Immune-stimulating antibody drug conjugate (ISAC) can not only effectively solve the defects of stimulator of interferon genes (STING) agonists by coupling antibodies with STING agonists through the targeting of antibodies, but also play a synergistic role with antibodies to further improve the efficacy of STING agonists. This review first provides a concise overview of the current research landscape of ISACs and STING agonists, systematically elaborates on evolving trends in STING agonist development, and subsequently summarizes the mechanistic advances in STING ISAC research. Special emphasis is placed on representative STING ISAC candidates in preclinical/clinical development. Finally, the future directions of STING ISACs are critically discussed with perspectives and recommendations, aiming to provide theoretical insights and practical guidance for future investigations.

Stria vascularis（SV）, located in the lateral wall of the cochlea, is a highly vascularized tissue that plays a crucial role in maintaining the homeostasis of endolymph and normal auditory function, with its core function relying on the transporter system distributed within it. These transporters in the SV precisely mediate the transport of ions, nutrients, and metabolites, constituting the cornerstone of the homeostasis of endolymph. Abnormal expression or dysfunction of transporters in the SV can lead to an imbalance in the inner ear microenvironment, which can lead to hearing loss. However, the effects of transporters in SV on hearing loss have not been fully clarified. In this paper, the function and distribution of different types of transporters in SV and their relationship with hearing loss are reviewed, providing a new perspective and prospect for exploring the molecular basis of hearing loss and targeted therapies of transporters in the future.

Objective:To investigate the clinical significance of vertebral body partition in the unipedicular percutaneous vertebroplasty (PVP) for osteoporotic vertebral fractures.Methods:From July 2019 to October 2021, 89 patients with osteoporotic vertebral fracture were treated by unipedicular PVP at Department of Spinal Surgery, Zhengzhou Orthopaedic Hospital. They were 37 males and 52 females, with a mean age of (70.5±4.8) years (from 60 to 80 years). According to the vertebral body partition, the patients were divided into group a (32 cases), group b (20 cases), group c (21 cases), group d (11 cases), group e (0 case) and group f (5 cases). The therapeutic effects were evaluated by comparing the improvement rates of visual analogue scale (VAS) and Oswestry disability index (ODI) between preoperation and postoperative 1-day among all partition groups. The imaging efficacy was evaluated by comparing the proportions of bone cement diffusion area in the posteroanterior and lateral DR films and the leakage of bone cement among all partition groups.Results:The improvement rates of VAS score between preoperation and postoperation: group a [77.8 (75.0, 82.5) %] > group b [71.4 (71.4, 71.4) %] > group c [66.7 (66.7, 66.7) %] > group d [60.0 (60.0, 62.5) %] > group f [57.1 (50.0, 57.1)%], showing a statistically significant difference between any 2 groups ( P<0.001). The improvement rates of ODI score: group a (58.0%±4.2%) > group b (47.5%±2.5%) > group c (42.9%±2.9%) > group d (39.6%±3.2%) > group f (34.2%±8.4%), showing a statistically significant difference between any 2 groups ( P<0.001). The proportions of bone cement diffusion area: group a (76.9%±3.5%) > group b (71.3%±3.1%) > group c (66.1%±3.6%) > group d (60.2%±2.6%) > group f (54.0%±4.2%), showing a statistically significant difference between any 2 groups ( P<0.001). Bone cement leakage occurred in 7 cases, including 3 ones of anterior vertebral leakage (1 case in group a and 2 cases in group b), and 4 ones of leakage into the paravertebral venous plexus (2 cases in group c and 2 cases in group d). There was no intraspinal leakage, or symptoms of nerve compression or lesion. Conclusion:In the unipedicular PVP for osteoporotic vertebral fractures, our vertebral body partition can guide puncturing for bone cement injection because it indicates the optimal and the risky partitions.

