Complete remission of advanced pancreatic cancer induced by claudin18.2-targeted CAR-T cell therapy: a case report

Pancreatic cancer (PC) is one of the most malignant tumors in digestive system due to its highly invasive and metastatic properties. At present, conventional treatment strategies for PC show the limited clinical efficacy. Therefore, novel effective therapeutic strategies are urgently needed. Here, we report a case of complete remission of advanced PC induced by claudin18.2-targeted CAR-T cell therapy. The patient was a 72-year-old man who was diagnosed with pancreatic ductal adenocarcinoma 2 years ago, and he experienced tumor recurrence and multiple metastases after pancreaticoduodenectomy and multi-line chemotherapies, including liver, peritoneum, and cervical lymph node metastases. Then, the patient was referred to our department for further treatment of metastatic PC, and he was enrolled in a clinical trial of claudin18.2-targeted CAR-T cell therapy. After lymphodepleting chemotherapy, the patient received claudin18.2-targeted CAR-T cell infusion at a dose of 1.2 × 106 cells/kg on November 21, 2022. During CAR-T cell therapy, the patient experienced grade 2 cytokine release syndrome (CRS) and gastric mucosa injury, which were controlled by tocilizumab and conventional symptomatic and supportive treatment. The patient achieved a complete response (CR) 1 month after claudin18.2-targeted CAR-T cell therapy, and remained in clinical remission for 8 months. Unfortunately, the patient experienced claudin18.2-negative relapse in July, 2023. Despite antigen-negative relapse after claudin18.2-targeted CAR-T cell infusion, the patient achieved sustained remission for 8 months, which indicates that claudin18.2-targeted CAR-T cell therapy is an extremely effective therapeutic strategy for the treatment of advanced PC

Case report: Gene mutations and clinical characteristics of four patients with osteopetrosis

Osteopetrosis is characterized by increased bone density caused by decreased osteoclasts or dysfunction of their differentiation and absorption properties, usually caused by biallelic variants of the TCIRG1(OMIM:604592)and CLCN7(OMIM:602727) genes. Herein, the clinical, biochemical, and radiological manifestations of osteopetrosis in four Chinese children are described. Whole-exome sequencing identified compound heterozygous variants of the CLCN7 and TCIRG1 genes in these patients. In Patient 1, two novel variants were identified in CLCN7:c.880T > G(p.F294V) and c.686C > G(p.S229X). Patient 2 harbored previously reported a single gene variant c.643G > A(p.G215R) in CLCN7. Patient 3 had a novel variant c.569A > G(p.N190S) and a novel frameshift variant c.1113dupG(p.N372fs) in CLCN7. Patient 4 had a frameshift variant c.43delA(p.K15fs) and variant c.C1360T in TCIRG1, resulting in the formation of a premature termination codon (p.R454X), both of which were reported previously. Our results expand the spectrum of identified genetic variation in osteopetrosis and provide a deeper understanding of the relations between genotype and clinical characteristics of this disorder

Numerical Studies on the Performance of the PCM Mesh-Finned Heat Sink Base on Thermal-Flow Multiphysics Coupling Simulation

Operating temperature is an important parameter of thyristors to ensure the stable operation of power electronic devices. Thermal management technology is of great significance for improving the reliability of thyristors. In this study, the performance of a phase change material (PCM) mesh-finned heat sink is investigated for the thermal management of thyristors. A multi-physical coupling model of the PCM mesh-finned heat sink is established to analyze the effects of different power losses, air velocities, heights of fins, and thickness of PCM on the thermal performance of the PCM heat sink. The influence of thermal and flow fields on PCM is considered in this model. Furthermore, the heat sink design is optimized to improve the thermal performance based on the calculation results of thermal network parameters. The results show that the power losses, the air velocity, the height of fins, and the thickness of PCM significantly affect the protection ability of the PCM heat sink. After optimizing the heat sink, the PCM heat sink provides 80 s protection time and 100 s recovery time. The PCM mesh-finned heat sink demonstrated good potential for the thermal management of thyristors

