MSCs-engineered biomimetic PMAA nanomedicines for multiple bioimaging-guided and photothermal-enhanced radiotherapy of NSCLC.

BACKGROUND: The recently developed biomimetic strategy is one of the mostly effective strategies for improving the theranostic efficacy of diverse nanomedicines, because nanoparticles coated with cell membranes can disguise as "self", evade the surveillance of the immune system, and accumulate to the tumor sites actively. RESULTS: Herein, we utilized mesenchymal stem cell memabranes (MSCs) to coat polymethacrylic acid (PMAA) nanoparticles loaded with Fe(III) and cypate-an derivative of indocyanine green to fabricate Cyp-PMAA-Fe@MSCs, which featured high stability, desirable tumor-accumulation and intriguing photothermal conversion efficiency both in vitro and in vivo for the treatment of lung cancer. After intravenous administration of Cyp-PMAA-Fe@MSCs and Cyp-PMAA-Fe@RBCs (RBCs, red blood cell membranes) separately into tumor-bearing mice, the fluorescence signal in the MSCs group was 21% stronger than that in the RBCs group at the tumor sites in an in vivo fluorescence imaging system. Correspondingly, the T1-weighted magnetic resonance imaging (MRI) signal at the tumor site decreased 30% after intravenous injection of Cyp-PMAA-Fe@MSCs. Importantly, the constructed Cyp-PMAA-Fe@MSCs exhibited strong photothermal hyperthermia effect both in vitro and in vivo when exposed to 808 nm laser irradiation, thus it could be used for photothermal therapy. Furthermore, tumors on mice treated with phototermal therapy and radiotherapy shrank 32% more than those treated with only radiotherapy. CONCLUSIONS: These results proved that Cyp-PMAA-Fe@MSCs could realize fluorescence/MRI bimodal imaging, while be used in phototermal-therapy-enhanced radiotherapy, providing desirable nanoplatforms for tumor diagnosis and precise treatment of non-small cell lung cancer.

Au-polythionine nanocomposites: a novel mediator for bisphenol A dual-signal assay based on imprinted electrochemical sensor.

In this work, a novel electrochemical sensor was developed by the modification of poly(p-aminobenzene sulfonic acid) (pABSA), Au-polythionine (Au-pTH) nanowires, and molecularly imprinted polymer (MIP) on glassy carbon electrode surface for bisphenol A (BPA) detection. The results of characterizations including scanning electron microscope, transmission electron microscopy, Fourier transform infrared spectra, and X-ray diffraction showed the successful synthesis of helical structural Au-pTH nanowires, which acted as an electro-active probe for BPA detection. Cyclic voltammetry results illustrated that the modified pABSA, Au-pTH, and MIP endowed the sensor with good electrocatalytic activity, the second current signal, and recognition ability, respectively. Since the imprinted cavities provided electron transfer channels for thionine (TH) redox, the peak current of TH can be found in a blank electrolyte. The added BPA molecules can be rebound in imprinted cavities, which are oxidized and then display its current. The rebound BPA molecules in turn blocked the electron transfer channels for TH redox, resulting in the decrease of TH current. A double signal defined, as the sum of the changes of TH current (∆iTH|) and BPA current (|∆iBPA|) (|∆iTH|+|∆iBPA|), was employed as the detected signal for BPA sensitive detection, which was linearly proportional to the logarithm of concentration of BPA ranging from 8.0 × 10-8 to 1.0 × 10-4 mol/L with a limit of detection of 3.8 × 10-8 mol/L (S/N = 3) in a weakly acidic solution. Moreover, the natural recognition ability of MIP enabled the sensor to selectively detect BPA from its analogues. The proposed dual-signal strategy-based sensor provided a feasible tool for rapid, sensitive, and selective determination of BPA. Graphical abstract.

Diagnostic predictability of serum miR-4793-3p and miR-1180-3p expression in community-acquired pneumonia.

