An expanded odorant-binding protein mediates host cue detection in the parasitic wasp Baryscapus dioryctriae basis of the chromosome-level genome assembly analysis.

BACKGROUND: Baryscapus dioryctriae (Chalcidodea: Eulophidae) is a parasitic wasp that parasitizes the pupae of many Pyralidae members and has been used as a biological control agent against Dioryctria pests of pinecones. RESULTS: This B. dioryctriae assembly has a genome size of 485.5 Mb with a contig N50 of 2.17 Mb, and scaffolds were assembled onto six chromosomes using Hi-C analysis, significantly increasing the scaffold N50 to 91.17 Mb, with more than 96.13% of the assembled bases located on chromosomes, and an analysis revealed that 94.73% of the BUSCO gene set. A total of 54.82% (279.27 Mb) of the assembly was composed of repetitive sequences and 24,778 protein-coding genes were identified. Comparative genomic analysis demonstrated that the chemosensory perception, genetic material synthesis, and immune response pathways were primarily enriched in the expanded genes. Moreover, the functional characteristics of an odorant-binding protein (BdioOBP45) with ovipositor-biased expression identified from the expanded olfactory gene families were investigated by the fluorescence competitive binding and RNAi assays, revealing that BdioOBP45 primarily binds to the D. abietella-induced volatile compounds, suggesting that this expanded OBP is likely involved in locating female wasp hosts and highlighting a direction for future research. CONCLUSIONS: Taken together, this work not only provides new genomic sequences for the Hymenoptera systematics, but also the high-quality chromosome-level genome of B. dioryctriae offers a valuable foundation for studying the molecular, evolutionary, and parasitic processes of parasitic wasps.

Advanced gallbladder cancer with high tumor mutation burden: a case report and literature review.

Background: Gallbladder cancer (GBC) is a common malignant tumor of the biliary system. It is characterised by insidious onset, rapid progression and poor prognosis. Symptoms often indicate advanced or late-stage disease, with a 5-year survival rate of only 5-15%. Case Description: We present a case study of a patient with GBC who had a tumor mutation burden (TMB) of 32.5/MB (≥10 muts/MB). The patient received mFOLFIRINOX as first-line chemotherapy, which demonstrated significant efficacy. After stabilizing the disease, a sequential chemotherapy regimen was chosen. This regimen combined the immune checkpoint inhibitor (ICI) toripalimab (JS001), a humanised IgG4 monoclonal antibody targeting programmed cell death protein 1 (PD-1), with S-1 therapy, an oral fluoropyrimidine derivative. However, this treatment did not provide any significant clinical benefit for the patient. Therefore, we hypothesise that combining immunotherapy with chemotherapy may be more effective as a first line treatment for high-TMB advanced GBC. This hypothesis needs to be validated in large-scale clinical studies. Conclusions: In summary, mFOLFIRINOX is a safe and effective first-line chemotherapy regimen for advanced GBC. The timing of combining immunotherapy with chemotherapy requires careful consideration. Further clinical trials involving immunotherapy in advanced GBC are necessary to identify biomarkers that can guide clinical decisions.

Reversible Cl/Cl- redox in a spinel Mn3O4 electrode.

A unique prospect of using halides as charge carriers is the possibility of the halides undergoing anodic redox behaviors when serving as charge carriers for the charge-neutrality compensation of electrodes. However, the anodic conversion of halides to neutral halogen species has often been irreversible at room temperature due to the emergence of diatomic halogen gaseous products. Here, we report that chloride ions can be reversibly converted to near-neutral atomic chlorine species in the Mn3O4 electrode at room temperature in a highly concentrated chloride-based aqueous electrolyte. Notably, the Zn2+ cations inserted in the first discharge and trapped in the Mn3O4 structure create an environment to stabilize the converted chlorine atoms within the structure. Characterization results suggest that the Cl/Cl- redox is responsible for the observed large capacity, as the oxidation state of Mn barely changes upon charging. Computation results corroborate that the converted chlorine species exist as polychloride monoanions, e.g., [Cl3]- and [Cl5]-, inside the Zn2+-trapped Mn3O4, and the presence of polychloride species is confirmed experimentally. Our results point to the halogen plating inside electrode lattices as a new charge-storage mechanism.