Waste apple wood: A safe and economical alternative substrate for the cultivation of Pleurotus ostreatus and Lentinula edodes

The use of waste apple-wood as a source of sawdust to cultivate the mushrooms Pleurotus ostreatus and Lentinula edodes is a common practice, but it is imperative to ensure that the wood does not contain unsafe amounts of heavy-metals or pesticide residues. In this study, we sampled and investigated the pollution of heavy metals and pesticide residues in apple-wood from Yantai, Shandong, China and cultivated P. ostreatus and L. edodes using apple-wood as substrate. Heavy metals, pesticide residues, mineral elements, and biological efficiency were measured. Heavy metals were more commonly detected in the 73 apple-wood samples, but serious pollution was only an isolated phenomenon. No Pb was detected in P. ostreatus and L. edodes. The contents of Hg, As, Cd, and Cr were at safe levels. The contents of Ni were equivalent to those of wild mushrooms. Most notably, chlorpyrifos was detected in all the apple-wood tested. However, chlorpyrifos was only detected in L. edodes cultivated with apple sawdust. No other pesticide residues were detected in the other mushroom samples. The biological efficiency of P. ostreatus cultivated by apple sawdust was 89%, which was 80% of the control. The biological efficiency of L. edodes cultivated with apple sawdust was 81%, which did not differ significantly from the control. Apple-wood can replace wild oak as the material for L. edodes cultivation, but producers should ensure that the raw materials are safe. The main materials chosen to cultivate P. ostreatus should balance the two factors of raw material price and biological efficiency

Multiplex Detection of Pleurotus ostreatus Mycoviruses

Mycoviruses are viruses that specifically infect and replicate in fungi. Several mycoviruses have been previously reported in Pleurotus ostreatus, including the oyster mushroom spherical virus (OMSV), oyster mushroom isometric virus (OMIV), Pleurotus ostreatus spherical virus (POSV), and Pleurotus ostreatus virus 1 (PoV1). This study was designed to develop a multiplex RT-PCR for simultaneous detection and differentiation of the four P. ostreatus mycoviruses. Four pairs of primers were designed from conserved regions based on the reported sequences and the multiplex RT-PCR products were 672 bp for OMSV, 540 bp for OMIV, 310 bp for POSV, and 200 bp for PoV1. The optimal annealing temperature of the multiplex RT-PCR was 62 °C and the detection limits of the plasmids were 100 fg for OMSV and OMIV and 1 pg for POSV and PoV1. This technique was successfully applied for the detection of OMSV, OMIV, and POSV from different P. ostreatus strains and the plasmid containing the PoV1 sequence. This methodology can serve as a powerful diagnostic tool for the survey of the incidence and epidemiology of the four P. ostreatus mycoviruses, further contributing to the prevention and treatment of mycoviral diseases in P. ostreatus

Power Allocation for Cooperative Non-Orthogonal Multiple Access Systems

Cooperative non-orthogonal multiple access (NOMA) has attracted more and more attentions recently, in which NOMA-strong users play as relays to help the data transmission of NOMA-weak users. Different from existing works, we study the problem of power allocation for cooperative NOMA systems with half-duplex relaying mode. From a fairness standpoint, our proposed scheme aims at maximizing the minimum achievable user rate in a paired user group. More specifically, we divide the cooperative NOMA systems into two categories, i.e., fixed relaying scheme and adaptive relaying scheme. Fixed relaying scheme means the transmit power at the relay node, namely PR, is a given fixed constant while adaptive relaying scheme implies that PR$ can adapt to channel conditions according to our strategy. It is shown that the formulated power allo

Supramolecular assemblies of cucurbit[n]urils and 4-aminopyridine controlled by cucurbit[n]uril size (n = 5, 6, 7 and 8)

