendicitis group, suppurative appendicitis group and perforated appendicitis group. The baseline data, hospitalization treatment and costs, outcomes, and recurrence in each group were analyzed, and the difference in the effectiveness of mERAT between the groups were compared by Kruskal-Wallis H test and χ 2 test. Results: Among 586 children, there were 338 males and 248 females. The age at onset was 7.0 (4.6, 9.4) years. There were 475 cases of simple appendicitis, 78 cases of suppurative appendicitis, and 33 cases of perforated appendicitis. There were no significant differences in age and gender among the three groups ( F =0.59, χ 2 =3.31, both P >0.05). However, there were statistically significant differences in body temperature, white blood cell counts, neutrophil percentage, lymphocyte percentage, nausea or vomiting, right lower abdominal pain, umbilical pain, right lower abdominal tenderness, and right lower abdominal rebound pain ( H =7.56, 161.52, 169.11, and 169.61, χ 2 =12.05, 13.82, 12.05, 7.74, 20.35, and 94.61, all P <0.05). Also, the treatment time, postoperative hospital stay, total hospital stay, and cost showed statistically significant differences ( H= 4.70, 33.66, 34.99, 30.37, all P <0.05). There was no significant difference in the initial treatment success rate (98.1% (466/475) vs. 98.7% (77/78) vs. 90.9% (30/33), P =0.057). During the 30 (23, 36) months of follow-up, the recurrence rate was 7.9% (35/433) in the simple appendicitis group, 20.8% (15/72) in the suppurative appendicitis group, and 30.0% (9/30) in the perforated appendicitis group, with a statistically significant difference ( χ 2 =23.56, P< 0.001). Among the children with recurrent appendicitis, 15 cases still chose mERAT, of them 11 cases (31.2%) had simple appendicitis, 2 cases (2/15) had suppurative appendicitis, and 2 cases (2/9) had perforated appendicitis.The latest time to recurrence in the 3 groups was 32, 35 and 10 months, respectively. Conclusion: Treatment with mERAT has a good effect in pediatric simple appendicitis, but has a higher recurrence rate despite a better initial treatment success rate in suppurative appendicitis and perforated appendicitis.

Intelligent manufacturing technologies, including databases, mathematical modeling, and information systems have played a significant role in process control, production management, and supply chain management in traditional Chinese medicine(TCM) industry. However, their ability to process and utilize unstructured data, such as research and development reports, batch production records, quality inspection records, and supplier documents, is relatively weak. For text, images, language, and other unstructured data, generative artificial intelligence(AI) technology has shown strong potential for development in extracting information, extracting knowledge, semantic retrieval, and content generation. Generative AI is expected to provide a feasible set of tools for the utilization of unstructured data resources in the TCM industry. Based on years of research and industrial application experience in TCM intelligent manufacturing technology, this study reviewed the current situation of intelligent manufacturing in TCM and the utilization of unstructured data, analyzed the application value of generative AI in the TCM manufacturing process and supply chain, summarized four typical application scenarios, including intelligent pharmaceutical knowledge base/knowledge graph, intelligent on-the-job trai-ning, intelligent production quality control, and intelligent supply chain. Furthermore, this study also explained the data collection and processing, business process design, application potential, and value of each scenario based on industry demands. Finally, based on the integration of generative AI and TCM industrial models, the study proposed a preliminary concept of a smart industrial brain for TCM, aiming to provide a reference for the application of AI technology in the field of TCM manufacturing.

A growing number of studies in forensic voice comparison have explored how elements of phonetic analysis and automatic speaker recognition systems may be integrated for optimal speaker discrimination performance. However, few studies have investigated the evidential value of long-term speech features using forensically-relevant speech data. This paper reports an empirical validation study that assesses the evidential strength of the following long-term features: fundamental frequency (F0), formant distributions, laryngeal voice quality, mel-frequency cepstral coefficients (MFCCs), and combinations thereof. Non-contemporaneous recordings with speech style mismatch from 75 male Australian English speakers were analyzed. Results show that 1) MFCCs outperform long-term acoustic phonetic features; 2) source and filter features do not provide considerably complementary speaker-specific information; and 3) the addition of long-term phonetic features to an MFCCs-based system does not lead to meaningful improvement in system performance. Implications for the complementarity of phonetic analysis and automatic speaker recognition systems are discussed., 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.)

NK cells have been shown to exhibit inflammatory and immunoregulatory functions in a variety of healthy and diseased settings. In the context of chronic viral infection and cancer, distinct NK cell populations that inhibit adaptive immune responses have been observed. To understand how these cells arise and further characterize their immunosuppressive role, we examined in vitro conditions that could polarize human NK cells into an inhibitory subset. TGF-β1 has been shown to induce regulatory T cells in vitro and in vivo; we therefore investigated if TGF-β1 could also induce immunosuppressive NK-like cells. First, we found that TGF-β1/IL-15, but not IL-15 alone, induced CD103+CD49a+ NK-like cells from peripheral blood NK cells, which expressed markers previously associated with inhibitory CD56+ innate lymphoid cells, including high expression of GITR and CD101. Moreover, supernatant from ascites collected from patients with ovarian carcinoma also induced CD103+CD49a+ NK-like cells in vitro in a TGF-β-dependent manner. Interestingly, TGF-β1/IL-15-induced CD103+CD56+ NK-like cells suppressed autologous CD4+ T cells in vitro by reducing absolute number, proliferation, and expression of activation marker CD25. Collectively, these findings provide new insight into how NK cells may acquire an inhibitory phenotype in TGF-β1-rich environments., (Copyright © 2024 by The American Association of Immunologists, Inc.)