Background: Early identification of community-acquired pneumonia (CAP) is crucial to prevent severe progression. Methods: The authors enrolled 150 hospitalized CAP patients and collected clinicopathologic features and blood indicators. Plasma miRNA profiling was conducted using microarray detection, and selected miRNAs were tested with reverse transcription quantitative PCR. Predictive models were built using least shrinkage and selection operator regression. Results: Least shrinkage and selection operator regression identified two miRNAs (miR-4793-3p and miR-1180-3p) that distinguished mild from severe CAP patients (area under the curve = 0.948). The miRNA model outperformed D-dimer, platelet and procalcitonin (max area under the curve = 0.729). Conclusion: Increased levels of miR-4793-3p and miR-1180-3p may indicate severe pneumonia development. Plasma miRNA profiling enables early prediction of severe CAP, aiding therapeutic decisions.

Dataset of core and differentially abundant bacteria in various compartments of farm-cultivated and home-planted chilli plants (Capsicum frutescens).

Chillies are members of the genus Capsicum L. (family Solanaceae). They are native to Central and South America and consist of approximately 35 species [1,2]. Among these, five species (C. annuum L., C. baccatum L., C. chinense Jacq., C. frutescens L., and C. pubescens Ruiz & Pav.) have been domesticated and are mainly cultivated for consumption as vegetables and spices. Of the domesticated chillies, C. annuum is commercially cultivated worldwide, while C. frutescens and C. chinense are mainly cultivated in American, Asian, and African countries [3]. We compared the diversity of microbiota in various compartments of farm-cultivated (FC) and home-planted (HP) chilli plants (Capsicum frutescens). Targeted 16S rRNA gene (V5-V6 region) was sequenced using the Illumina NovaSeq 6000 platform. Proteobacteria, Actinobacteriota, Acidobacteriota, Gemmatimonadota, Bacteroidota, and Firmicutes were present in all compartments of both the FC and HP plants. Proteobacteria (or Pseudomonadota) was the predominant phylum in all the compartments of both HP and FC plants, while Actinobacteriota (or Actinomycetota) was the second most abundant phylum. Most plant compartments (leaves, fruits and roots) exhibited a higher relative abundance of Proteobacteria compared to the soil samples. With few exceptions, the soil compartments (bulk and rhizospheric soils) displayed a higher relative abundance of the phyla Myxococcota, Acidobacteriota, Gemmatimonadota, Bacteroidota, Nitrospirota, Verrucomicrobiota, and Firmicutes than the plant compartments. Diversity indices revealed that the bacterial community in chili plants clustered based on both compartment and cultivation area.

Myosin heavy chain isoform expression and meat quality characteristics of different muscles in yak (Bos grunniens).

Myosin heavy chain (MHC) isoforms and meat quality characteristics of different muscles were investigated to explore their potential relationships in yaks. Results showed that semitendinosus (ST), longissimus thoracis (LT), and infraspinatus (IS) have a greater ratio of MHC IIb (47.84%), MHC IIa (73.27%), and MHC I (24.26%), respectively, than the other two muscles. Compared with LT or ST, IS exhibited more intense color, greater water-holding capacity, and initial tenderness with higher intermuscular fat (IMF) and collagen (of lower cross-linking level), presenting overall better quality. Variations in MHC isoforms accounted for the muscle-specific meat quality. Specifically, MHC I was positively associated with redness, myoglobin, IMF, collagen, pH, and thermal stability and negatively associated with myofibril fragmentation index, fiber thickness, collagen cross-linking, and drip loss. These results provide insights into the relationships between MHC isoforms and meat quality in yaks and the MHC I isoform has an extensive influence on meat quality.

Different endodontic treatments induced root development of two nonvital immature teeth in the same patient: A case report.

