Natural killer cells as a double-edged sword in cancer immunotherapy: A comprehensive review from cytokine therapy to adoptive cell immunotherapy.

Natural killer (NK) cells are immune cells which are able to kill tumor and virus-infected cells and play an important role in both innate immunity and acquired immunity. Tumor immunotherapy is an emerging model of tumor treatment in the clinic. It is a re-emerging type of anticancer immunotherapy with the purpose of killing tumor cells by modulating the body's immune function and enhancing the antitumor immunity in tumor microenvironment. At present, many immune cells including lymphokine-activated killer cells, NK cells, cytokine-induced killer cells, and dendritic cells are involved in tumor immunotherapy studies. NK cells, which lyse tumor cells without prior stimulation, has become a research hotspot in cancer immunotherapy for clinical application. In this article, we discussed the surface receptors of NK cells and the anticancer function of NK cells. We also reviewed the biological characteristics and the current research status of NK cells, their clinical application in cancer immunotherapy and its future perspectives.

Geographical and temporal changes of foliar fungal endophytes associated with the invasive plant Ageratina adenophora.

Endophytes may gradually accumulate in the new geographic range of a non-native plant, just as pathogens do. To test this hypothesis, the dynamics of colonization and diversity of foliar fungal endophytes of non-native Ageratina adenophora were investigated. Previous reports showed that the time since the initial introduction (1930s) of A. adenophora into China varied among populations. Endophytes were sampled in three provinces of Southwest China in 21 sites that varied from 20 to 70 years since the introduction of A. adenophora from its native Central America. Endophyte isolation frequencies varied from 1.87% to 60.23% overall in a total of 4,032 leaf fragments. Based on ITS sequence variations, 463 fungal endophytes were distinguished as 112 operational taxonomic units (OTUs) belonging to the Sordariomycetes (77 OTUs, 373 isolates), Dothideomycetes (18 OTUs, 38 isolates), and Agaricomycetes (17 OTUs, 52 strains) classes. Colletotrichum (28.51%), Nemania (14.90%), Phomopsis (13.17%), and Xylaria (4.97%) were the most abundant genera. Both endophyte diversity and overall isolation frequency increased with time since introduction. The genetic differentiation of the fungus Colletotrichum gloeosporioides indicated that the dispersal of endophytes was likely affected by a combination of geographic factors and the invasion history of the host A. adenophora.

Parasitic leiomyoma of the greater omentum: a case report and literature review.

Parasitic leiomyomas (PL), also known as free leiomyomas, which occur outside the uterus and rarely happen in clinical practice. They are usually reported in women of reproductive age who underwent hysterectomy or myomectomy and frequently present with symptoms such as abdominal pain and distention. In fact, it is hard to determine the nature of the mass according to the imaging examination and clinical manifestation. At present, the most common treatment involves an abdominal or laparoscopic surgery in order to remove the mass and perform the next step of treatment based on the histological diagnosis. In this case report, we describe a 35-year-old woman with a 12.4 × 9.3 × 9.8 cm3 PL with blood supply from the greater omentum. Considering the prolonged menstruation of the patient, she underwent the hysteroscopic and laparotomy exploration. The mass was confirmed as smooth leiomyoma with necrosis by the immunohistochemical examination. The patient had a good recovery and being discharged seven days after the surgery. The patient is still in the follow-up.

Firing feature-driven neural circuits with scalable memristive neurons for robotic obstacle avoidance.

Neural circuits with specific structures and diverse neuronal firing features are the foundation for supporting intelligent tasks in biology and are regarded as the driver for catalyzing next-generation artificial intelligence. Emulating neural circuits in hardware underpins engineering highly efficient neuromorphic chips, however, implementing a firing features-driven functional neural circuit is still an open question. In this work, inspired by avoidance neural circuits of crickets, we construct a spiking feature-driven sensorimotor control neural circuit consisting of three memristive Hodgkin-Huxley neurons. The ascending neurons exhibit mixed tonic spiking and bursting features, which are used for encoding sensing input. Additionally, we innovatively introduce a selective communication scheme in biology to decode mixed firing features using two descending neurons. We proceed to integrate such a neural circuit with a robot for avoidance control and achieve lower latency than conventional platforms. These results provide a foundation for implementing real brain-like systems driven by firing features with memristive neurons and put constructing high-order intelligent machines on the agenda.

