Intelligent perceptual textiles based on ionic-conductive and strong silk fibers.

Endowing textiles with perceptual function, similar to human skin, is crucial for the development of next-generation smart wearables. To date, the creation of perceptual textiles capable of sensing potential dangers and accurately pinpointing finger touch remains elusive. In this study, we present the design and fabrication of intelligent perceptual textiles capable of electrically responding to external dangers and precisely detecting human touch, based on conductive silk fibroin-based ionic hydrogel (SIH) fibers. These fibers possess excellent fracture strength (55 MPa), extensibility (530%), stable and good conductivity (0.45 S·m-1) due to oriented structures and ionic incorporation. We fabricated SIH fiber-based protective textiles that can respond to fire, water, and sharp objects, protecting robots from potential injuries. Additionally, we designed perceptual textiles that can specifically pinpoint finger touch, serving as convenient human-machine interfaces. Our work sheds new light on the design of next-generation smart wearables and the reshaping of human-machine interfaces.

Effect of tannic/gallic acid-iron dyeing treatment on surface color and light fastness of bamboo veneer.

Currently, the quest for bamboo materials with high color fastness, rich colors and environmental friendliness is rapidly rising due to its potential applications in construction, furniture and decoration. However, finding an easy-to-operate and environmentally friendly dye for bamboo is a necessary task because of the difficulty in treating the dyeing waste liquid of acid dyes and the complexity of the production process of reactive dyes.Five formulations involving metal polyphenol complexes were employed to straightforwardly produce eco-friendly dyed bamboo and the impact of various formulations on the light aging resistance of the dyed veneers was examined. The results indicated that the light resistance of bamboo veneer dyed with the solution containing only FeSO4·7H2O and tannic acid reached level 4, surpassing the undyed bamboo veneer by three levels. The mechanism of enhanced lightfastness of dyed bamboo veneer was elucidated by XPS analysis. The polyphenol iron complex serves a dual purpose: it absorbs ultraviolet rays and scavenges free radicals within the system. Additionally, it reduced the oxidation of phenolics in the substrate, transforming them into dark-colored quinone structures. This process enhanced the light-aging resistance of the finishing materials. Therefore, this work provides a simple and environmentally friendly method for changing the color of bamboo and provides a new idea for the selection of dyes for bamboo dyeing in actual production.

Three New Species of Russulaceae (Russulales, Basidiomycota) from Southern China.

The characterization of natural fungal diversity impacts our understanding of ecological and evolutionary processes and can lead to novel bioproduct discovery. Russula and Lactarius, both in the order Russulales, represent two large genera of ectomycorrhizal fungi that include edible as well as toxic varieties. Based on morphological and phylogenetic analyses, including nucleotide sequences of the internal transcribed spacer (ITS), the 28S large subunit of ribosomal RNA (LSU), the second largest subunit of RNA polymerase II (RPB2), the ribosomal mitochondrial small subunit (mtSSU), and the translation elongation factor 1-α (TEF1-α) gene sequences, we here describe and illustrate two new species of Russula and one new species of Lactarius from southern China. These three new species are: R. junzifengensis (R. subsect. Virescentinae), R. zonatus (R. subsect. Crassotunicatae), and L. jianyangensis (L. subsect. Zonarii).

Assessing the structure and diversity of fungal community in plant soil under different climatic and vegetation conditions.