BACKGROUND: Pulp revascularization is a novel way to treat immature teeth with periapical disease, and the technique has become increasingly well established in recent years. By puncturing the periapical tissue, bleeding is induced, and a blood clot is formed in the root canal. The blood clot acts as a natural bioscaffold onto which mesenchymal stem cells from periapical tissue can be seeded and restore pulp vascularity, thus promoting root development as well as apical closure. Although the effect of pulp revascularization is ideal, there are certain requirements for the apical condition of the teeth. The apical barrier technique and apexification are still indispensable for teeth that cannot achieve ideal blood clot formation. In addition, a meta-analysis of several clinical studies concluded that pulp revascularization has no significant advantages over other treatments. CASE SUMMARY: A 10-year-old girl complained of pain in the right upper and lower posterior teeth for 2 d. Clinical and radiological examinations revealed that both the right maxillary and mandibular second premolars were immature with periapical radiolucency. The right maxillary second premolar was treated by pulp revascularization, while the right mandibular second premolar was treated by conventional apical barrier surgery after revascularization failed. The purpose of this report is to compare the different root maturation processes induced by the pulp revascularization and apical barrier techniques in the same patient in homonymous teeth from different jaws. Twelve months of follow-up showed that the apical foramen of both teeth presented a clear tendency to close; however, the tooth treated with pulp revascularization showed a significant increase in root length as well as root canal wall thickness. CONCLUSION: For the treatment of nonvital immature teeth, pulp revascularization showed a superior therapeutic effect in comparison with the apical barrier technique.

The role of pyroptosis in inflammatory diseases.

Programmed cell death has crucial roles in the physiological maturation of an organism, the maintenance of metabolism, and disease progression. Pyroptosis, a form of programmed cell death which has recently received much attention, is closely related to inflammation and occurs via canonical, non-canonical, caspase-3-dependent, and unclassified pathways. The pore-forming gasdermin proteins mediate pyroptosis by promoting cell lysis, contributing to the outflow of large amounts of inflammatory cytokines and cellular contents. Although the inflammatory response is critical for the body's defense against pathogens, uncontrolled inflammation can cause tissue damage and is a vital factor in the occurrence and progression of various diseases. In this review, we briefly summarize the major signaling pathways of pyroptosis and discuss current research on the pathological function of pyroptosis in autoinflammatory diseases and sterile inflammatory diseases.

Secondary structure construction and molecular identification of rRNA 18S V4 region E23-5-E23-6 of parasitic lice of Hominidae.

The parasitic lice of Hominidae are a class of blood-sucking insects, having a large fragment expansion region in ribosome 18S V4 region. In this study, the value of the E23-5-E23-6 stem-loop structure in the insertion region for molecular identification of lice were explored through motif analysis and secondary structure construction. Five pubic lice samples from China were morphologically identified, and primers for the rRNA 18S V4 region were designed for molecular identification. The V4 sequence of the parasitic lice of Hominidae was retrieved from GenBank for sequence analysis. The five samples were identified as pubic lice based on V4 region, which were of the same specie but geographically different from Australian strains in Genbank, with the identity of 99.06-99.46%. Compared with the human lice, both the chimpanzee lice and pubic lice had large indel fragments in the V4 region. Comparison results showed that Muscle and MAFFT had better alignment and phylogeny results than Clustal. The large expansion region, comprising E23-5 and E23-6, was located between E23-4 and E23-7. The V4 secondary structure showed that the stem-loop structures of the lice parasitizing on pubic area, human, and chimpanzee were different in the E23-5 and E23-6, which could effectively distinguish the three parasitic lice and divide the human lice into five genotypes. This is suitable not only for the identification of three lice species in higher taxonomic ranks but also for genotype identification of human lice in lower taxonomic ranks. The difference between the stem-loop structure is more intuitive than that between the primary sequences.

Effect of slaughter age and postmortem aging time on tenderness and water-holding capacity of yak (Bos grunniens) longissimus thoracis muscle.