Transcriptome analysis and identification of genes related to environmental adaptation of Grylloprimevala jilina Zhou & Ren 2023.

Grylloprimevala jilina is a true cave insect living in the dark areas of caves. It has the characteristics of sparse skin pigmentation, degeneration of the compound eyes and monocular eyes, and obvious preference for high-humidity and low-temperature environments. Given the highly specialized, rare, and limited distribution, G. jilina is considered an endangered species and also a first-level national protected insect in China. Cave creatures often undergo dramatic morphological changes in their sensory systems to adapt to the cave environment. Most previous studies mainly focused on morphological adaptive changes in cave insects, and only a few studied the changes at the gene level. In this study, we performed transcriptome analysis of G. jilina and constructed phylogenetic trees of genes that are related to environmental adaptation, including chemosensory, visual-related, reproduction-related, temperature adaptation-related, and winged morph differentiation-related genes. Besides, the expression levels of environmental adaption-related genes in different tissues, including antennae, heads, thoraxes, abdomens, legs, and tails, were analyzed. The results showed the loss of chemosensory genes and vision-related genes, the conservation of reproduction-related genes and temperature adaptation-related genes, and the conservation of wing-related genes despite the loss of wings, and the results were consistent with other cave insects. The identification and expression study of genes possibly related to the environmental adaptability in G. jilina provided basic data for the protection of this endangered species and increased knowledge about insect evolution in general.

Case report: Composite mantle cell lymphoma and classical Hodgkin lymphoma.

Composite mantle cell lymphoma and classical Hodgkin lymphoma is very rare and the actual origin of it is still unclear. Here we reported a new case of composite mantle cell lymphoma and classical Hodgkin lymphoma and analyzed its molecular changes. Eight mutations were identified in its Hodgkin component through next-generation sequencing. In addition, we reviewed the published cases of composite mantle cell lymphoma and classical Hodgkin lymphoma and summarized the molecular changes of reported cases as well as the current case to explore the possible pathway of histogenesis.

Human epididymis protein 4 (HE4) is a novel immunohistochemical marker of neuroendocrine differentiation.

Human epididymis protein 4 (HE4) is originally described as an epididymis specific protein and now clinically used as a serum marker for ovarian carcinoma. However, the expression of HE4 in neuroendocrine neoplasms (NENs) has not been studied. By immunohistochemistry, the expressions of HE4 in 94 normal tissues and 484 NENs which included 242 well-differentiated NENs and 242 poorly differentiated NENs were studied. HE4 was positive in 90/94 (95.7%) of the neuroendocrine cells in normal tissues, 228/242 (94.2%) of well-differentiated NENs, and 206/242 (85.1%) of poorly differentiated NENs, and the expression of HE4 decreased progressively with loss of histological differentiation, with the positive rate of 96.2%, 92.7%, 92.3%, 85.4%, and 84.4% in NET-G1/carcinoid, NET-G2/atypical carcinoid, NET-G3, NEC-LC, and NEC-SC respectively. In NET-G1 and NET-G2, HE4 staining showed a peculiar polarized distribution, with an extraordinarily strong granular staining in subnuclear cytoplasm. A diffuse and uniform cytoplastic HE4 staining was observed in NET-G3 and poorly differentiated NENs. The positive rate of HE4 in primary tumors (91.1%, 387/425) was significantly higher than that of metastases (79.7%, 47/59) (p < 0.05). In a series of 70 pure non-NENs poorly differentiated carcinomas, the specificity rate of HE4 was 92.9% (65/70), which was in line with that of Syn. The negative rate of HE4 was 87.0% (40/46) in the non-neuroendocrine components of the MiNEN cases, which was lower than that of the pure non-neuroendocrine carcinomas (92.9%, 65/70) but without statistical significance (p > 0.05). HE4 may prove to be a useful immunohistochemical marker of neuroendocrine differentiation, although comparative studies and a more extensive analysis of other tissue types are necessary.

The study of clinicopathologic features of cervical squamous carcinoma with invasive micropapillary like pattern and phenotype.