Objective:To explore an assay that can concisely, rapidly, and accurately quantify the amount of chimeric antigen receptor (CAR)-T cells in the bone marrow or peripheral blood of patients after CAR-T cell immunotherapy by morphological analysis and flow cytometry assay, providing timely and accurate feedback for clinical treatment.Methods:We analyzed the CAR-T cell detection results in peripheral blood and bone marrow of 256 patients who received CAR-T cell immunotherapy in the Department of Hematology, Affiliated Hospital of Xuzhou Medical University from August 2016 to August 2021. All 256 patients survived more than one month after CAR-T cell infusion. Among them, there were 118 patients with multiple myeloma, 68 patients with acute lymphoblastic leukemia, and 70 patients with lymphoma. The morphological characteristics, positive rate and detection rate of CAR-T cell in peripheral blood and bone marrow were analyzed by morphological methods. The positive rate and detection rate of CAR-T in peripheral blood and bone marrow were analyzed by flow cytometry protein L detection. χ 2 test was used to comprehensively analyze the difference between the detection rate of the combined analysis of the two methods and the detection rate of the single method. Results:CAR-T cells have significant morphological characteristics, and there are obvious morphological differences from normal lymphocytes. The detection rates of CAR-T cells in peripheral blood or bone marrow by morphological methods and flow cytometry were 88.28%(226/256) and 79.29% (203/256), respectively. When the two methods were combined, the detection rate of CAR-T cells can reach 99.22%, with statistically significant difference comparing to that of single method( P<0.05). Through the analysis of the detection results of peripheral blood at different time points, it was found that the average detection rates of morphology and flow cytometry in 118 patients with multiple myeloma were 9.50% and 10.23% on the 7th day, and 13.50% and 15.19% respectively on the 15th day. On the 21st day, the average detection rates of morphology and flow cytometry were 8.00% and 10.07%, respectively. The average detection rates of morphology and flow cytometry in 68 patients with acute lymphoblastic leukemia were 12.00% and 11.22% on the 7th day, and 21.00% and 23.10% respectively on the 15th day. On the 21st day, the average detection rates of morphology and flow cytometry were 13.50% and 10.91%, respectively. The average detection rates of morphology and flow cytometry in 70 lymphoma patients were 7.50% and 10.35% on the 7th day, and 9.00% and 10.35% respectively on the 15th day. The average detection rates of morphology and flow cytometry at 21 days were 6.50% and 5.69%, respectively. The number of CAR-T cells in samples from patients with different diseases reached a peak around the 15th day. Conclusion:The detection rate of CAR-T cells from peripheral blood or bone marrow was significantly higher with the combination of the 2 methods compared to the single method.

The importance of structural variants(SVs)for human phenotypes and diseases is now recognized.Although a variety of SV detection platforms and strategies that vary in sensitivity and specificity have been developed,few benchmarking procedures are available to confidently assess their performances in biological and clinical research.To facilitate the validation and application of these SV detection approaches,we established an Asian reference material by characterizing the genome of an Epstein-Barr virus(EBV)-immortalized B lymphocyte line along with identified benchmark regions and high-confidence SV calls.We established a high-confidence SV callset with 8938 SVs by integrating four alignment-based SV callers,including 109x Pacific Biosciences(PacBio)continuous long reads(CLRs),22 x PacBio circular consensus sequencing(CCS)reads,104x Oxford Nanopore Technologies(ONT)long reads,and 114×Bionano optical mapping plat-form,and one de novo assembly-based SV caller using CCS reads.A total of 544 randomly selected SVs were validated by PCR amplification and Sanger sequencing,demonstrating the robustness of our SV calls.Combining trio-binning-based haplotype assemblies,we established an SV benchmark for identifying false negatives and false positives by constructing the continuous high-confidence regions(CHCRs),which covered 1.46 gigabase pairs(Gb)and 6882 SVs supported by at least one diploid haplotype assembly.Establishing high-confidence SV calls for a benchmark sample that has been characterized by multiple technologies provides a valuable resource for investigating SVs in human biology,disease,and clinical research.

Tung tree (Vernicia fordii) is an economically important woody oil plant that produces tung oil rich in eleostearic acid. Here, we report a high-quality chromosome-scale genome sequence of tung tree. The genome sequence was assembled by combining Illumina short reads, Pacific Bio-sciences single-molecule real-time long reads, and Hi-C sequencing data. The size of tung tree gen-ome is 1.12 Gb, with 28,422 predicted genes and over 73％ repeat sequences. The V. fordii underwent an ancient genome triplication event shared by core eudicots but no further whole-genome duplication in the subsequent ca. 34.55 million years of evolutionary history of the tung tree lineage. Insertion time analysis revealed that repeat-driven genome expansion might have arisen as a result of long-standing long terminal repeat retrotransposon bursts and lack of efficient DNA deletion mechanisms. The genome harbors 88 resistance genes encoding nucleotide-binding sites;17 of these genes may be involved in early-infection stage of Fusarium wilt resistance. Further, 651 oil-related genes were identified, 88 of which are predicted to be directly involved in tung oil biosynthesis. Relatively few phosphoenolpyruvate carboxykinase genes, and synergistic effectsbetween transcription factors and oil biosynthesis-related genes might contribute to the high oil content of tung seed. The tung tree genome constitutes a valuable resource for understanding genome evolution, as well as for molecular breeding and genetic improvements for oil production.