Introduction: Understanding microbial communities in diverse ecosystems is crucial for unraveling the intricate relationships among microorganisms, their environment, and ecosystem processes. In this study, we investigated differences in the fungal community structure and diversity in soils from two contrasting climatic and vegetation conditions: the Xinjiang western China plateau and the Fujian southeastern coastal province. Methods: A total of 36 soil samples collected from two climatic regions were subjected to high-throughput ITS gene sequencing for fungal community analysis. In conjunction soil physicochemical properties were assessed and compared. Analyses included an examination of the relationship of fungal community structure to environmental factors and functional profiling of the community structure was using the FUNGuild pipeline. Results: Our data revealed rich fungal diversity, with a total of 11 fungal phyla, 31 classes, 86 orders, 200 families, 388 genera, and 515 species identified in the soil samples. Distinct variations in the physicochemical properties of the soil and fungal community structure were seen in relation to climate and surface vegetation. Notably, despite a colder climate, the rhizosphere soil of Xinjiang exhibited higher fungal (α-)diversity compared to the rhizosphere soil of Fujian. ß-diversity analyses indicated that soil heterogeneity and differences in fungal community structure were primarily influenced by spatial distance limitations and vegetation type. Furthermore, we identified dominant fungal phyla with significant roles in energy cycling and organic matter degradation, including members of the Sordariomycetes, Leotiomycetes, Archaeosporomycetes, and Agaricomycetes. Functional analyses of soil fungal communities highlighted distinct microbial ecological functions in Xinjiang and Fujian soils. Xinjiang soil was characterized by a focus on wood and plant saprotrophy, and endophytes, whereas in Fujian soil the fungal community was mainly associated with ectomycorrhizal interactions, fungal parasitism, and wood saprotrophy. Discussion: Our findings suggest fungal communities in different climatic conditions adapt along distinct patterns with, plants to cope with environmental stress and contribute significantly to energy metabolism and material cycling within soil-plant systems. This study provides valuable insights into the ecological diversity of fungal communities driven by geological and environmental factors.

Highly strong and tough silk by feeding silkworms with rare earth ion-modified diets.

Nature-derived silk fibers possess excellent biocompatibility, sustainability, and mechanical properties, yet producing strong and tough silk fibers in a facile and large-scale manner remains a significant challenge. Herein, we report a simple method for preparing strong and tough silk fibers by feeding silkworms rare earth ion-modified diets. The resulting silk fibers exhibit significantly increased tensile strength and toughness, with average values of 0.85 ± 0.07 GPa and 156 ± 13 MJ m-3, respectively, and maximum values of 0.97 ± 0.04 GPa and 188 ± 19 MJ m-3, approaching those of spider dragline silk. Our findings suggest that the incorporation of rare earth ions (La3+ or Eu3+) into the silk fibers contributes to this enhancement. Structure analysis reveals a reduction in content and an improvement in orientation of ß-sheet nanocrystals in silk fibers. X-ray photoelectron spectroscopy analysis confirms the chemical interaction between rare earth ions with ß-sheet nanocrystals. The structural evolution and chemical interactions lead to the simultaneous enhancement in both strength and toughness. This work presents a simple, scalable, and effective strategy for producing ultra-strong and tough silk fibers with potential applications in areas requiring super structural materials, such as personal protection and aerospace.

Morphological and phylogenetic analyzes reveal two new species of Melanconiella from Fujian Province, China.

Introduction: Species of Melanconiella include a diverse array of plant pathogens as well as endophytic fungi. Members of this genus have been frequently collected from the family Betulaceae (birches) in Europe and North America. Little, however, if known concerning the distribution of Melanconiella and/or their potential as pathogens of other plant hosts. Methods: Fungi were noted and isolated from diseased leaves of Loropetalum chinense (Chinese fringe flower) and Camellia sinensis (tea) in Fujian Province, China. Genomic DNA was extracted from fungal isolates and the nucleotide sequences of four loci were determined and sued to construct phylogenetic trees. Morphological characteristics of fungal structures were determined via microscopic analyses. Results: Four strains and two new species of Melanconiella were isolated from infected leaves of L. chinense and C. sinensis in Fujian Province, China. Based on morphology and a multi-gene phylogeny of the internal transcribed spacer regions with the intervening 5.8S nrRNA gene (ITS), the 28S large subunit of nuclear ribosomal RNA (LSU), the second largest subunit of RNA polymerase II (RPB2), and the translation elongation factor 1-α gene (TEF1-α), Melanconiellaloropetali sp. nov. and Melanconiellacamelliae sp. nov. were identified and described herein. Detailed descriptions, illustrations, and a key to the known species of Melanconiella are provided. Discussion: These data identify new species of Melanconiella, expanding the potential range and distribution of these dark septate fungi. The developed keys provide a reference source for further characterization of these fungi.