Case report: Cheek acupuncture exhibits an immediate effect in relieving severe pain associated with nerve compression or damage of central nervous system and its potential mechanism of action.

Peripheral nerve compression or permanent damage of central nervous system (CNS) can trigger severe neuralgia to patients. Analgesic medicine or even surgery to remove nerve compression is commonly used for pain relief. But these treatments either are ineffective, have side-effect or can cause subsequent complications. Acupuncture, a technique that has been widely used in China and other Asian countries for thousands of years, is an alternative to relieve pain, although the mechanism of action is not fully understood. In this study, two patients who had symptoms of severe neuralgia associated with peripheral nerve compression or permanent damage/dysfunction of CNS and analgesic medicines are ineffective, underwent cheek acupuncture, a new technique established recent years by the author with the features of painless, standardization, simplicity, and precision. An immediate analgesic effect of the cheek acupuncture was observed without any side effects, and clinical remission was achieved after several sessions of treatments. It suggests that this new approach is an efficient alternative for pain relief induced by nerve impairment. The authors proposed a biological holographic model of triplet homunculi existing at the level of the local cheek, spinal cord, and cerebral cortex, to explain the immediate and accurate analgesic effect of the cheek acupuncture. These homunculi have the same structure, and synchronized sensations and actions that are mediated by afferent and efferent neurons, as the integrated human body. Therefore, the nociception and needling signals are sensed, transmitted, analyzed, and manipulated cooperatively and simultaneously among these homunculi with the subsequent pain relief in the body.

Prognostic effect of lncRNA BBOX1-AS1 in malignancies: a meta-analysis.

Background: With the increasing number of new cancer cases and mortality rates, cancer has become a serious global health problem, but there are no ideal cancer biomarkers for effective diagnosis. Currently, mounting evidence demonstrates that lncRNAs play a fundamental role in cancer progression. BBOX1 anti-sense RNA 1 (BBOX1-AS1) is a recently clarified lncRNA and has been identified as dysregulated in various carcinomas, and it contributes to poor survival in cancer patients. Methods: We thoroughly searched six databases for eligible articles published as of 27, April 2023. The association of BBOX1-AS1 expression levels with prognostic and clinicopathological parameters was assessed by odds ratios (OR) and hazard ratios with 95% CIs. Additionally, we further validated our results utilizing the GEPIA online database. Results: Eight studies comprising 602 patients were included in this analysis. High BBOX1-AS1 expression indicated poor overall survival (OS) (hazard ratios = 2.30, 95% Cl [1.99, 2.67], p < 0.00001) when compared with low BBOX1-AS1 expression. Furthermore, BBOX1-AS1 expression was positively correlated with lymph node metastasis (OR = 3.00, 95% CI [1.71-5.28], p = 0.0001) and advanced tumor stage (OR = 3.74, 95% CI [2.63-5.32], p < 0.00001) for cancer patients. Moreover, BBOX1-AS1 was remarkably upregulated in 12 malignancies, and the elevated BBOX1-AS1 expression predicted poorer OS and worse disease-free survival (DFS) confirmed through the GEPIA online gene analysis tool. Conclusion: The findings highlight that BBOX1-AS1 was significantly associated with detrimental overall survival, disease-free survival, lymph node metastasis and tumor stage; thus, it could act as a novel promising biomarker to predict the clinicopathological characteristics and prognosis for various cancers.

Granular cell tumor of the vulva: Case report and systematic review of the literature.