Invasive micropapillary carcinoma has been reported in the adenocarcinoma of many organs including cervix, and many studies have proved it has more invasive biological behavior. This study, for the first time, reports cervical squamous carcinoma with invasive micropapillary like pattern and phenotype (IMLPP) and further investigates its clinicopathologic features. Cervical squamous carcinoma with IMLPP was selected by histological characteristics and immunohistochemical staining. All patients' clinical information and pathological parameters were collected. Based on histological characteristics and immunohistochemical staining results, 24 cases, out of 104 cases of cervical squamous carcinoma, were identified as having invasive micropapillary like pattern. The staining of all 24 cases with EMA and MUC-1 showed the feature of "reverse polarity like". Meanwhile, patient age at diagnosis (P=0.011), maximum invasion depth (P=0.001), maximum diameter (P=0.015), lymphvascular space invasion (P<0.001), pelvic lymph node metastasis (P<0.001), metastasis (P=0.020), death (P=0.025) and FIGO stages (P=0.001) were related to the existence of IMLPP, independently of the proportion of IMLPP to the whole tumor in size. Univariate and multivariate disease-free survival analyses (follow-up time >12 months) showed significant statistical difference between cervical squamous carcinoma with or without IMLPP (P=0.016, P=0.043). Results from our study suggested that IMLPP may be associated with aggressive biological behavior in cervical squamous carcinoma. Therefore, pathologists should pay attention to the existence of it, no matter its proportion with relation to the whole tumor, and bring it to the attention of clinicians.

Discovery of Lijianmin-Chengkun Complexes and Their Oncological Application in Osseous and Intraarticular Lesions Around the Knee.

Objective: This research aims to refresh the limited understanding about the canal and vascular structures within the epiphysis and metaphysis of the tibia and femur and their oncological significance. Methods: This study was started with characterization of a novel structure using radiographs and anatomic dissections, followed by a descriptive clinical study with 55 participants to investigate the effects of tumors on this novel discovery and a retrospective cohort study with 82 participants to investigate whether the structure would be a risk factor for tumor recurrence after the curettage of giant cell tumor of bone. Results: A new anatomical knee structure, the Lijianmin-Chengkun (LC) complex, was discovered in healthy adults, and its clinical implications were examined in this study. This new-found anatomical structure is composed of an epiphyseal and metaphyseal canal which surrounds a blood vessel, foramen, and foramen-covered synovium. All LC complexes showed similar radiographical, anatomical, and histological characteristics and were located within specific tibial and femoral intercondylar regions. These LC complexes seem to facilitate tumor residue and extension and may be a risk factor for tumor recurrence after curettage of femoral and tibial giant cell tumors (P = 0.031). Conclusion: The LC complexes are related to local tumor recurrence and bidirectional tumor dissemination between intraosseous and intraarticular regions. These findings have opened up a new perspective and may provide new targets for intervention in malignant and aggressive tumors around the knee joint.

Bi@Sn Core-Shell Structure with Compressive Strain Boosts the Electroreduction of CO2 into Formic Acid.

As a profitable product from CO2 electroreduction, HCOOH holds economic viability only when the selectivity is higher than 90% with current density (j) over -200.0 mA cm-2. Herein, Bi@Sn core-shell nanoparticles (Bi core and Sn shell, denoted as Bi@Sn NPs) are developed to boost the activity and selectivity of CO2 electroreduction into HCOOH. In an H-cell system with 0.5 m KHCO3 as electrolyte, Bi@Sn NPs exhibit a Faradaic efficiency for HCOOH (FEHCOOH) of 91% with partial j for HCOOH (j HCOOH) of -31.0 mA cm-2 at -1.1 V versus reversible hydrogen electrode. The potential application of Bi@Sn NPs is testified via chronopotentiometric measurements in the flow-cell system with 2.0 m KHCO3 electrolyte. Under this circumstance, Bi@Sn NPs achieve an FEHCOOH of 92% with an energy efficiency of 56% at steady-state j of -250.0 mA cm-2. Theoretical studies indicate that the energy barrier of the potential-limiting step for the formation of HCOOH is decreased owing to the compressive strain in the Sn shell, resulting in the enhanced catalytic performance.

A Highly Efficient Metal-Free Electrocatalyst of F-Doped Porous Carbon toward N2 Electroreduction.