Anti-PD-1/Her2 Bispecific Antibody IBI315 Enhances the Treatment Effect of Her2-Positive Gastric Cancer through Gasdermin B-Cleavage Induced Pyroptosis.

The majority of patients with human epidermal growth factor receptor 2 (Her2)-positive gastric cancer develop refractory to Her2-targeted therapy, where upregulation of immune checkpoints plays an essential role. Herein, a recombinant fully human IgG1 bispecific antibody IBI315 targeting both PD-1 and Her2 is developed  and its antitumor efficacy as well as the underlying mechanism is investigated. IBI315 crosslinks the physical interaction between Her2-positive tumor cells and PD-1-positive T cells, resulting in significantly enhanced antitumor effects compared to each parent antibody or their combination, both in vitro and in vivo mouse tumor models reconstituted with human immune cells using patient-derived xenografts and organoids. Moreover, IBI315 treatment also induces the recruitment and activation of immune cells in tumors. Mechanistically, IBI315 triggers gasdermin B (GSDMB)-mediated pyroptosis in tumor cells, leading to the activation and recruiments of T cells. The activated T cells secret IFNγ, enhancing GSDMB expression and establishing a positive feedback loop of T cell activation and tumor cell killing. Notably, GSDMB is found to be elevated in Her2-positive gastric cancer cells, providing a rationale for IBI315's efficacy. IBI315 is supported here as a promising bispecific antibody-based immunotherapy approach for Her2-positive gastric cancer in preclinical studies, broadening the therapeutic landscape of this patient population.

Monitoring blood pressure and cardiac function without positioning via a deep learning-assisted strain sensor array.

Continuous and reliable monitoring of blood pressure and cardiac function is of great importance for diagnosing and preventing cardiovascular diseases. However, existing cardiovascular monitoring approaches are bulky and costly, limiting their wide applications for early diagnosis. Here, we developed an intelligent blood pressure and cardiac function monitoring system based on a conformal and flexible strain sensor array and deep learning neural networks. The sensor has a variety of advantages, including high sensitivity, high linearity, fast response and recovery, and high isotropy. Experiments and simulation synergistically verified that the sensor array can acquire high-precise and feature-rich pulse waves from the wrist without precise positioning. By combining high-quality pulse waves with a well-trained deep learning model, we can monitor blood pressure and cardiac function parameters. As a proof of concept, we further constructed an intelligent wearable system for real-time and long-term monitoring of blood pressure and cardiac function, which may contribute to personalized health management, precise and early diagnosis, and remote treatment.

Inter-Shell Sliding in Individual Few-Walled Carbon Nanotubes for Flexible Electronics.

Few-walled carbon nanotube (FWCNT) is composed of a few coaxial shells of CNTs with different diameters. The shells in one tube can slide relatively to each other under external forces, potentially leading to regulated electrical properties, which are never explored due to experimental difficulties. In this work, the electromechanical response induced by inter-shell sliding of individual CNTs is studied and revealed the linear electrical current variation for the first time. Based on centimeter-long FWCNTs grown through chemical vapor deposition, controllable and reversible inter-shell sliding is realized while simultaneously recording the electrical current. Reversible and linear current variation with inter-shell sliding is observed, which is consistent with the proposed inter-shell tunneling model. Further, a silk fibroin-assisted transfer technique is developed for long CNTs and realized the fabrication of FWCNT-based flexible devices. Tensile stress can be applied on the FWCNTs@silk film encapsulated in elastic silicone to induce inter-shell sliding and thus controls electrical current, which is demonstrated to serve as a new human-machine interface with high reliability. Besides, it is foreseen that the electromechanical behaviors induced by inter-layer sliding in 1D nanotubes may also be extended to 2D layered materials, shedding new light on the fabrication of novel electronics.

Efficacy and safety of modified tetracycline dosing in a quadruple therapy for Helicobacter pylori: A retrospective single center study.