The present study investigated the effect of slaughter age (2.43 ± 0.20, 4.15 ± 0.19, 6.62 ± 0.18, 10.59 ± 0.74 years) and postmortem aging time (1, 24, and 72 h) on the tenderness and water-holding capacity (WHC) of yak longissimus thoracis muscles to determine the most suitable age for slaughter to ensure product consistency. Under conventional postmortem aging conditions (4 °C), muscles of each age group exhibited the effect of cold shortening. Once the cold shortening occurred, the age effect on thickening muscle fiber and developing cross-links of collagen, considered to intensify the meat toughness, became less important. Owing to greater carcass weight and intramuscular fat, muscles of the older carcass (over 6-year-old) were less influenced by the cold shortening effect during the chilling process and showed lessened sarcomere contraction, delayed formation of drip loss channels, and increased level of myofibril fragmentation index (MFI) and myofiber structural disintegration, resulting in greater tenderness and WHC, especially 6-7 years group. Aging of 72 h structurally disintegrated the collagen cross-linking and integrity of muscle fibers and elevated the MFI, improving the meat tenderness. Therefore, the suitable slaughter age for yak is 6-7 years old and after 72 h aging, improved quality of yak meat can be obtained.

Classification and identification of mosquitoes in China based on rDNA 28S D5 region.

Accurate classification and identification of mosquitoes are essential for the prevention and control of mosquito-borne diseases. In this study, adult mosquitoes were collected from 15 cities across 14 provinces in China. They were identified morphologically with the dominant species determined. Furthermore, representative samples were identified at the molecular level based on rDNA 28S D5. In total, 880 adult mosquitoes were collected belonging to Culex (266), Aedes (473), Armigeres (13), and Anopheles (5). Aedes albopictus and "C. pipiens subgroup" were the dominant species. A total of 140 sequences of 28S D5 region (68 for "C. pipiens subgroup", 51 for Ae. albopictus, 18 for Ar. subalbatus, and three for An. sinensis) ranging from 148 to 161 bp were obtained, with 100 % success of amplification and sequencing. Molecular identification were consistent with morphological classification. Sequence analysis showed that "C. pipiens subgroup" was identified into three clades: the traditional C. pipiens subgroup (Clade I), the newly discovered C. cf. perexiguus (Clade II), and C. new sp. (Clade III). Clade I contained the most abundant haplotypes (16) widely distributed without geographical differences. Clade II included six haplotypes that were aggregately distributed south of the Yangtze River. Only three sequences in Clade III showed two haplotypes with no geographical differences. Further morphological comparisons demonstrated differences in body color, beaks, and abdomens among the three clades. In conclusion, the rDNA 28S D5 region could effectively distinguish Culex, Aedes, Armigeres, and Anopheles species at the lower category level, demonstrating its potential as a mini-DNA barcode for mosquito identification.

Cloning, sequencing, expression, and purification of aspartic proteases isolated from two human Demodex species.

Aspartic proteases (ASPs) are important hydrolases for parasitic invasion of host tissues or cells. This was the first study on Demodex ASP. First, the complete coding sequence (CDS) was amplified, cloned and sequenced. Then, the protein physical and chemical properties was analysed. Finally, the recombinant plasmid, expression and purification system was established. Results showed that the lengths of CDS of Demodex folliculorum and D. brevis were 1161 and 1173 bp, respectively. The molecular weight of the protein was approximately 40 KDa. It contained an aspartic acid residue, a substrate-binding site and signal peptide, yet lacked a transmembrane domain and was located in the membrane or extracellular matrix. The phylogenetic and conserved motif analyses showed that D. folliculorum and D. brevis clustered separately and then formed a single branch, which finally clustered with other Acariformes species. The prokaryotic expression systems for recombinant ASP with His-tag (rASP-His) and GST-tag (rASP-GST) were constructed. The inclusion bodies of rASP-His were renaturated by gradient urea and purified using NI beads, while those of rASP-GST were renaturated by sarkosyl and Triton X-100 and purified using GST beads. Conclusively, the prokaryotic expression and purification system of Demodex rASP was successfully established for further pathogenic mechanism research.