RATIONALE: Granular cell tumor (GCT) of the vulva is an exceptionally rare female genital tract tumor. The majority of these are benign and there are no standardized surgical techniques for the special site to reduce tension of the wound. PATIENT CONCERNS: A 47-years-old Chinese woman experienced a nodule on her right vulva with itch sometimes in late 2018. DIAGNOSES: Magnetic resonance imaging showed a high possibility of vulvar cancer. While Chest X-ray, abdominal sonography, and cystoscopy examination were unremarkable. INTERVENTIONS: The patient underwent local complete resection of vulvar tumor under general anesthesia on March 24, 2022. The resection scope was approximately 4 cm × 3 cm × 3 cm. Due to the large surgical incision, Z-plasty was performed to achieve the primary closure for decreasing wound tension and improving aesthetic reduction. OUTCOMES: The final pathological diagnosis was benign GCT of the vulva and surgical margins were uninvolved. At 8 months follow-up, no new lesions were detected. LESSONS: Surgery with negative resection margins is the mainstay for benign GCT of the vulva, while Z-plasty is appropriate for decreasing the tension of the wound and improving aesthetic reduction.

Meta analysis of the effect of phloroglucinol combined with progesterone in the treatment of threatened miscarriage before 20 weeks of gestation: A protocol for a systematic review.

BACKGROUND: Threatened miscarriage (TM) is an important factor endangering the health of pregnant women. It not only affects women's physical and mental health, but also destroys family happiness. To treat this disease, it is necessary to find a treatment with better clinical efficacy and fewer side effects. The purpose of this systematic study was to evaluate the efficacy and safety of phloroglucinol (PHL) combined with progesterone in the treatment of TM before 20 weeks of pregnancy. METHODS: Electronic databases (EMBASE, PubMed, Cochrane Central Register of Controlled Trials, Web of Science, Elsevier, China National Knowledge Infrastructure, Chongqing VIP, and WanFang Data) were searched from inception until September. 2022. Randomized controlled trials of PHL combined with progesterone in the treatment of TM before 20 weeks of gestation will be included, and all articles will be independently screened and collected by 2 reviewers. Revman 5.3.5 software will be used for meta-analysis. The specific process is described in the Cochrane Handbook for Systematic Reviews. RESULTS: The efficacy and safety of PHL combined with progesterone for the treatment of threatened abortion were comprehensively evaluated in terms of efficacy, efficiency, time of symptom relief, length of hospital stay, and incidence of adverse events. CONCLUSION: This study provides reliable evidence for the clinical application of PHL combined with progesterone for the treatment of TM.

A Heterogeneously Integrated Spiking Neuron Array for Multimode-Fused Perception and Object Classification.

Multimode-fused sensing in the somatosensory system helps people obtain comprehensive object properties and make accurate judgments. However, building such multisensory systems with conventional metal-oxide-semiconductor technology presents serious device integration and circuit complexity challenges. Here, a multimode-fused spiking neuron (MFSN) with a compact structure to achieve human-like multisensory perception is reported. The MFSN heterogeneously integrates a pressure sensor to process pressure and a NbOx -based memristor to sense temperature. Using this MFSN, multisensory analog information can be fused into one spike train, showing excellent data compression and conversion capabilities. Moreover, both pressure and temperature information are distinguished from fused spikes by decoupling the output frequencies and amplitudes, supporting multimodal tactile perception. Then, a 3 × 3 MFSN array is fabricated, and the fused frequency patterns are fed into a spiking neural network for enhanced tactile pattern recognition. Finally, a larger MFSN array is simulated for classifying objects with different shapes, temperatures, and weights, validating the feasibility of the MFSNs for practical applications. The proof-of-concept MFSNs enable the building of multimodal sensory systems and contribute to the development of highly intelligent robotics.

Compact artificial neuron based on anti-ferroelectric transistor.