Objective To explore relationship of the anesthetic risks and intraoperative complications.Methods Preoperative anesthetic risks were assessed with Hussman's method from May 2015 to May 2016 in 2 494 surgical patients, including 1 462 males and 1 032 females.Intraoperative data and complications were tracked and recorded.Results Three hundred and thirty-six intraoperative complications occurred, accounting for 13.47% of total patients.The cardiovascular complications were a major intraoperative complications, accounting for 80.7%.2 494 patients were graded respectively into risk grade 1 with 1 540 (61.75%), grade 2 with 660 (26.46%), grade 3 with 202 (8.10%), grade 4 with 80 (3.21%) and grade 5 with 12 (0.48%).The incidence of complications were 112 (7.28%), 82 (12.42%), 82 (40.59%), 50 (62.50%) and 10 (83.33%) respectively.The sensitivity of prediction was 33.33%, 24.40%, 24.40%, 14.88% and 2.78%;the specificity 33.76%, 73.26%, 94.44%, 98.61% and 99.91%;and the accuracy 33.76%, 66.64%, 85.01%, 87.33% and 86.85%, respectively, in patients with risk grade 1, 2, 3, 4 and 5.Conclusion Hussman's method of anesthetic risks well predicts the intraoperative complications.

DNA Repair Enzymes ; Humans ; Phosphoric Monoester Hydrolases ; Precursor Cell Lymphoblastic Leukemia-Lymphoma

OBJECTIVETo investigate the sensitivity of imatinib (IM) on Sup-B15 Ph+ acute lmphoblastic leukemia (ALL) cells indused by stromal cells OP9, and to further explore its mechanism.

METHODSThe study is divided into two group, Sup-B15 cells group and co-cultured with OP9 cells group (Sup-B15/OP9 group). The inhibitory effects of IM on leukemia cells were measured by CCK-8 test, and the apoptosis by Annexin Ⅴ/7-AAD dyeing and the percentage of CD 34+CD38- leukemia cells were determined by flow cytometry. ALDH1, CD144, and β-catenin mRNA were detected by real-time RT-PCR, protein levels by Western blot. Inmunoprecipitation was used to detect the level of β-catenin connected to CD144.

RESULTSIM presented inhibitory effects on Sup-B15 and Sup-B15/OP9 cells at multiple concentrations from 10 μmol/L to 45 μmol/L. The IC50 of IM on Sup-B15/OP and Sup-B15 cells were 35.8 μmol/L and 6.3 μmol/L, respectively (P<0.05). After 24 h of 30 μmol/L IM treatment, the percentages of apoptosis cells in Sup-B15/OP9 and Sup-B 15 cell were (14.24 ± 2.11)% and (3.45 ± 0.68)%, respectively (P<0.05). The percentage of CD34+CD38- cells in Sup-B15/OP9 group was significantly higher than that in Sup-B15 group [(3.42 ± 0.28)% vs (0.16 ± 0.15)%, P<0.05]. As compared to Sup-B15 cells, the transcription of ALDH1 in Sup-B15/OP9 group was remarkably upregulated (0.097 ± 0.012 vs 0.046 ± 0.010, P<0.05), and the CD133 protein level was also upregulated in Sup-B15/OP9 group. The transcription of CD144 in Sup-B15/OP9 group was remarkably upregulated compared with Sup-B15 group (0.103 ± 0.015 vs 0.010±0.003, P<0.05), as well as the CD144 protein. β-catenin mRNA transcription has no obvious changes between Sup-B15 group and Sup-B15/OP9 group (P>0.05), while the whole β-catenin protein and the cell nucleus β-catenin significantly increased, as well as the β-catenin protein combined with CD144.

CONCLUSIONCo-cultured with OP9 cells, Sup-B15 cells show less sensitivity to imatinib. The raising activity of CD144 and CD144/β-catenin signaling may work in this procession.