Two-dimensional metal-organic networks (2D MONs) having heterogeneous coordination nodes (HCNs) could exhibit excellent performance in catalysis and optoelectronics because of the unbalanced electron distribution of the coordinating metals. Therefore, the design and construction of 2D MONs with HCNs are highly desirable but remain challenging. Here, we report the construction of 2D organometallic coordination networks with an organic Kagome lattice and a semiregular metal lattice on Au(111) via the in situ formation of HCNs. Using a bifunctional precursor 1,4-dibromo-2,5-diisocyanobenzene, the coordination of isocyano with Au adatom on a room-temperature Au(111) yielded metal-organic coordination chains with isocyano-Au-isocyano nodes. In contrast, on a high-temperature Au(111), a selective debromination/coordination cascade reaction occurred, affording 2D organometallic coordination networks with phenyl-Au-isocyano nodes. By combining scanning tunneling microscopy and density functional theory calculations, we determined the structures of coordination products and the nature of coordination nodes, demonstrating a thermodynamically favorable pathway for forming the phenyl-Au-isocyano nodes.

Salmonella enterica is comprised of genetically distinct 'serovars' that together provide an intriguing model for exploring the genetic basis of pathogen evolution. Although the genomes of numerous Salmonella isolates with broad variations in host range and human disease manifestations have been sequenced, the functional links between genetic and phenotypic differences among these serovars remain poorly understood. Here, we conduct high-throughput functional genomics on both generalist (Typhimurium) and human-restricted (Typhi and Paratyphi A) Salmonella at unprecedented scale in the study of this enteric pathogen. Using a comprehensive systems biology approach, we identify gene networks with serovar-specific fitness effects across 25 host-associated stresses encountered at key stages of human infection. By experimentally perturbing these networks, we characterize previously undescribed pseudogenes in human-adapted Salmonella. Overall, this work highlights specific vulnerabilities encoded within human-restricted Salmonella that are linked to the degradation of their genomes, shedding light into the evolution of this enteric pathogen., (© 2024. The Author(s).)

The innate lymphoid cell (ILC) family is composed of heterogeneous innate effector and helper immune cells that preferentially reside in tissues where they promote tissue homeostasis. In cancer, they have been implicated in driving both pro- and anti-tumor responses. This apparent dichotomy highlights the need to better understand differences in the ILC composition and phenotype within different tumor types that could drive seemingly opposite anti-tumor responses. Here, we characterized the frequency and phenotype of various ILC subsets in melanoma metastases and primary epithelial ovarian tumors. We observed high PD-1 expression on ILC subsets isolated from epithelial ovarian tumor samples, while ILC populations in melanoma samples express higher levels of LAG-3. In addition, we found that the frequency of cytotoxic ILCs and NKp46 + ILC3 in tumors positively correlates with monocytic cells and conventional type 2 dendritic cells, revealing potentially new interconnected immune cell subsets in the tumor microenvironment. Consequently, these observations may have direct relevance to tumor microenvironment composition and how ILC subset may influence anti-tumor immunity., Competing Interests: Dr. Pamela Ohashi is on Scientific Advisory Boards for Providence Therapeutics, Treadwell Therapeutics, Tikva Allocell and Rondo Therapeutics. Inc. Dr. Ohashi holds a sponsored research agreement with Providence Therapeutics. No potential conflict of interest was reported by the other authors., (© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Purpose: The current study investigated English prosodic focus marking by autistic and typically developing (TD) Cantonese trilingual children, and examined the potential differences in this regard compared to native English-speaking children., Method: Forty-eight participants were recruited with 16 speakers for each of the three groups (Cantonese-speaking autistic [CASD], Cantonese-speaking TD [CTD], and English-speaking TD [ETD] children), and prompt questions were designed to elicit desired focus type (i.e., broad, narrow, and contrastive focus). Mean duration, mean fundamental frequency ( F 0), F 0 range, mean intensity, and F 0 curves were used as the acoustic correlates for linear mixed-effects model fitting and functional data analyses in relation to groups and focus conditions (i.e., broad, narrow, and contrastive pre-, on-, and post-focus)., Results: The CTD group had post-focus compression (PFC) patterns via reducing mean duration, narrowing F 0 range, and lowering mean F 0, F 0 curve, and mean intensity for words under both narrow and contrastive post-focus conditions, while the CASD group only had shortened mean duration and lowered F 0 curves. However, neither the CTD group nor CASD group showed much of on-focus expansion (OFE) patterns. The ETD group marked OFE by increasing mean duration, mean F 0, mean intensity, and higher F 0 curve for words under on-focus conditions., Conclusions: The CTD group utilized more acoustic cues than the CASD group when it comes to PFC. The ETD group differed from the CASD and CTD groups in the use of OFE. Furthermore, both the CASD and CTD groups showed positive first language transfer in the use of duration and intensity and, potentially, successful acquisition in the use of F 0 for prosodic focus marking. Meanwhile, the differences in the use of OFE between the Cantonese-speaking and English-speaking groups, not PFC, might indicate that Cantonese-speaking children acquire PFC prior to OFE.