Neuromorphic machines are intriguing for building energy-efficient intelligent systems, where spiking neurons are pivotal components. Recently, memristive neurons with promising bio-plausibility have been developed, but with limited reliability, bulky capacitors or additional reset circuits. Here, we propose an anti-ferroelectric field-effect transistor neuron based on the inherent polarization and depolarization of Hf0.2Zr0.8O2 anti-ferroelectric film to meet these challenges. The intrinsic accumulated polarization/spontaneous depolarization of Hf0.2Zr0.8O2 films implements the integration/leaky behavior of neurons, avoiding external capacitors and reset circuits. Moreover, the anti-ferroelectric neuron exhibits low energy consumption (37 fJ/spike), high endurance (>1012), high uniformity and high stability. We further construct a two-layer fully ferroelectric spiking neural networks that combines anti-ferroelectric neurons and ferroelectric synapses, achieving 96.8% recognition accuracy on the Modified National Institute of Standards and Technology dataset. This work opens the way to emulate neurons with anti-ferroelectric materials and provides a promising approach to building high-efficient neuromorphic hardware.

Phylogenetic Analysis of the Plant U2 snRNP Auxiliary Factor Large Subunit A Gene Family in Response to Developmental Cues and Environmental Stimuli.

In all organisms, splicing occurs through the formation of spliceosome complexes, and splicing auxiliary factors are essential during splicing. U2AF65 is a crucial splicing cofactor, and the two typical RNA-recognition motifs at its center recognize and bind the polypyrimidine sequence located between the intron branch site and the 3'-splice site. U2AF65A is a member of the U2AF65 gene family, with pivotal roles in diseases in mammals, specifically humans; however, few studies have investigated plant U2AF65A, and its specific functions are poorly understood. Therefore, in the present study, we systematically identified U2AF65A in plant species from algae to angiosperms. Based on 113 putative U2AF65A sequences from 33 plant species, phylogenetic analyses were performed, followed by basic bioinformatics, including the comparisons of gene structure, protein domains, promoter motifs, and gene expression levels. In addition, using rice as the model crop, we demonstrated that the OsU2AF65A protein is localized to the nucleus and cytoplasm, and it is involved in responses to various stresses, such as drought, high salinity, low temperature, and heavy metal exposure (e.g., cadmium). Using Arabidopsis thaliana and rice mutants, we demonstrated that U2AF65A is involved in the accumulation of plant biomass, growth of hypocotyl upon thermal stimulation, and reduction of tolerance of high temperature stress. These findings offer an overview of the U2AF65 gene family and its stress response functions, serving as the reference for further comprehensive functional studies of the essential specific splicing cofactor U2AF65A in the plant kingdom.

Bismuth Vanadium Oxide Can Promote Growth and Activity in Arabidopsis thaliana.

The excellent properties of nanomaterials have been confirmed in many fields, but their effects on plants are still unclear. In this study, different concentrations of bismuth vanadate (BV) were added to the growth medium to analyze the growth of seedlings, including taproots, lateral roots, leaf stomata, root activity, and superoxide anion O2 .- generation. Gene expression levels related to root growth were determined by quantitative PCR in Arabidopsis thaliana. The results showed that BV promoted the growth of taproots and the development of lateral roots, enhanced the length of the extension zone in roots, increased the number and size of leaf stomata and root activity, reduced the accumulation of ROS in seedlings, and changed the expression levels of genes related to polyamines or hormones. At the same time, we investigated the antibacterial activity of BV against a variety of common pathogens causing crop diseases. The results showed that BV could effectively inhibit the growth of Fusarium wilt of cotton and rice sheath blight. These results provide a new prospect for the development of nanomaterial-assisted plants, which is expected to become one of the ways to solve the problem of controlling and promoting the development of plants. At the same time, it also provides a reference for the study of the effect of BV on plants.

Role of GA3, GA4 and uniconazole-P in controlling gravitropism and tension wood formation in Fraxinus mandshurica Rupr. var. japonica Maxim. seedlings.