N2 electroreduction into NH3 represents an attractive prospect for N2 utilization. Nevertheless, this process suffers from low Faraday efficiency (FE) and yield rate for NH3 . In this work, a highly efficient metal-free catalyst is developed by introducing F atoms into a 3D porous carbon framework (F-doped carbon) toward N2 electroreduction. At -0.2 V versus reversible hydrogen electrode (RHE), the F-doped carbon achieves the highest FE of 54.8% for NH3 , which is 3.0 times as high as that (18.3%) of pristine carbon frameworks. Notably, at -0.3 V versus RHE, the yield rate of F-doped carbon for NH3 reaches 197.7 µgNH3 mg-1 cat. h-1 . Such a value is more than one order of magnitude higher than those of other metal-free electrocatalysts under the near-ambient conditions for NH3 product to date. Mechanistic studies reveal that the improved performance in N2 electroreduction for F-doped carbon originates from the enhanced binding strength of N2 and the facilitated dissociation of N2 into *N2 H. F bonding to C atom creates a Lewis acid site due to the different electronegativity between the F and C atoms. As such, the repulsive interaction between the Lewis acid site and proton H suppresses the activity of H2 evolution reaction, thus enhancing the selectivity of N2 electroreduction into NH3 .

A first case report of primary epithelial myoepithelial carcinoma-like renal tumor showing a perivascular pseudorosette-like pattern: Description of morphologic, immunohistochemical, and genetic features.

RATIONALE: Over the past decade, although several new entities of renal tumors have emerged, a form of renal cell carcinoma (RCC) that morphologically resembles epithelial-myoepithelial carcinoma has not been reported thus far. Herein, we describe a case of an unusual renal tumor that remained unclassified under a current RCC subtype, and briefly present its morphologic, immunophenotypic, and genetic features. PATIENT CONCERNS: The patient was an 85-year-old man who presented with hematuria and flank pain. Imaging studies revealed a left renal mass without enlarged lymph nodes. There were no abnormal masses or nodules in other organs. DIAGNOSES: The patient underwent no other treatment except the left radical nephrectomy under a clinical diagnosis of invasive urothelial carcinoma and was discharged on the thirteenth day. Histologically, the renal tumor showed biphasic proliferation of epithelial (strongly cytokeratin-positive; P63, P40, and vimentin-negative) and myoepithelial (strongly vimentin-positive; focal P63 and P40-positive; and weakly cytokeratin-positive) cells arranged in a perivascular pseudorosette-like pattern. No mutations were detected in multiple gene tests. According to the pathological structure, the patient was diagnosed as primary epithelial myoepithelial carcinoma-like renal tumor. INTERVENTIONS: To the best of our knowledge, the present tumor has not been previously described, and thus, this variant has not been integrated into a known form of PCC. Therefore, we cannot diagnose this type of tumor with other types of kidney tumors. OUTCOMES: Three years after primary diagnosis, the patient died of multiple organ failure result from multiple distant metastases. LESSONS: We present the first case of carcinoma of the kidney with EMC-like features and a perivascular pseudorosette-like growth pattern. Clinicians should be aware of the features of this uncommon variant of RCC to avoid diagnostic delays or misdiagnosis and prevent unnecessary or inappropriate treatment.

Primary pulmonary hepatoid adenocarcinoma: A case report and review of the literature.

RATIONALE: Hepatoid adenocarcinoma of lung (HAL) is a rare malignant tumor, which can be defined as a primary alpha-fetoprotein (AFP)-producing lung carcinoma. The majority of hepatoid adenocarcinoma (HAC) expressed AFP in tumor cells, but AFP expression is not required for its diagnosis according to the modified diagnostic criteria. Despite that HAC exhibits a poor prognosis and ineffective treatment options, early diagnosis and aggressive treatment can result in long-term survival. PATIENT CONCERNS: We report a 70-year-old Chinese male patient with alcoholic intake over 30 years and smoking history of 60 cigarettes per day for 40 years. He sought medical consultation for productive cough and hemoptysis sputum. DIAGNOSES AND INTERVENTIONS: Chest CT scan revealed a mass (6.4 × 5.5 cm) in the left lower lobe of the lung. The patient underwent curative surgical resection, and subsequently diagnosed as HAL. OUTCOMES: Eighteen months after primary diagnosis, the patient died of multiple organ failure caused by distant metastases. LESSONS: Familiarizing with the clinical features and modified diagnostic criteria of this rare tumor may increase awareness of the disease among clinicians and pathologists, thereby avoiding misdiagnosis and mistreatment.