Importance: Guidelines recommend deprescribing opioids in older adults due to risk of adverse effects, yet little is known about patient-clinician opioid deprescribing conversations., Objective: To understand the experiences of older adults and primary care practitioners (PCPs) with using opioids for chronic pain and discussing opioid deprescribing., Design, Setting, and Participants: This qualitative study conducted semistructured individual qualitative interviews with 18 PCPs and 29 adults 65 years or older prescribed opioids between September 15, 2022, and April 26, 2023, at a Boston-based academic medical center. The PCPs were asked about their experiences prescribing and deprescribing opioids to older adults. Patients were asked about their experiences using and discussing opioid medications with PCPs., Main Outcome and Measures: Shared and conflicting themes between patients and PCPs regarding perceptions of opioid prescribing and barriers to deprescribing., Results: In total, 18 PCPs (12 [67%] younger that 50 years; 10 [56%] female; and 14 [78%] based at an academic practice) and 29 patients (mean [SD] age, 72 [5] years; 19 [66%] female) participated. Participants conveyed that conversations between PCPs and patients on opioid use for chronic pain were typically challenging and that conversations regarding opioid risks and deprescribing were uncommon. Three common themes related to experiences with opioids for chronic pain emerged in both patient and PCP interviews: opioids were used as a last resort, opioids were used to improve function and quality of life, and trust was vital in a clinician-patient relationship. Patients and PCPs expressed conflicting views on risks of opioids, with patients focusing on addiction and PCPs focusing on adverse drug events. Both groups felt deprescribing conversations were often unsuccessful but had conflicting views on barriers to successful conversations. Patients felt deprescribing was often unnecessary unless an adverse event occurred, and many patients had prior negative experiences tapering. The PCPs described gaps in knowledge on how to taper, a lack of clinical access to monitor patients during tapering, and concerns about patient resistance., Conclusions and Relevance: In this qualitative study, PCPs and older adults receiving long-term opioid therapy viewed the use of opioids as a beneficial last resort for treating chronic pain but expressed dissonant views on the risks associated with opioids, which made deprescribing conversations challenging. Interventions, such as conversation aids, are needed to support collaborative discussion about deprescribing opioids.

Grifola frodosa polysaccharides, especially β-D-glucans, possess significant anti-tumor, antioxidant and immunostimulatory activities. However, the synthesis mechanism remains to be elucidated. A newly discovered glycosyltransferase UGT88A1 was found to extend glucan chains in vitro. However, the role of UGT88A1 in the growth and polysaccharide synthesis of G. frondosa in vivo remains unclear. In this study, the overexpression of UGT88A1 improved mycelial growth, increased polysaccharide production, and decreased cell wall pressure sensitivity. Biomass and polysaccharide production decreased in the silenced strain, and the pressure sensitivity of the cell wall increased. Overexpression and silencing of UGT88A1 both affected the monosaccharide composition and surface morphology of G. frondosa polysaccharides and influenced the antioxidant activity of polysaccharides from different strains. The messenger RNA expression of glucan synthase (GLS), UTP-glucose-1-phosphate uridylyltransferase (UGP), and UDP-xylose-4-epimerase (UXE) related to polysaccharide synthesis, and genes related to cell wall integrity increased in the overexpression strain. Overall, our study indicates that UGT88A1 plays an important role in the growth, stress, and polysaccharide synthesis of G. frondosa, providing a reference for exploring the pathway of polysaccharide synthesis and metabolic regulation. KEY POINTS: •UGT88A1 plays an important role in the growth, stress response, and polysaccharide synthesis in G. frondosa. •UGT88A1 affected the monosaccharide composition, surface morphology and antioxidant activity of G. frondosa polysaccharides. •UGT88A1 regulated the mRNA expression of genes related to polysaccharide synthesis and cell wall integrity., (© 2024. The Author(s).)

Immunotherapies targeting PD-1/PD-L1 are now widely used in the clinic to treat a variety of malignancies. While most of the research on T cell exhaustion and PD-1 blockade has been focused on conventional αβ T cells, the contribution of innate-like T cells such as γδ T cells to anti-PD-1/PD-L1 mediated therapy is limited. Here we show that tumor reactive γδ T cells respond to PD-1 blockade in a Merkel cell carcinoma (MCC) patient experiencing a complete response to therapy. We find clonally expanded γδ T cells in the blood and tumor after pembrolizumab treatment, and this Vγ2Vδ1 clonotype recognizes Merkel cancer cells in a TCR-dependent manner. Notably, the intra-tumoral γδ T cells in the MCC patient are characterized by higher expression of PD-1 and TIGIT, relative to conventional CD4 and CD8 T cells. Our results demonstrate that innate-like T cells could also contribute to an anti-tumor response after PD-1 blockade., (© 2024. The Author(s).)

Seven new species of the family Psychomyiidae Walker, 1852 are described and illustrated from China; they are Psychomyiashuni sp. nov. , Ps.mangshanensis sp. nov. , Ps.capricornis sp. nov. , Lypesagittalis sp. nov. , Paduniellafasciaria sp. nov. , Pa.sanyaensis sp. nov. , and Tinodesaviformis sp. nov. The genus Lype is reported for the first time from mainland China. In addition, four psychomyiids are found to be new to the Chinese caddis fauna: Psychomyiaindra Malicky & Chantaramongkol, 1993; Paduniellaandamanensis Malicky, 1979; Pa.dendrobia Malicky & Chantaramongkol, 1993; and Tinodesgapbona Johanson & Oláh, 2008. Moreover, Psychomyiapolyacantha Li, Qiu & Morse, 2021 is reviewed and synonymized with Psychomyiaimamiah Malicky, 2020., Competing Interests: The authors have declared that no competing interests exist., (Lang Peng, Zhen Deng, Yu-hua Zhang, Meng Wang, Chang-hai Sun, Bei-xin Wang.)

X-ray photon correlation spectroscopy (XPCS) holds strong promise for observing atomic-scale dynamics in materials, both at equilibrium and during non-equilibrium transitions. Here an in situ XPCS study of the relaxor ferroelectric PbMg 1/3 Nb 2/3 O 3 (PMN) is reported. A weak applied AC electric field generates strong response in the speckle of the diffuse scattering from the polar nanodomains, which is captured using the two-time correlation function. Correlated motions of the Bragg peak are also observed, which indicate dynamic tilting of the illuminated volume. This tilting quantitatively accounts for the observed two-time speckle correlations. The magnitude of the tilting would not be expected solely from the modest applied field, since PMN is an electrostrictive material with no linear strain response to the field. A model is developed based on non-uniform static charging of the illuminated surface spot by the incident micrometre-scale X-ray beam and the electrostrictive material response to the combination of static and dynamic fields. The model qualitatively explains the direction and magnitude of the observed tilting, and predicts that X-ray-induced piezoresponse could be an important factor in correctly interpreting results from XPCS and nanodiffraction studies of other insulating materials under applied AC field or varying X-ray illumination., (open access.)