GA(3) and GA(4) (gibberellins) play an important role in controlling gravitropism and tension wood formation in woody angiosperms. In order to improve our understanding of the role of GA(3) and GA(4) on xylem cell formation and the G-layer, we studied the effect of GA(3) and GA(4) and uniconazole-P, which is an inhibitor of GA biosynthesis, on tension wood formation by gravity in Fraxinus mandshurica Rupr. var. japonica Maxim. seedlings. Forty seedlings were divided into two groups; one group was placed upright and the other tilted. Each group was further divided into four sub-groups subjected to the following treatments: 3.43 x 10(-9) micromol acetone as control, 5.78 x 10(-8) micromol gibberellic acid (GA(3)), 6.21 x 10(-8) micromol GA(4), and 6.86 x 10(-8) micromol uniconazole-P. During the experimental period, GAs-treated seedlings exhibited negative gravitropism, whereas application of uniconazole-P inhibited negative gravitropic stem bending. GA(3) and GA(4) promoted wood fibers that possessed a gelatinous layer on the upper side, whereas uniconazole-P inhibited wood formation but did not inhibit the differentiation of the gelatinous layer in wood fibers on the upper side. These results suggest that: (i) both the formation of gelatinous fibers and the quantity of xylem production are important for the negative gravitropism in horizontally-positioned seedlings; (ii) GA(3) and GA(4) affect wood production more than differentiation of the gelatinous layer in wood fibers; G-layer development may be regulated by other hormones via the indirect-role of GA(3) and GA(4) in horizontally-positioned F. mandshurica seedlings rather than the direct effect of GAs; and (iii) the mechanism for upward wood stem bending is different to the newly developed shoot bending in reaction to gravity in this species.

Baicalein induces cervical cancer apoptosis through the NF-κB signaling pathway.

To investigate the mechanism of baicalein in inducing human cervical cancer cell line C33A apoptosis. Baicalein (200 µM) was used to treat C33A cells. Cell proliferation was tested by the MTT assay. Cell apoptosis was detected by the TUNEL assay and caspase­3 activity measurement. Cell cycle was determined by flow cytometry and associated gene expression at mRNA and protein levels. Nuclear factor (NF)­κB activity was assessed by luciferase assay and western blotting. Baicalein suppressed cervical cancer cell C33A proliferation and induced cell apoptosis by activating caspase­3 activity. Baicalein blocked cell cycle in G0/G1 phase through regulating the expression of associated genes. Baicalein inhibited NF­κB activity by repressing nuclear translocation. Baicalein suppressed C33A proliferation and promoted cellular apoptosis by inhibiting NF­κB signaling pathway. In conclusion, the results indicate that baicalein can inhibit cervical cancer cell proliferation and promote cell apoptosis by affecting NF-κB activity.

Three-dimensional printing of shape memory hydrogels with internal structure for drug delivery.

Hydrogels with shape memory behavior and internal structure have wide applications in fields ranging from tissue engineering and medical instruments to drug delivery; however, creating the hydrogels has proven to be extremely challenging. This study presents a three-dimensional (3D) printing technology to fabricate the shape memory hydrogels with internal structure (SMHs) by combining sodium alginate (alginate) and pluronic F127 diacrylate macromer (F127DA). SMHs were constituted by a dual network structure. One is a stable network which is formed by F127DA photo-crosslinking; the other one is a reversible network which is formed by Ca2+ cross-linked alginate. SMHs recovery ratio was 98.15% in 10min after Ca2+ was removed in the Na2CO3 solution, and the elastic modulus remains essentially stable after the shape memory cycle. It showed that the drug releasing rate is more rapid compared with traditional drug-loaded hydrogels in in vitro experiments. The viability of 3T3 fibroblasts remained intact which revealed its excellent biocompatibility. Therefore, SMHs have a huge prospect for application in drug carriers and tissue engineering scaffold.

The restraining effect of baicalein and U0126 on human cervical cancer cell line HeLa.