[Bioinformatic research of the family of PEX11, peroxisome proliferous factor in fungus].

The family members of PEX11 are key factors involved in regulation of peroxisome proliferation. Sixty-six PEX11p candidates of PEX11 gene family from 26 representative fungal species were obtained and analyzed by bioinformatic strategies. In most filamentous fungi, 2 or 3 potential PEX11ps were found, in contrast with 1 or 2 in yeast species. Compared with other fungal species, the Ascomycetes tend to have more PEX11ps, and even 5 in several individuals. The data of phylogenetic analysis and protein structure indicated that all of the PEX11ps were divided into 3 groups: I, II, and III. The members of group I and group III existed in most species, while those in group II were found only in Pezizomycotina. By MEME analysis, 5-6 conserved motifs were found in each PEX11ps. Among them,motif 8 in C-terminal had the most conservation, indicating that this motif probably plays a key role in maintaining the proper function of PEX11p.

Oxygen-evolving photosynthetic cyanobacteria for 2D bismuthene radiosensitizer-enhanced cancer radiotherapy.

The local hypoxic tumor environment substantially hampers the therapeutic efficiency of radiotherapy, which typically requires the large X-ray doses for tumor treatment but induces the serious side effects. Herein, a biomimetic radiosensitized platform based on a natural in-situ oxygen-evolving photosynthetic cyanobacteria combined with two-dimensional (2D) bismuthene with high atomic-number (Z) components, is designed and engineered to effectively modulate the radiotherapy-resistant hypoxic tumor environment and achieve sufficient radiation energy deposition into tumor. Upon the exogenous sequential irradiation of 660 nm laser and X-ray beam, continuous photosynthetic oxygen evolution by the cyanobacteria and considerable generation of reactive oxygen species by the 2D bismuthene radiosensitizer substantially augmented the therapeutic efficacy of radiotherapy and suppressed the in vivo tumor growth, as demonstrated on both LLC-lung tumor xenograft-bearing C57/B6 mice model and 4T1-breast tumor xenograft-bearing Balb/c mice model, further demonstrating the photosynthetic hypoxia-alleviation capability and radiosensitization performance of the engineered biomimetic radiosensitized platform. This work exemplifies a distinct paradigm on the construction of microorganism-enabled tumor-microenvironment modulation and nanoradiosensitizer-augmented radiotherapy for efficient tumor treatment.

A pulmonary lymphangioleiomyomatosis with multi-site angiomyolipoma: a case report.

Background: Lymphangioleiomyomatosis (LAM) is a rare low-grade malignant tumor featured with diffuse cystic changes due to the destructive proliferation of LAM cells, closely related to angiomyolipoma (AML). Here, we reported a rare case of pulmonary LAM coexisting with AMLs in multiple sites of the lung, liver, kidney, and retroperitoneum. We aimed to contribute to the body of knowledge regarding the diagnosis, identification and treatment of such cases. Case Description: A 48-year-old female with no symptoms underwent a chest computed tomography (CT) scan that showed diffuse thin-walled cysts and multiple solid nodules in the lungs. She received a right nephrectomy due to right kidney AML 30 years previously. The pathological manifestations of the right lower lung mass removed by thoracoscopic surgery was a multifocal AML with mutations in the tuberous sclerosis complex gene. Abdominal magnetic resonance imaging (MRI) reveals a vast area of fat signal shadow behind the peritoneum and multiple scattered fatty signal nodules in the liver parenchyma. No other treatment was given due to personal factors of the patient, and there was no significant change at the 1-year follow-up. Conclusions: LAM and AML are two different but substantively related rare neoplastic diseases. When typical LAM imaging features are found on chest CT or in pathological specimens collected from patients diagnosed with AML, multisystem screening should be performed for the early detection and diagnosis of LAM.

Age-specific effect on endogenous oxidative and antioxidative characteristics of longissimus thoracis muscle of yak during early postmortem period.