Surface-enhanced Raman scattering (SERS) is widely used as a powerful analytical technology in cutting-edge areas such as food safety, biology, chemistry, and medical diagnosis, providing ultra-fast, ultra-sensitive, nondestructive characterization and achieving ultra-high detection sensitivity even down to the single-molecule level. Development of Raman spectroscopy is strongly dependent on high-performance SERS substrates, which have long evolved from the early days of rough metal electrodes to periodic nanopatterned arrays building on solid supporting substrates. For rigid SERS substrates, however, their applications are restricted by sophisticated pretreatments for detecting solid samples with non-planar surfaces. It is therefore essential to reassert the principles in constructing flexible SERS substrates. Herein, we comprehensively review the state-of-the-art in understanding, preparing and using flexible SERS. The basic mechanisms behind the flexible SERS are briefly outlined, typical design strategies are highlighted and diversified selection of materials in preparing flexible SERS substrates are reviewed. Then the recent achievements of various interdisciplinary applications based on flexible SERS substrates are summarized. Finally, the challenges and perspectives for future evolution of flexible SERS and their applications are demonstrated. We propose new research directions focused on stimulating the real potential of SERS as an advanced analytical technique for commercialization.

The hard-healing chronic wounds of diabetics are still one of the most intractable problems in clinical skin injury repair. Wound microenvironments directly affect wound healing speed, but conventional dressings exhibit limited efficacy in regulating the wound microenvironment and facilitating healing. To address this serious issue, we designed a thermo-sensitive drug-controlled hydrogel with wound self-adjusting effects, consisting of a sodium alginate (SA), Antheraeapernyi silk gland protein (ASGP) and poly(N-isopropylacrylamide) (PNIPAM) for a self-adjusting microenvironment, resulting in an intelligent releasing drug which promotes skin regeneration. PNIPAM has a benign temperature-sensitive effect. The contraction, drugs and water molecules expulsion of hydrogel were generated upon surpassing lower critical solution temperatures, which made the hydrogel system have smart drug release properties. The addition of ASGP further improves the biocompatibility and endows the thermo-sensitive drug-controlled hydrogel with adhesion. Additionally, in vitro assays demonstrate that the thermo-sensitive drug-controlled hydrogels have good biocompatibility, including the ability to promote the adhesion and proliferation of human skin fibroblast cells. This work proposes an approach for smart drug-controlled hydrogels with a thermo response to promote wound healing by self-adjusting the wound microenvironment.

A new tunable broadband terahertz metamaterial absorber has been designed based on patterned vanadium dioxide ( V O 2 ). The absorber consists of three simple layers, the top V O 2 pattern layer, the middle media layer, and the bottom metal layer. Based on phase transition properties of V O 2 , the designed device has excellent absorption modulation capability, achieving the functional transition from broadband absorption to near-perfect reflection. When V O 2 is in the metallic state, there are two absorption peaks observed at frequencies of 4.16 and 6.05 THz, exhibiting near-perfect absorption characteristics; the combination of these two absorption peaks gives rise to the broadband phenomenon and the absorption bandwidth, where the absorbance exceeds 90% and spans from 3.40 to 7.00 THz, with a corresponding relative absorption bandwidth of 69.23%. The impedance matching theory, near-field patterns, and surface current distributions are provided to analyze the causes of broadband absorption. Furthermore, the broadband absorption could be completely suppressed when V O 2 presents the dielectric phase, and its absorbance could be dynamically adjusted from 100% to less than 0.70%, thereby achieving near-perfect reflection. Owing to its symmetrical structure, it exhibits excellent performance in different polarization directions and at large incidence angles. Our proposed absorber may have a wide range of promising applications and can be applied in a variety of fields such as communications, imaging, sensing, and security detection.

Objective: To investigate the effect of Baicalin on the proliferation and pyroptosis of diffuse large B-cell lymphoma cell line DB and its mechanism., Methods: DB cells were treated with baicalin at different concentrations (0, 5, 10, 20, 40 μmol/L). Cell proliferation was detected by CCK-8 assay and half maximal inhibitory concentration (IC 50 ) was calculated. The morphology of pyroptosis was observed under an inverted microscope, the integrity of the cell membrane was verified by LDH content release assay, and the expressions of pyroptosis-related mRNA and protein (NLRP3, GSDMD, GSDME, N-GSDMD, N-GSDME) were detected by real-time fluorescence quantitative PCR and Western blot. In order to further clarify the relationship between baicalin-induced pyroptosis and ROS production in DB cells, DB cells were divided into control group, baicalin group, NAC group and NAC combined with baicalin group. DB cells in the NAC group were pretreated with ROS inhibitor N-acetylcysteine (NAC) 2 mmol/L for 2 h. Baicalin was added to the combined treatment group after pretreatment, and the content of reactive oxygen species (ROS) in the cells was detected by DCFH-DA method after 48 hours of culture., Results: Baicalin inhibited the proliferation of DB cells in a dose-dependent manner ( r =-0.99), and the IC 50 was 20.56 μmol/L at 48 h. The morphological changes of pyroptosis in DB cells were observed under inverted microscope. Compared with the control group, the release of LDH in the baicalin group was significantly increased ( P <0.01), indicating the loss of cell membrane integrity. Baicalin dose-dependently increased the expression levels of NLRP3, N-GSDMD, and N-GSDME mRNA and protein in the pyroptosis pathway ( P <0.05). Compared with the control group, the level of ROS in the baicalin group was significantly increased ( P <0.05), and the content of ROS in the NAC group was significantly decreased ( P <0.05). Compared with the NAC group, the content of ROS in the NAC + baicalin group was increased. Baicalin significantly attenuated the inhibitory effect of NAC on ROS production ( P <0.05). Similarly, Western blot results showed that compared with the control group, the expression levels of pyroptosis-related proteins was increased in the baicalin group ( P <0.05). NAC inhibited the expression of NLRP3 and reduced the cleavage of N-GSDMD and N-GSDME ( P <0.05). Compared with the NAC group, the NAC + baicalin group had significantly increased expression of pyroptosis-related proteins. These results indicate that baicalin can effectively induce pyroptosis in DB cells and reverse the inhibitory effect of NAC on ROS production., Conclusion: Baicalin can inhibit the proliferation of DLBCL cell line DB, and its mechanism may be through regulating ROS production to affect the pyroptosis pathway.