BACKGROUND: Although highly effective as a component of Helicobacter pylori (H. pylori) treatment regimen, tetracycline is associated with a high incidence of medication-related adverse events. Modified dosing of tetracycline as part of quadruple therapy may improve safety while providing comparable eradication rates. AIM: To evaluate the efficacy and safety of modified dosing of tetracycline in patients receiving tetracycline and furazolidone-containing quadruple therapy in patients with H. pylori infection. METHODS: Consecutive patients (10/2020-12/2021) who received tetracycline and furazolidone quadruple therapy for H. pylori infection at Sir Run Run Shaw Hospital were identified. All patients received tetracycline, furazolidone, proton pump inhibitor, and bismuth for 14 d as primary or rescue therapy. Modified tetracycline dose group received tetracycline 500 mg twice daily while standard group received 750 mg twice daily or 500 mg three times daily. RESULTS: Three hundred and ninety-four patients [mean age = 46.3 ± 13.9, male = 137 (34.8%), and 309 (78.4%) primary therapy] completed tetracycline and furazolidone quadruple therapy for H. pylori infection including those who received modified tetracycline dose in 157 and standard doses in 118 (750 mg twice daily) and 119 (500 mg three times daily). Eradication rates in the modified tetracycline dose group were 92.40% and in the standard groups, eradication rates were 93.20% for 750 mg twice daily group and 92.43% for 500 mg three times daily group, respectively, without statistical difference (P = 0.959). The incidence of adverse events was lower in the modified tetracycline dose (15.3% vs 32.3% and 29.4%; P = 0.002) compared to the standard dose group. CONCLUSION: In a real-world experience, modified tetracycline dosing as part of tetracycline and furazolidone quadruple therapy for 14 d demonstrated high efficacy, comparable to standard tetracycline dose regimens, with a favorable safety profile.

Apostasia Mitochondrial Genome Analysis and Monocot Mitochondria Phylogenomics.

Apostasia shenzhenica belongs to the subfamily Apostasioideae and is a primitive group located at the base of the Orchidaceae phylogenetic tree. However, the A. shenzhenica mitochondrial genome (mitogenome) is still unexplored, and the phylogenetic relationships between monocots mitogenomes remain unexplored. In this study, we discussed the genetic diversity of A. shenzhenica and the phylogenetic relationships within its monocotyledon mitogenome. We sequenced and assembled the complete mitogenome of A. shenzhenica, resulting in a circular mitochondrial draft of 672,872 bp, with an average read coverage of 122× and a GC content of 44.4%. A. shenzhenica mitogenome contained 36 protein-coding genes, 16 tRNAs, two rRNAs, and two copies of nad4L. Repeat sequence analysis revealed a large number of medium and small repeats, accounting for 1.28% of the mitogenome sequence. Selection pressure analysis indicated high mitogenome conservation in related species. RNA editing identified 416 sites in the protein-coding region. Furthermore, we found 44 chloroplast genomic DNA fragments that were transferred from the chloroplast to the mitogenome of A. shenzhenica, with five plastid-derived genes remaining intact in the mitogenome. Finally, the phylogenetic analysis of the mitogenomes from A. shenzhenica and 28 other monocots showed that the evolution and classification of most monocots were well determined. These findings enrich the genetic resources of orchids and provide valuable information on the taxonomic classification and molecular evolution of monocots.

Isolation of a highly virulent Metarhizium strain targeting the tea pest, Ectropis obliqua.