Effects of age on postmortem redox states were investigated in yak muscles. Extended postmortem time reduced the muscle antioxidant capacity and induced oxidation in lipids, myoglobin, and proteins. Compared with older yaks, muscles of younger ones could delay this oxidation process due to lower initial myoglobin content of 30.7%, lipid peroxidation of 42.4%, H2O2 of 41.2%, and intramuscular fat of 65.6% (of 3.66 times higher PUFAs). They also possessed greater antioxidase content/activity, such as phospholipase A2 content of 30.7% and glutathione reductase activity of 50.6%. Muscles exhibited age-specific overall antioxidative characteristics during 72 h postmortem and gradually formed overall oxidative ones after 72 h postmortem with an initial similarity between 2- and 4-year (or 6- and 12-year) on canonical discriminant analyses. The formation of age-specific overall oxidative characteristics can be attributable to the antioxidative specificity of age on canonical correlation analyses. Age-specific redox characteristics required differentiated preference in meat processing and preservation.

Muscle fiber composition affects the postmortem redox characteristics of yak beef.

Yak infraspinatus (IS), longissimus thoracis (LT), and semitendinosus (ST) muscles were used to explore relationships between myofiber types and postmortem redox characteristics. IS mainly consisted of myofiber type Ⅰ (49.2%), LT has a vast majority of type IIa (72.7%), while ST possessed a similar percentage of type IIa (44.7%) and IIb (51.5%). Compared with LT and ST, IS exhibited higher initial H2O2, myoglobin (T-Mb), and metmyoglobin (MetMb) contents that provoked severe protein oxidation despite higher endogenous antioxidative capacity (e.g., glutathione antioxidative system). Three muscles showed specificities in myofiber type composition and redox characteristics, which were strongly correlated. Specifically, type Ⅰ myofiber positively correlated with H2O2, T-Mb, and multiple antioxidase activity/content while negatively correlated with lipid peroxidation, MetMb, and lactic dehydrogenase activity; also, they tended to employ more SFAs in more intermuscular fat assembly. Overall, muscle-specific myofiber type/redox attributes required differentiated processing to prevent meat oxidation and produce standardized products.

Stressors of Nursing Interns and Their Influencing Factors: A Cross-Sectional Study.

Objective: It is still unknown whether the stress level and stressors in Chinese nursing interns are influenced by teacher-related factors. This research was carried out for better understanding of the stress in nursing interns and distribution of stressors during their clinical practice and targeted measures to unwind the stress of nursing interns. Methods: A questionnaire survey, titled Questionnaire on Stressors of Nursing Interns during Clinical Practice, was conducted on nursing interns at a 3A Grade Hospital in Shandong Province. Characteristics of the nursing interns and stressors of nursing interns were collected. A multiple-linear regression model was used to explore the influencing factors of nursing interns' scores. Results: A total of 132 nursing interns were investigated in this study, and the overall stress scores were calculated. The stressors during the internship include the nature and content of the job, role orientation, workload, conflict between study and work, practice preparation, and interpersonal relationships. Gender, education level, instructor encouragement, and parents engaged in the medical industry were adjusted in the multiple-linear regression model as covariates. All of these factors had significant impacts on the scores of stressors (P < 0.05), with the partial regression coefficient values of 13.38, -10.52, -5.02, 3.4, -9.89, -14.77, and -15.83 for factors like female, undergraduates, graduate students, never obtained encouragement from teachers, obtained encouragement from teachers occasionally, obtained encouragement from teachers frequently, and parents engaged in the medical industry, respectively. Conclusion: The stressors of nursing interns are mostly work-wise, and teachers' encouragement is an important protective factor for nursing interns to reduce stress. Therefore, clinical instructors should take targeted measures in teaching methods and work arrangements according to the needs of interns.

Sensitive and selective detection of glycoprotein based on dual-signal and dual-recognition electrochemical sensing platform.