Multi-band electromagnetically induced transparency (EIT) effects have attracted widespread attention due to their great application prospects. However, their realization is mainly based on the coupling of multiple sub-resonators that typically exceed the number of transparency peaks, resulting in complex structural designs and cumbersome preparation procedures. This paper reports a simple design of a terahertz metamaterial that can produce the triple-band EIT effect using two "big-bright" mode coupling of two sub-resonators. The design adopts the classical two-layer structure. A U-shaped split-ring resonator and a fork-shaped resonator form a periodic array on the surface of the flexible organic polymer material. Three transparency peaks around 0.59 THz, 1.07 THz, and 1.34 THz are experimentally realized, and their formation mechanisms are explored. Furthermore, the triple-band EIT metamaterial was prepared by the photolithography technology and characterized by terahertz time-domain spectroscopy. Theoretical simulation results agree well with experimental results. Sensing characteristics and slow light effects of the terahertz metamaterial are further discussed experimentally. The proposed triple-band EIT metamaterial having excellent properties, including thin size, good flexibility, simple and compact structure, and high sensing sensitivity, could provide guidance for the subsequent design and implementation of multifunctional multi-band EIT metamaterials.

The application of new-generation information technologies such as big data, the internet of things(IoT), and cloud computing in the traditional Chinese medicine(TCM)manufacturing industry is gradually deepening, driving the intelligent transformation and upgrading of the TCM industry. At the current stage, there are challenges in understanding the extraction process and its mechanisms in TCM. Online detection technology faces difficulties in making breakthroughs, and data throughout the entire production process is scattered, lacking valuable mining and utilization, which significantly hinders the intelligent upgrading of the TCM industry. Applying data-driven technologies in the process of TCM extraction can enhance the understanding of the extraction process, achieve precise control, and effectively improve the quality of TCM products. This article analyzed the technological bottlenecks in the production process of TCM extraction, summarized commonly used data-driven algorithms in the research and production control of extraction processes, and reviewed the progress in the application of data-driven technologies in the following five aspects: mechanism analysis of the extraction process, process development and optimization, online detection, process control, and production management. This article is expected to provide references for optimizing the extraction process and intelligent production of TCM.

Purpose: Non-inflamed (cold) tumors such as leiomyosarcoma do not benefit from immune checkpoint blockade (ICB) monotherapy. Combining ICB with angiogenesis or PARP inhibitors may increase tumor immunogenicity by altering the immune cell composition of the tumor microenvironment (TME). The DAPPER phase II study evaluated the safety, immunologic, and clinical activity of ICB-based combinations in pretreated patients with leiomyosarcoma., Patients and Methods: Patients were randomized to receive durvalumab 1,500 mg IV every 4 weeks with either olaparib 300 mg twice a day orally (Arm A) or cediranib 20 mg every day orally 5 days/week (Arm B) until unacceptable toxicity or disease progression. Paired tumor biopsies, serial radiologic assessments and stool collections were performed. Primary endpoints were safety and immune cell changes in the TME. Objective responses and survival were correlated with transcriptomic, radiomic, and microbiome parameters., Results: Among 30 heavily pretreated patients (15 on each arm), grade ≥ 3 toxicity occurred in 3 (20%) and 2 (13%) on Arms A and B, respectively. On Arm A, 1 patient achieved partial response (PR) with increase in CD8 T cells and macrophages in the TME during treatment, while 4 had stable disease (SD) ≥ 6 months. No patients on Arm B achieved PR or SD ≥ 6 months. Transcriptome analysis showed that baseline M1-macrophage and B-cell activity were associated with overall survival., Conclusions: Durvalumab plus olaparib increased immune cell infiltration of TME with clinical benefit in some patients with leiomyosarcoma. Baseline M1-macrophage and B-cell activity may identify patients with leiomyosarcoma with favorable outcomes on immunotherapy and should be further evaluated., (©2023 American Association for Cancer Research.)

Purpose: To investigate the current status of oral health literacy among adult orthodontic patients and analyze its influencing factors., Methods: Totally 163 adult orthodontic patients were recruited by convenience sampling method from November 2021 to February 2022 at the Department of Oral and Craniomaxillofacial Surgery, Center of Craniofacial Orthodontics in Shanghai Ninth People's Hospital. General information questionnaire, Chinese version of Health Literacy in Dentistry (HeLD-14), Chinese version of Self-Efficacy Scale for Self-care (SESS) and Social Support Rating Scale (SSRS) were applied. SPSS 21.0 software package was used for data analysis., Results: The mean score of oral health literacy in adult orthodontic patients was (48.74±5.54), and the lowest score were obtained in concern (6.80±1.19) and support (6.40±1.59) dimensions. Multiple stepwise regression analysis showed that adult orthodontic patients' consultation self-efficacy, social support utilization, family or friends' orthodontic history and objective support were the influencing factors of oral health literacy., Conclusions: The oral health literacy in adult orthodontic patients is at a middle to high level, but concern and support literacy need to be improved. Strengthening consultation self-efficacy, objective support and utilization of social support can improve adult orthodontic patients' oral health literacy. Attention should be paid to patients who have no relatives or friends with history of orthodontic treatment.