Introduction: Tea is one of the most widely consumed beverages around the world. Larvae of the moth, Ectropis obliqua Prout (Geometridae, Lepidoptera), are one of the most destructive insect pests of tea in China. E. obliqua is a polyphagus insect that is of increasing concern due to the development of populations resistant to certain chemical insecticides. Microbial biological control agents offer an environmentally friendly and effective means for insect control that can be compatible with "green" and organic farming practices. Methods: To identify novel E. obliqua biological control agents, soil and inset cadaver samples were collected from tea growing regions in the Fujian province, China. Isolates were analyzed morphologically and via molecular characterization to identity them at the species level. Laboratory and greenhouse insect bioassays were used to determine the effectiveness of the isolates for E. obliqua control. Results: Eleven isolates corresponding to ten different species of Metarhizium were identified according to morphological and molecular analyses from soil and/or insect cadavers found on tea plants and/or in the surrounding soil sampled from eight different regions within the Fujian province, China. Four species of Metarhizium including M. clavatum, M. indigoticum, M. pemphigi, and M. phasmatodeae were documented for the first time in China, and the other species were identified as M. anisopliae, M. brunneum, M. lepidiotae, M. majus, M. pinghaense, and M. robertsii. Insect bioassays of the eleven isolates of Metarhizium revealed significant variation in the efficacy of each isolate to infect and kill E. obliqua. Metarhizium pingshaense (MaFZ-13) showed the highest virulence reaching a host target mortality rate of 93% in laboratory bioassays. The median lethal concentration (LC50) and median lethal time (LT50) values of M. pingshaense MaFZ-13 were 9.6 × 104 conidia/mL and 4.8 days, respectively. Greenhouse experiments and a time-dose-mortality (TDM) models were used to further evaluate and confirm the fungal pathogenic potential of M. pingshaense MaFZ-13 against E. obliqua larvae. Discussion: Isolation of indigenous microbial biological control agents targeting specific pests is an effective approach for collecting resources that can be exploited for pest control with lowered obstacles to approval and commercialization. Our data show the presence of four different previously unreported Metarhizium species in China. Bioassays of the eleven different Metarhizium strains isolated revealed that each could infect and kill E. obliqua to different degrees with the newly isolated M. pingshaense MaFZ-13 strain representing a particularly highly virulent isolate potentially applicable for the control of E. obliqua larvae.

Genome-Wide Identification Analysis of the R2R3-MYB Transcription Factor Family in Cymbidium sinense for Insights into Drought Stress Responses.

Cymbidium sinense represents a distinctive Orchidaceae plant that is more tolerant than other terrestrial orchids. Studies have shown that many members of the MYB transcription factor (TF) family, especially the R2R3-MYB subfamily, are responsive to drought stress. This study identified 103 CsMYBs; phylogenetic analysis classified these genes into 22 subgroups with Arabidopsis thaliana. Structural analysis showed that most CsMYB genes contained the same motifs, three exons and two introns, and showed a helix-turn-helix 3D structure in each R repeat. However, the members of subgroup 22 contained only one exon and no intron. Collinear analysis revealed that C. sinense had more orthologous R2R3-MYB genes with wheat than A. thaliana and rice. Ka/Ks ratios indicated that most CsMYB genes were under purifying negative selection pressure. Cis-acting elements analysis revealed that drought-related elements were mainly focused on subgroups 4, 8, 18, 20, 21, and 22, and Mol015419 (S20) contained the most. The transcriptome analysis results showed that expression patterns of most CsMYB genes were upregulated in leaves in response to slight drought stress and downregulated in roots. Among them, members in S8 and S20 significantly responded to drought stress in C. sinense. In addition, S14 and S17 also participated in these responses, and nine genes were selected for the real-time reverse transcription quantitative PCR (RT-qPCR) experiment. The results were roughly consistent with the transcriptome. Our results, thus, provide an important contribution to understanding the role of CsMYBs in stress-related metabolic processes.

Disease Burden of Total and Early-Onset Colorectal Cancer in China from 1990 to 2019 and Predictions of Cancer Incidence and Mortality.