The binding interactions between 4-aminopyridine (4-AP) and a series of cucurbit[n]urils (Q[5], Q[6], TMeQ[6], Q[7], Q[8]) have been studied using 1H NMR spectroscopy, UV–vis absorption spectroscopy, isothermal titration calorimetry (ITC) and X-ray crystallography. The data indicates that the Q[5]@4-AP complex exhibits exo binding, which is not observed in the other four host-guest complexes. Furthermore, X-ray crystallography clearly reveals how the Q[n]s bind with 4-AP to form complexes, for example Q[5] forms an outer-surface complex, whilst Q[6], TMeQ[6] and Q[7] formed a 1:1 host and guest type complex, and Q[8] formed a stable 1:2 ternary complex due to its large cavity, which can accommodate two 4-AP molecules

PersonalityScanner: Exploring the Validity of Personality Assessment Based on Multimodal Signals in Virtual Reality

Human cognition significantly influences expressed behavior and is intrinsically tied to authentic personality traits. Personality assessment plays a pivotal role in various fields, including psychology, education, social media, etc. However, traditional self-report questionnaires can only provide data based on what individuals are willing and able to disclose, thereby lacking objective. Moreover, automated measurements and peer assessments demand significant human effort and resources. In this paper, given the advantages of the Virtual Reality (VR) technique, we develop a VR simulator --- PersonalityScanner, to stimulate cognitive processes and simulate daily behaviors based on an immersive and interactive simulation environment, in which participants carry out a battery of engaging tasks that formulate a natural story of first-day at work. Through this simulator, we collect a synchronous multi-modal dataset with ten modalities, including first/third-person video, audio, text, eye tracking, facial microexpression, pose, depth data, log, and inertial measurement unit. By systematically examining the contributions of different modalities on revealing personality, we demonstrate the superior performance and effectiveness of PersonalityScanner

Gender differences in quality of life among patients with myasthenia gravis in China

Background: Myasthenia gravis (MG), a chronic neuromuscular disorder, can adversely affect patients\u27 health-related quality of life (HRQoL), especially in women. The study aimed to evaluate the difference in HRQoL of women and men MG patients and explore the factors that mediate the relationship between gender and HRQoL. Methods: A cross-sectional study was conducted among 1815 patients with MG in China. The revised 15-item MG quality of life scale (MG-QOL15r) was used to access patients\u27 HRQoL in overall, physical, social and emotional domains. Socio-demographic information, diagnosis and treatment history, comorbidities, social support, active lifestyle and the MG activities of daily living scale (MG-ADL) were recorded and compared between women and men using the Student\u27s t-test and Pearson\u27s Chi-square test. Multivariable regression analyses were conducted to identify independent contributors to HRQoL, especially those affecting different gender. Results: On average, female patients with MG reported a lower MG-QOL15r score than the males (44.49 ± 29.10 vs 49.32 ± 29.18). The association between gender and patients\u27 HRQoL interacted with the number of comorbidities across the overall, physical and social domains of patients. As the number of comorbidities increased, the scores of HRQoL decreased and it was faster among females than the males (p \u3c 0.05). Moreover, unemployment, exacerbation of the disease, and active lifestyle contributed to the patients\u27 HRQoL across all domains. Unemployment (β = - 4.99 [95%CI, - 7.80 to - 2.18], p \u3c 0.001) and exacerbations (β = - 8.49 [95%CI, - 11.43 to - 5.54], p \u3c 0.001) were correlated with poorer HRQoL; while an active lifestyle had a positive impact on HRQoL (β = 0.28 [95%CI, 0.16 to 0.40], p \u3c 0.001). Conclusions: The results indicate that the HRQoL of women MG patients was lower than that of men. The relationship between gender and HRQoL is modulated by the number of comorbidities. Thus, to improve the HRQoL of women MG patients, symptomatic treatments might not be enough, their comorbid conditions should be considered as well. Additionally, employment status, MG exacerbations, and an active lifestyle have been found as determining factors of the patients\u27 HRQoL, which suggests future interventions should cope with these factors to improve their quality of life