It is well known that vitamin D is engaged in calcium and phosphorus metabolism. However, vitamin D also plays an important role in other aspects over the past decades, such as immune response. Vitamin D has thus aroused the interest of the scientific community, especially the field of dermatology. The major source of vitamin D comes from the exposure of the skin to ultraviolet B. In turn, vitamin D regulates the proliferation and differentiation of keratinocytes, prevents opportunistic infection, and regulates the inflammatory response and immune response of the skin. Acne, psoriasis, atopic dermatitis, and other inflammatory skin diseases have been found to have a certain relationship with vitamin D. This article review the correlation between vitamin D and inflammatory skin diseases.

Activation of mixed lineage kinase 3 (MLK3) by phosphorylation at Thr277/Ser281 stimulates downstream apoptotic pathways and ultimately leads to cell injury. MLK3 is reported to localize to both the cytoplasm and nucleus in human ovarian cancer cells and immortalized ovarian epithelial cells (T80 and T90 cells), and phosphorylation at Thr477 is required for the cytoplasmic retention of MLK3 in T80 cells. However, the subcellular distribution of MLK3 in other cell types has rarely been reported, and whether phosphorylation of MLK3 at Thr277/Ser281 affects its subcellular distribution is unknown. Here, our bioinformatics analysis predicted that MLK3 was mainly distributed in the cytoplasm and nucleus. In the human HEK293T embryonic kidney cell line and murine HT22 hippocampal neuronal cell line, endogenous MLK3 was more abundant in the cytoplasm and less abundant in the nucleus. In addition, overexpressed Myc-tagged MLK3 and EGFP-tagged MLK3 were also observed to localize mainly to the cytoplasm. MLK3 that was activated by phosphorylation at Thr277/Ser281 was mainly distributed in the cytoplasm, and phosphorylation deficient (T277A/S281A) and mimic (T277E/S281E) mutants both showed distributions similar to that of wild type (wt) MLK3, further proving that phosphorylation at Thr277/Ser281 was not involved in regulating MLK3 subcellular localization. In HEK293T cells, H 2 O 2 stimulation accelerated MLK3 phosphorylation (activation), and this phosphorylation was reduced by the antioxidant N-acetylcysteine in a dose-dependent manner. Overexpressing wt MLK3 promoted the production of intracellular reactive oxygen species and increased cell apoptosis, both of which were enhanced by the phosphorylation-mimic (T277E/S281E) MLK3 variant but not by the phosphorylation-deficient (T277A/S281A) MLK3 variant. These findings provided additional evidence for the cytoplasmic and nuclear distribution of MLK3 in HEK293T cells or HT22 cells and revealed the pivotal role of MLK3 in the positive feedback loop of oxidative stress injury., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Understanding where species occur using species distribution models has become fundamental to ecology. Although much attention has been paid to invasive species, questions about climate change related range shifts of widespread insect pests remain unanswered. Here, we incorporated bioclimatic factors and host plant availability into CLIMEX models to predict distributions under future climate scenarios of major cereal pests of the Sitobion grain aphid complex (Sitobion avenae, S. miscanthi, and S. akebiae). Additionally, we incorporated the application of irrigation in our models to explore the relevance of a frequently used management practice that may interact with effects of climate change of the pest distributions., Results: Our models predicted that the area potentially at high risk of outbreaks of the Sitobion grain aphid complex would increase from 41.3% to 53.3% of the global land mass. This expansion was underlined by regional shifts in both directions: expansion of risk areas in North America, Europe, most of Asia, and Oceania, and contraction of risk areas in South America, Africa, and Australia. In addition, we found that host plant availability limited the potential distribution of pests, while the application of irrigation expanded it., Conclusion: Our study provides insights into potential risk areas of insect pests and how climate, host plant availability, and irrigation affect the occurrence of the Sitobion grain aphid complex. Our results thereby support agricultural policy makers, farmers, and other stakeholders in their development and application of management practices aimed at maximizing crop yields and minimizing economic losses. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Immunotherapeutic strategies aimed at enhancing tumor cell killing by tumor-specific T cells hold great potential for reducing tumor burden and prolonging survival of cancer patients. Although many potential tumor antigens have been described, identifying relevant targets when designing anti-cancer vaccines or targeted cell therapies remains a challenge. To identify novel, potentially immunogenic candidate tumor antigens, we performed integrated tumor transcriptomic, seromic, and proteomic analyses of high grade serous ovarian cancer (HGSC) patient tumor samples. We identified tumor neo-antigens and over-expressed antigens using whole exome and RNA sequencing and examined these in relation to patient-matched auto-antibody repertoires. Focusing on MHC class I epitopes recognized by CD8 +  T cells, HLA-binding epitopes were identified or predicted from the highly expressed, mutated, or auto-antibody target antigen, or MHC-associated peptides (MAPs). Recognition of candidate antigenic peptides was assessed within the tumor-infiltrating T lymphocyte (TIL) population expanded from each patient. Known tumor-associated antigens (TAA) and cancer/testis antigens (CTA) were commonly found in the auto-antibody and MAP repertoires and CD8 +  TILs recognizing epitopes from these antigens were detected, although neither expression level nor the presence of auto-antibodies correlated with TIL recognition. Auto-antibodies against tumor-mutated antigens were found in most patients, however, no TIL recognition of the highest predicted affinity neo-epitopes was detected. Using high expression level, auto-antibody recognition, and epitope prediction algorithms, we identified epitopes in 5 novel antigens (MOB1A, SOCS3, TUBB, PRKAR1A, CCDC6) recognized by HGSC patient TILs. Furthermore, selection of epitopes from the MAP repertoire identified 5 additional targets commonly recognized by multiple patient TILs. We find that the repertoire of TIL specificities includes recognition of highly expressed and immunogenic self-antigens that are processed and presented by tumors. These results indicate an ongoing autoimmune response against a range of self-antigens targeted by HGSC TILs., (© 2023. The Author(s).)