Background: Understanding the temporal trends in the epidemiology of colorectal cancer (CRC) and early-onset CRC (EOCRC) in China is essential for policymakers to develop appropriate strategies to reduce the CRC burden. Methods: The prevalence, incidence, mortality, years of life lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life years (DALYs) of CRC were obtained from the Global Burden of Disease (GBD) Study 2019. The incidence and mortality of CRC over the next 25 years were predicted. Results: From 1990 to 2019, the prevalence, incidence, and mortality of total CRC and EOCRC significantly increased in males, with milder trends in females. In 2019, the number of people living with CRC (or EOCRC) in China was approximately 3.4 (0.59) million, which was over seven (five) times higher than that in 1990. The DALYs, YLDs, and YLLs moderately increased from 1990 to 2019 in both sexes. The age-standardized mortality rate (ASMR) for females has shown a stable trend in total CRC, and a downward trend in EOCRC since 2000. While the ASMR for males showed increasing trends in total CRC and EOCRC. In 2019, the highest incidence, prevalence, YLDs, YLLs, and DALYs were all observed in the 65 to 69 age group, while the highest mortality was in the 70 to 74. By 2044, the incidence and deaths of CRC are expected to reach 1310 thousand and 484 thousand, respectively. For EOCRC, the incidence will peak at about 101 thousand around 2034, and the mortality will continuously decrease to a nadir at about 18 thousand around 2044. Conclusion: Although the age-standardized incidence and mortality of total CRC and EOCRC in China will reach a plateau, the number of incident cases and deaths of CRC have been increasing in the last three decades and will continue to increase in the next 25 years.

Carbon-Based Flexible Devices for Comprehensive Health Monitoring.

Traditional public health systems suffer from incomprehensive, delayed, and inefficient medical services. Convenient and comprehensive health monitoring has been highly sought after recently. Flexible and wearable devices are attracting wide attention due to their potential applications in wearable human health monitoring and care systems. Using carbon materials with overall superiorities can facilitate the development of wearable and flexible devices with various functions and excellent performance, which can comprehensively and real-time monitor human health status and prevent diseases. Herein, the latest advances in the rational design and controlled fabrication of carbon materials for applications in health-related flexible and wearable electronics are reviewed. The fabrication strategies, working mechanism, performance, and applications in health monitoring of carbon-based flexible devices, including electromechanical sensors, temperature/humidity sensors, chemical sensors, and flexible conductive wires/electrodes, are reviewed. Furthermore, integrating multiple carbon-based devices into multifunctional wearable systems is discussed. Finally, the existing challenges and future opportunities in this field are also proposed.

Genome-wide identification of YABBY genes in three Cymbidium species and expression patterns in C. ensifolium (Orchidaceae).

Members of the YABBY gene family play significant roles in lamina development in cotyledons, floral organs, and other lateral organs. The Orchidaceae family is one of the largest angiosperm groups. Some YABBYs have been reported in Orchidaceae. However, the function of YABBY genes in Cymbidium is currently unknown. In this study, 24 YABBY genes were identified in Cymbidium ensifolium, C. goeringii, and C. sinense. We analyzed the conserved domains and motifs, the phylogenetic relationships, chromosome distribution, collinear correlation, and cis-elements of these three species. We also analyzed expression patterns of C. ensifolium and C. goeringii. Phylogenetic relationships analysis indicated that 24 YABBY genes were clustered in four groups, INO, CRC/DL, YAB2, and YAB3/FIL. For most YABBY genes, the zinc finger domain was located near the N-terminus and the helix-loop-helix domain (YABBY domain) near the C-terminus. Chromosomal location analysis results suggested that only C. goeringii YABBY has tandem repeat genes. Almost all the YABBY genes displayed corresponding one-to-one relationships in the syntenic relationships analysis. Cis-elements analysis indicated that most elements were clustered in light-responsive elements, followed by MeJA-responsive elements. Expression patterns showed that YAB2 genes have high expression in floral organs. RT-qPCR analysis showed high expression of CeYAB3 in lip, petal, and in the gynostemium. CeCRC and CeYAB2.2 were highly expressed in gynostemium. These findings provide valuable information of YABBY genes in Cymbidium species and the function in Orchidaceae.

Multiple Bismuth Quadruple Therapy Containing Tetracyclines Combined with Other Antibiotics and Helicobacter pylori Eradication Therapy.

Helicobacter pylori (HP) infection is closely associated with the development of chronic gastritis, peptic ulcer, and gastric cancer. However, the resistance rate of H. pylori strains to antibiotics such as clarithromycin, metronidazole, and levofloxacin has increased significantly, resulting in a significant decrease in the eradication efficacy of commonly used regimens. Tetracycline has received the attention of domestic and foreign scholars because of its low resistance. The purpose of this review is to provide an update on the tetracycline-containing bismuth quadruple eradication therapy for H. pylori infection and review the efficacy and safety of the regimens, hoping to provide guidance for clinical practice.