Glycoproteins play extraordinary roles in biology and clinic. The specifically sensitive detection of glycoproteins by electrochemical methods is still a challenging task due to their poor electro-activity and sensitive nature to environment. In this work, ovalbumin (OVA), a model glycoprotein, was sensitively detected by a molecularly imprinted polymer (MIP) based electrochemical sensor, which was prepared by electropolymerizing 3-thiophene boric acid in the presence of OVA. Due to boronate affinity, the rebound OVA interacted with ferrocene boric acid (Fc-BA) to construct a sandwich structural sensing platform. Dual-recognition elements, imprinted effect and the boronate affinity, enabled the sensor to recognize OVA from other proteins. The rebinding of OVA caused the current changes of thionine and Fc-BA, which were combined as a dual-signal for OVA sensitive detection with a low limit of detection of 0.82 pg/mL (S/N = 3). The good performances of sensor indicated its potential applications in clinical diagnosis and other related fields.

Patterns of Failure in Patients With Advanced Non-Small Cell Lung Cancer Treated With Immune Checkpoint Inhibitors.

OBJECTIVE: The advent of immune checkpoint inhibitors (ICIs) has rapidly transformed the treatment paradigm of non-small cell lung cancer (NSCLC). Despite the durability of response to ICIs, the vast majority of patients will later develop progression. However, the failure patterns of ICI treatment are unknown. Here, our study explored the failure patterns in advanced NSCLC patients treated with ICIs. METHODS: A cohort of 156 IIIB or IV NSCLC patients treated with first-/second-line ICIs were retrospectively analyzed. Patients who experienced clinical benefit and then developed progression were identified. The disease progression patterns were divided into three categories: progression in new sites, progression in existing sites, and combined progression. The number of progression sites was also recorded. RESULTS: Before the cutoff date, 91 (77.1%) patients had experienced disease progression; 34% of patients had progressed in the last 9 months of the first year. Fifty-three (58.2%) patients had developed progression at existing lesions, and 56 (61.5%) patients had shown ≤2 progression sites (oligo-progression). In patients with oligo-progression, the median time of disease progression was 8.23 months and the counterpart (systemic progression) was 5.97 months. The oligo-progression patients showed prolonged median overall survival (27.23 months) compared with patients with systemic progression (18.87 months). CONCLUSIONS: Failure patterns of ICI therapy were predominantly "existing" sites, and the most common lesions of progression were the lung and lymph nodes. Most patients experienced oligo-progression which occurred later than systemic progression and showed prolonged overall survival. The control of the local lesions might be beneficial to improve ICI treatment efficacy.

MAT Loci Play Crucial Roles in Sexual Development but Are Dispensable for Asexual Reproduction and Pathogenicity in Rice Blast Fungus Magnaporthe oryzae.

Magnaporthe oryzae, a fungal pathogen that causes rice blast, which is the most destructive disease of rice worldwide, has the potential to perform both asexual and sexual reproduction. MAT loci, consisting of MAT genes, were deemed to determine the mating types of M. oryzae strains. However, investigation was rarely performed on the development and molecular mechanisms of the sexual reproduction of the fungus. In the present work, we analyzed the roles of two MAT loci and five individual MAT genes in the sex determination, sexual development and pathogenicity of M. oryzae. Both of the MAT1-1 and MAT1-2 loci are required for sex determination and the development of sexual structures. MAT1-1-1, MAT1-1-3 and MAT1-2-1 genes are crucial for the formation of perithecium. MAT1-1-2 impacts the generation of asci and ascospores, while MAT1-2-2 is dispensable for sexual development. A GFP fusion experiment indicated that the protein of MAT1-1-3 is distributed in the nucleus. However, all of the MAT loci or MAT genes are dispensable for vegetative growth, asexual reproduction, pathogenicity and pathogenicity-related developments of the fungus, suggesting that sexual reproduction is regulated relatively independently in the development of the fungus. The data and methods of this work may be helpful to further understand the life cycle and the variation of the fungus.