A bifunctional terahertz meta-material absorber with three layers is designed. The surface of the bifunctional meta-material absorber is a periodically patterned array composed of hybrid structures of vanadium dioxide (VO 2 ) and metallic resonators; the middle layer is a nondestructive TOPAS film, and the bottom layer is a continuous metallic plane. Utilizing the phase-transition property of VO 2 , the responses of the meta-material absorber could be dynamically switched between triple-band absorption and ultra-broadband absorption. When VO 2 is in the metallic state, an ultra-broadband absorption covering the bandwidth of 6.62 THz is achieved over the range from 4.71 THz to 11.33 THz. When VO 2 is in the di-electric state, three absorption peaks resonated at 10.57 THz, 12.68 THz, and 13.91 THz. The physical mechanisms of the bifunctional meta-material absorber were explored by analyzing their near-field distributions. The effects of varying structural parameters on triple-band and ultra-broadband absorption were investigated. It is revealed that by optimizing the structure parameters, the number of absorption peaks could be increased for a certain sacrifice of absorption bandwidth. FDTD Solutions and CST Microwave Studio were used to simulate the data of the absorber, and similar results were obtained.

Although transition metal selenides are considered to be extremely promising anode materials for lithium-ion batteries (LIBs), severe volume changes and low electronic conductivity are their huge and unavoidable challenges. To solve these problems, CoSe nanoparticles in-situ grown on the inner surface of every macropore of 3D honeycomb C is successfully synthesized by three simple steps: dense assembling of polystyrene spheres, calcination and gaseous selenylation. The sizes of CoSe and honeycomb pores are 10-15 nm and 190 nm, respectively. The content of CoSe is 72 wt%. This unique architecture guarantees high electrochemical activity, rapid reaction kinetics and excellent structural stability of CoSe, as identified by cycling and rate performance measurements, various electrochemical kinetics analyses and ex-situ characterization of the cycled electrode material. As a result, the CoSe@honeycomb C anode exhibits extraordinary cycling performance (823.5 mAh g -1 after 200 cycles at 0.5 A g -1 , 610.1 mAh g -1 after 250 cycles at 2 A g -1 , 247 mAh g -1 after 1500 cycles at 5 A g -1 ) and exceptional rate capability (261.9 mAh g -1 at 10 A g -1 , 1491.4 mAh g -1 at 0.1 A g -1 ), demonstrating that it is a potential anode material for high-performance LIBs., 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 Inc. All rights reserved.)

Phyllostachys incarnata Wen, 1982 is one of the important material and edible bamboo specie of high quality in China. We reported the complete chloroplast(cp) genome of P. incarnata in this study. The cp genome of P. incarnata (GenBank accession number: OL457160) was a typical tetrad structure with a full length of 139,689 bp, comprising a pair of inverted repeated (IR) regions (21,798 bp) separated by a large single-copy (LSC) region (83,221 bp) and a small single-copy (SSC) region (12,872 bp). And the cp genome contained 136 genes, including 90 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. Phylogenetic analysis based on 19 cp genomes suggested that P. incarnata was relatively close to P. glauca among the species analyzed., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

We design a four-band narrow-band near-perfect absorber based on bulk Dirac semimetal (BDS) metamaterial in the terahertz region. The absorber has a top-to-bottom three-layer structure of a BDS layer, an insulating dielectric slab, and a gold layer. The BDS is flexible and tunable, allowing the Fermi energy level to be adjusted by changing the applied bias voltage, thus changing the absorption characteristics of the absorber. We use the time-domain finite-difference method to simulate the absorption characteristics of the absorber, which could achieve four discrete near-perfect absorption peaks at 0.98 THz, 1.70 THz, 2.02 THz, and 2.36 THz. The absorber is polarization sensitive, and the conversion between four-band absorption and three-band absorption is achieved by changing the incident polarization angle. We also change the structure of the absorber to study the absorption characteristics and break the structural symmetry to achieve a larger number of absorption peaks. Besides, the sensing performance of four-band narrow-band absorption is analyzed, and the maximum sensitivity of the absorber is 112.78 GHz/RIU. The device should have vast application prospects for bio-detection and high-sensitivity biosensing detection.

Lead hafnate (PbHfO 3 ) has attracted a lot of renewed interest due to its potential as antiferroelectric (AFE) material for energy storage. However, its room temperature (RT) energy-storage performance has not been well established and no reports on the energy-storage feature of its high-temperature intermediate phase (IM) are available. In this work, high-quality PbHfO 3 ceramics were prepared via the solid-state synthesis route. Based on high-temperature X-ray diffraction data, the IM of PbHfO 3 was found to be orthorhombic, Imma space group, with antiparallel alignment of Pb 2+ ions along the [001] cubic directions. The polarization-electric field (P-E) relation of PbHfO 3 is displayed at RT as well as in the temperature range of the IM. A typical AFE loop revealed an optimal recoverable energy-storage density ( W rec ) of 2.7 J/cm 3 , which is 286% higher than the reported data with an efficiency (η) of 65% at 235 kV/cm at RT. A relatively high W rec value of 0.7 J/cm 3 was found at 190 °C with an η of 89% at 65 kV/cm. These results demonstrate that PbHfO 3 is a prototypical AFE from RT up to 200 °C, making it a suitable material for energy-storage applications in a wide temperature range.