SOX4 is overexpressed in diffusely infiltrating astrocytoma and confers poor prognosis.

The SOX4 (sex-determining region Y-related high-mobility-group box transcription factor 4) gene plays critical roles in embryonic development and cell-fate determination. Recently, SOX4 overexpression has been found in various tumors. However, its expression status and prognostic significance in astrocytoma remain unknown. In this study, SOX4 expression in diffusely infiltrating astrocytoma (WHO grades II-IV) tissues (in comparison with pilocytic astrocytomas) was examined by immunohistochemistry, and its relevance with prognosis was analyzed. Our data showed that SOX4 was over-expressed in diffusely infiltrating astrocytomas and its expression was positively correlated with astrocytoma grade (WHO grades II-IV). Significantly, Kaplan-Meier analysis revealed that SOX4 nuclear overexpression (SOX4-N) was associated with poorer progression-free survival (PFS) and disease-specific survival (DSS) in diffusely infiltrating astrocytoma patients (P < 0.05). Cox regression analysis further showed that nuclear SOX4-N was a significant independent negative prognostic factor for these patients.

[The expression and function of anti-apoptotic Bfl-1 in prostate cancer].

OBJECTIVE: To determine the expression of Bcl2 related protein A1(Bfl-1) mRNA in prostate cancer cell lines and tissues, and to explore the functions of Bfl-1 in prostate adenocarcinoma. METHODS: RT-PCR, real-time quantitative PCR (Q-PCR)and in situ hybridization (ISH) were used to detect the expression of Bfl-1 mRNA in prostate cancer cell lines, tissues and benign prostate hyperplasia (BPH) tissue samples. The relationship between Bfl-1 expression and clinicopathological parameters was analyzed. Antisense oligonucleotides (ASONs) were used to interfere the expression of Bfl-1 and its effects on prostate cancer cells. MTT was used to detect the survival, morphologic changes of prostate cancer cells was observed by inverted microscope. RESULTS: Bfl-1 mRNA, detected by RT-PCR, Q-PCR and ISH, was overexpressed in the androgen-independent prostate cancer cell lines PC-3 and DU145, but not detectable in the androgen-dependent prostate cancer cell line LNCaP and BPH tissue samples (P < 0.05). Significantly higher Bfl-1 mRNA levels were observed in higher stage and metastatic prostate cancer cases than those without metastasis or of low stage. ASONs targeting Bfl-1 significantly inhibited androgen-independent prostate cancer cell growth (P < 0.05), cell was rounding off or fragmentation. CONCLUSION: Bfl-1 is involved in maintaining the hormone-independent prostate cancer cell growth. Bfl-1 may become a new therapeutic target in advanced prostate cancer.

Synergistic silencing by promoter methylation and reduced AP-2α transactivation of the proapoptotic HRK gene confers apoptosis resistance and enhanced tumor growth.

The Harakiri (HRK) gene encodes an important proapoptotic mitochondrial protein of the Bcl-2 family. HRK is expressed in normal tissues but is decreased in many cancers such as melanoma, the mechanisms of which have not been fully elucidated. Here, we demonstrate that HRK is silenced by hypermethylation of a major proximal CpG island in the HRK promoter. Furthermore, we show that HRK is a novel target gene regulated by the transcription factor AP-2α, which interacts with an AP-2α binding site in the HRK promoter. Hypermethylation of the major proximal CpG island (which contains the AP-2α binding site within the most densely methylated -218- to -194-bp region) inhibited AP-2α binding and transcriptional activity. Artificial overexpression of AP-2α in melanoma cells up-regulated HRK transcription, which was further restored by treatment with DNA methyltransferase inhibitor 5-azacytidine. Artificial overexpression of HRK by recombinant adenovirus induced caspase-dependent apoptosis, inhibited melanoma cell growth in vitro, and markedly reduced in vivo melanoma growth in a nude mouse xenograft model. RNA interference by siHRK or siAP-2α reversed the above effects. We conclude that the synergistic effects of HRK promoter hypermethylation and loss of AP-2α transactivation lead to HRK gene silencing and confer resistance to apoptosis and enhanced tumor growth. These novel molecular lesions may provide the basis for new therapeutic approaches to treating AP-2α- and HRK-deficient cancers.