To explore the restraining effect of baicalein and the mitogen-activation protein kinase kinase inhibitor, U0126, on human cervical cell line HeLa proliferation, apoptosis and migration. HeLa cells were treated by different concentrations of baicalein or U0126. A Cell Counting Kit (CCK)­8 assay was applied to examine cell viability. Flow cytometry was used to determine cell cycle and apoptosis. A wound healing assay was performed to detect cell migration. A terminal deoxynucleotidyl transferase dUTP nick end labeling assay was adopted to test cell apoptosis. Reverse transcription­quantitative polymerase chain reaction and western blot analysis was used to detect apoptosis gene and protein expression. CCK­8 assay demonstrated that baicalein and U0126 suppressed HeLa cell viability by dose dependence. TUNEL, Annexin V­fluorescein isothiocyanate/propidium iodide, and ratio of Bcl­2­associated X protein and B cell lymphoma 2 indicated that baicalein and U0126 induced HeLa cell apoptosis. Flow cytometry revealed that baicalein blocked the cell cycle of HeLa in G0/G1 phase. A wound healing assay demonstrated that baicalein significantly inhibited HeLa cell migration compared with control. Baicalein and U0126 markedly downregulated extracellular signal­regulated kinase 1/2, matrix metalloproteinase (MMP) 2 and MMP9 levels both in mRNA and protein. In the present study, the authors demonstrated that baicalein and U0126 may be used in cervical cancer treatment by inhibiting cell migration and inducing cell apoptosis.

[Baicalein promotes the apoptosis of HeLa cells by inhibiting ERK1/2 expression].

Objective To investigate the effects of baicalein and U0126 treatment on the apoptosis of human cervical carcinoma HeLa cells and the potential mechanism. Methods HeLa cells were subjected to (1, 2, 5, 10, 20, 50, 100, 200, 300) µmol/L baicalein or (1, 2, 5, 10, 20, 30) µmol/L U0126 treatment for 24 hours. The optimal concentrations of baicalein and U0126 for HeLa inhibition was determined by a cell counting Kit-8 assay. HeLa cells were then treated with these inhibitory concentrations for 24 hours separately or in combination. The cell cycle and the degree of apoptosis were analyzed by flow cytometry. The cell apoptosis index was evaluated by the TUNEL assay. The expressions of extracellular signal-regulated kinase 1/2 (ERK1/2), Bax, and Bcl-2 at the mRNA and protein levels were examined by real-time PCR and Western blotting, respectively. Results Optimal inhibitory concentrations of baicalein and U0126 for HeLa cells were 200 µmol/L and 10 µmol/L, respectively. Compared with the control group, baicalein treatment increased the growth rate of cells in the G0/G1 phase but decreased the S phase. Combination treatment of 200 µmol/L baicalein and 10 µmol/L U0126 for 24 hours further reduced the S phase growth rate. Treatment with 10 µmol/L U0126 or 200 µmol/L baicalein for 24 hours induced cell apoptosis, and the combination treatment induced more apoptosis. Treatment by baicalein alone or in combination with U0126 for 24 hours significantly decreased ERK1/2 and Bcl-2 mRNA expressions, and upregulated Bax mRNA expression. It also downregulated ERK1/2 phosphorylation and Bcl-2 protein expression, while increasing Bax protein expression. Conclusion Both baicalein and U012 appear to inhibit proliferation, induce apoptosis, and increase the growth rate in the G0/G1 phase but reduce the S phase of HeLa cells. This effect is enhanced when they are used synergistically.

[Internationalization and innovation of abdominal acupuncture].

Characteristics of abdominal acupuncture are analyzed through three aspects of inheriting and innovation, collaborated research as well as international visual field. It is pointed that abdominal acupuncture is based on clinical practice, focuses on enhancing the therapeutic effect and expending the clinical application. It also promots the thinking on how to recall the tradition and how to inherit tradition availably. The modern medical problems should be studied and innovation resolutions should be searched, which can help the internationalization and modernization of abdominal acupuncture.

[Enlightenment and thinking on deqi (arrival of needling sensation) by abdominal acupuncture].

Enlightened by clinical practice of new acupuncture techniques such as abdominal acupuncture, different recognitions on deqi (arrival of needling sensation), namely qi sensation under the tip of the needles and qi sensation at the affected region were analyzed in this article. The cause and effect relation of arrival of the qi sensation and effectiveness was unscrambled. Varying from the commonly accepted concept of qi sensation, a new concept of latent needling sensation which took the clinical effectiveness as the standard is proposed as a result to provide theoretical preparations for the clinical practice of painlessness acupuncture.