Objective: To investigate the effect of baicalin on the growth of extranodal NK/T cell lymphoma (ENKTCL) cells and its related mechanism., Methods: Normal NK cells and human ENKTCL cells lines SNK-6 and YTS were cultured, then SNK-6 and YTS cells were treated with 5, 10, 20 μmol/L baicalin and set control. Cell proliferation and apoptosis was detected by Edu method and FCM method, respectively, and expressions of BCL-2, Bax, FOXO3 and CCL22 proteins were detected by Western blot. Interference plasmids were designed and synthesized. FOXO3 siRNA interference plasmids and CCL22 pcDNA overexpression plasmids were transfected with PEI transfection reagent. Furthermore, animal models were established for validation., Results: In control group and 5, 10, 20 μmol/L baicalin group, the proliferation rate of SNK-6 cells was (56.17±2.96)%, (51.92±4.63)%, (36.42±1.58)%, and (14.60±2.81)%, respectively, while that of YTS cells was (58.85±2.98)%, (51.38±1.32)%, (34.75±1.09)%, and (15.45±1.10)%, respectively. In control group and 5, 10, 20 μmol/L baicalin group, the apoptosis rate of SNK-6 cells was (5.93±0.74)%, (11.78±0.34)%, (28.46±0.44)%, and (32.40±0.37)%, respectively, while that of YTS cells was (7.93±0.69)%, (16.29±1.35)%, (33.91±1.56)%, and (36.27±1.06)%, respectively. Compared with control group, the expression of BCL-2 protein both in SNK-6 and YTS cells decreased significantly ( P <0.001), and the expression of Bax protein increased in SNK-6 cells only when the concentration of baicalin was 20 μmol/L ( P <0.001), while that in YTS cells increased in all three concentrations(5, 10, 20 μmol/L) of baicalin ( P <0.001). The expression of FOXO3 protein decreased while CCL22 protein increased in ENKTCL cell lines compared with human NK cells ( P <0.001), but the expression of FOXO3 protein increased ( P <0.01) and CCL22 protein decreased after baicalin treatment ( P <0.001). Animal experiments showed that baicalin treatment could inhibit tumor growth. The expression of CCL22 protein in ENKTCL tissue of nude mice treated with baicalin decreased compared with control group ( P <0.01), while the FOXO3 protein increased ( P <0.05). In addition, FOXO3 silencing resulted in the decrease of FOXO3 protein expression and increase of CCL22 protein expression ( P <0.01, P <0.001)., Conclusion: Baicalin can inhibit proliferation and promote apoptosis of ENKTCL cell lines SNK-6 and YTS, up-regulate the expression of Bax protein, down-regulate the expression of BCL-2 protein, and down-regulate the expression of CCL22 protein mediated by FOXO3 . Animal experiment shown that the baicalin can inhibit tumor growth. Baicalin can inhibit the growth and induce apoptosis of ENKTCL cells through FOXO3 / CCL22 signaling pathway.

Background: The intestinal microbiome has been associated with response to immune checkpoint inhibitors (ICIs) in humans and causally implicated in ICI responsiveness in animal models. Two recent human trials demonstrated that fecal microbiota transplant (FMT) from ICI responders can rescue ICI responses in refractory melanoma, but FMT has specific limitations to scaled use., Patients and Methods: We conducted an early-phase clinical trial of a cultivated, orally delivered 30-species microbial consortium (Microbial Ecosystem Therapeutic 4, MET4) designed for co-administration with ICIs as an alternative to FMT and assessed safety, tolerability and ecological responses in patients with advanced solid tumors., Results: The trial achieved its primary safety and tolerability outcomes. There were no statistically significant differences in the primary ecological outcomes; however, differences in MET4 species relative abundance were evident after randomization that varied by patient and species. Increases in the relative abundance of several MET4 taxa, including Enterococcus and Bifidobacterium, taxa previously associated with ICI responsiveness, were observed and MET4 engraftment was associated with decreases in plasma and stool primary bile acids., Conclusions: This trial is the first report of the use of a microbial consortium as an alternative to FMT in advanced cancer patients receiving ICI and the results justify the further development of microbial consortia as a therapeutic co-intervention for ICI treatment in cancer., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Wallis dynamic stabilization system is a surgical approach in the non-fusion technique of lumbar spine, consisting of interspinous blockers and dacron artificial ligaments that provide stability to the spine while maintaining a degree of motion in the affected segment. Recent studies have demonstrated the significant benefits of Wallis dynamic stabilization system in treating lumbar degenerative diseases. It not only improves clinical symptoms, but also effectively delays complications such as adjacent segmental degeneration. This paper aims to review the literature related to the Wallis dynamic stabilization system and degenerative diseases of the lumbar spine to describe the long-term prognostic effect of this system in the treatment of such diseases. This review provides a theoretical basis and reference for selecting surgical methods to treat degenerative diseases of the lumbar spine.

Integrated cross-scale milli/microlenses offer irreplaceable functions in modern integrated optics with the advantage of reducing the size of the optical system to millimeters or microns. However, the technologies for fabricating millimeter-scale lenses and microlenses are always incompatible, which makes the successful fabrication of cross-scale milli/microlenses with a controlled morphology challenging. Here, ion beam etching is proposed as a means to fabricate smooth millimeter-scale lenses on various hard materials. In addition, by combining femtosecond laser modification and ion beam etching, an integrated cross-scale concave milli/microlens (27,000 microlenses on a lens with a diameter of 2.5 mm) is demonstrated on fused silica, and can be used as the template for a compound eye. The results provide a new, to the best of our knowledge, route for the flexible fabrication of cross-scale optical components for modern integrated optical systems.