Humidity-sensitive chemoelectric flexible sensors based on metal-air redox reaction for health management.

Numerous studies have shown flexible electronics play important roles in health management. The way of power supply is always an essential factor of devices and self-powered ones are very attractive because of the fabrication easiness, usage comfort and aesthetics of the system. In this work, based on the metal-air redox reaction, which is usually used in designing metal-air batteries, we design a self-powered chemoelectric humidity sensor where a silk fibroin (SF) and LiBr gel matrix containing parallel aligned graphene oxide (GO) flakes serve as the electrolyte. The abundant hydrophilic groups in GO/SF and the hygroscopicity of LiBr lead to tight dependence of the output current on the humidity, enabling the sensor high sensitivity (0.09 µA/s/1%), fast response (1.05 s) and quick recovery (0.80 s). As proofs of concept, we design an all-in-one respiratory monitoring-diagnosing-treatment system and a non-contact human-machine interface, demonstrating the applications of the chemoelectric humidity sensor in health management.

IBI379, a novel B cell maturation antigen/CD3 bispecific T-cell engager, displays high antitumor efficacy in preclinical models of multiple myeloma.

Multiple myeloma (MM) is a hematological malignancy that results from the malignant proliferation of plasma cells in the bone marrow. B cell maturation antigen (BCMA) is highly selectively expressed in malignant plasma cells and is a novel therapeutic target for MM. Here, we developed a bispecific T cell engager, IBI379, that targets BCMA and CD3, and investigated its antitumor efficacy against MM. IBI379 showed strong binding affinity with both BCMA and CD3, which triggered T cell activation, proliferation, and cytokine release. An in vitro study demonstrated that IBI379 induced the lysis of MM cells expressing differing levels of BCMA on the cell surface. Administration of IBI379 in H929 or Daudi-BCMA cell xenograft mouse models significantly inhibited tumor growth without inducing body weight loss. The mechanism of action study revealed the accumulation of CD4+CD8+ T cells and granzyme B-positive T cells in tumors that were treated with IBI379. Moreover, administration of low dose of IBI379 in cynomolgus monkeys was well-tolerated and induced the depletion of BCMA+ B cells and a mild transient increase of cytokines. Collectively, these results demonstrate that IBI379 is a highly potent therapeutic strategy for depleting BCMA-positive B cells and is a promising approach for the treatment of MM.

Genome-Wide Identification and Expression Analysis of Terpene Synthase Genes in Cymbidium faberi.

Terpene synthases (TPSs) are essential for forming terpenes, which play numerous functional roles in attracting pollinators, defending plants, and moderating the interaction between plants. TPSs have been reported in some orchids, but genome-wide identification of terpenes in Cymbidium faberi is still lacking. In this study, 32 putative TPS genes were classified in C. faberi and divided into three subfamilies (TPS-a, TPS-b, and TPS-e/f). Motif and gene structure analysis revealed that most CfTPS genes had the conserved aspartate-rich DDxxD motif. TPS genes in the TPS-a and TPS-b subfamilies had variations in the RRX8W motif. Most cis-elements of CfTPS genes were found in the phytohormone responsiveness category, and MYC contained most of the numbers associated with MeJA responsiveness. The Ka/Ks ratios of 12/13 CfTPS gene pairs were less than one, indicated that most CfTPS genes have undergone negative selection. The tissue-specific expression patterns showed that 28 genes were expressed in at least one tissue in C. faberi, and TPS genes were most highly expressed in flowers, followed by leaves and pseudobulbs. In addition, four CfTPS genes were selected for the real-time reverse transcription quantitative PCR (RT-qPCR) experiment. The results revealed that CfTPS12, CfTPS18, CfTPS23, and CfTPS28 were mainly expressed in the full flowering stage. CfTPS18 could convert GPP to ß-myrcene, geraniol, and α-pinene in vitro. These findings of CfTPS genes of C. faberi may provide valuable information for further studies on TPSs in orchids.