(+)-Borneol, the main component of "Natural Borneol" in the Chinese Pharmacopoeia, is a high-end spice and precious medicine. Plant extraction cannot meet the increasing demand for (+)-borneol, while microbial biosynthesis offers a sustainable supply route. However, its production was extremely low compared with other monoterpenes, even with extensively optimizing the mevalonate pathway. We found that the key challenge is the complex and unusual dephosphorylation reaction of bornyl diphosphate (BPP), which suffers the side-reaction and the competition from the cellular dephosphorylation process, especially lipid metabolism, thus limiting (+)-borneol synthesis. Here, we systematically optimized the dephosphorylation process by identifying, characterizing phosphatases, and balancing cellular dephosphorylation metabolism. For the first time, we identified two endogenous phosphatases and seven heterologous phosphatases, which significantly increased (+)-borneol production by up to 152%. By engineering BPP dephosphorylation and optimizing the MVA pathway, the production of (+)-borneol was increased by 33.8-fold, which enabled the production of 753 mg/L under fed-batch fermentation in shake flasks, so far the highest reported in the literature. This study showed that rewiring dephosphorylation metabolism was essential for high-level production of (+)-borneol in Saccharomyces cerevisiae, and balancing cellular dephosphorylation is also helpful for efficient biosynthesis of other terpenoids since all whose biosynthesis involves the dephosphorylation procedure.

[This corrects the article DOI: 10.1016/j.apsb.2024.03.030.].

With the advent of precision medicine and personalized treatment, targeted therapies have become pivotal in oncology. Noninvasive molecular imaging, especially immunoPET/SPECT, plays a crucial role in refining cancer diagnostics and treatment monitoring by visualizing biological processes at the molecular level. This review explores the dynamic field of immunoPET/SPECT imaging using Fab and F(ab')₂ fragments, characterized by advantageous pharmacokinetics and swift clearance from the bloodstream, making them suitable for same-day imaging procedures. We examine contemporary strategies for radiolabeling these fragments with PET and SPECT radionuclides and discuss potential advancements and the challenges anticipated in the further development of Fab and F(ab')₂ fragments. Despite the complexities involved in their development, these fragments hold significant promise for advanceing personalized cancer treatment. Keys to this advancement are innovative radiolabeling techniques, site-specific conjugation chemistries, and short-lived radionuclides, all of which are crucial for overcoming existing limitations and enhancing the clinical utility of these imaging agents. As research progresses, Fab and F(ab')₂ fragments are expected to become central to the future of cancer diagnostics and therapeutic monitoring, thereby improving patient management and contributing significantly to the evolution of personalized medicine.

Humans ; Breast ; Neoplasms, Muscle Tissue/surgery*

Humans ; Stomach Neoplasms/pathology*

Humans ; Ulcer/pathology* ; Herpesvirus 4, Human ; Epstein-Barr Virus Infections ; Skin Diseases

Objective: To investigate the clinicopathological characteristics of occupational lung diseases, to reduce the missed diagnoses and misdiagnoses of the diseases and to help standardize the diagnosis and treatment of these patients. Methods: A total of 4 813 lung biopsy specimens (including 1 935 consultation cases) collected at the Department of Pathology, Nanjing Drum Tower Hospital, Nanjing, China from January 1st, 2017 to December 31th, 2019 were retrospectively analyzed. Among them, 126 cases of occupational lung diseases were confirmed with clinical-radiological-pathological diagnosis. Special staining, PCR and scanning electron microscopy were also used to rule out the major differential diagnoses. Results: The 126 patients with occupational lung diseases included 102 males and 24 females. All of them had a history of exposure to occupational risk factor(s). Morphologically, 68.3% (86/126) of the cases mainly showed pulmonary fibrotic nodules, dust plaque formation or carbon end deposition in pulmonary parenchyma. 16.7% (21/126) of the cases mainly showed welding smoke particle deposition in the alveolar cavity and lung interstitium while 15.1% (19/126) of the cases showed granulomas with fibrous tissue hyperplasia, alveolar protein deposition or giant cell interstitial pneumonia. The qualitative and semi-quantitative analyses of residual dust components in the lung under scanning electron microscope were helpful for the diagnosis of welder's pneumoconiosis and hard metal lung disease. Conclusions: The morphological characteristics of lung biopsy tissue are important reference basis for the clinicopathological diagnosis and differential diagnosis of occupational lung diseases. Recognizing the characteristic morphology and proper use of auxiliary examination are the key to an accurate diagnosis of occupational lung diseases on biopsy specimens.
Male ; Female ; Humans ; Retrospective Studies ; Pneumoconiosis/pathology* ; Lung/pathology* ; Dust ; Pneumonia, Viral/pathology* ; Biopsy

Objective: To investigate the clinicopathologic features of progressively transformed germinal center-like follicular T-cell lymphoma (PTGC-like FTCL). Methods: The clinicopathologic data of 14 PTGC-like FTCL cases that were diagnosed at the Beijing Friendship Hospital Affiliated to the Capital Medical University from January 2017 to January 2022 were retrospectively collected. Clinicopathological features, immunophenotype, and Epstein-Barr virus (EBV) infection status were analyzed in these cases. Polymerase chain reaction (PCR) was performed to detect the clonal gene rearrangements of T cell receptor (TCR) and the immunoglobulin (Ig) in 10 and 8 cases, respectively. Results: The male to female ratio was 5∶2. The median age was 61 years (range 32-70 years). All patients had lymphadenopathy at the time of diagnosis. By using the Ann Arbor system staging, seven cases were classified as stage Ⅰ-Ⅱ, and seven cases as stage Ⅲ-Ⅳ. Seven cases had B symptoms, four cases had splenomegaly, and two cases had skin rash and pruritus. Previously, three cases were diagnosed as classic Hodgkin's lymphoma, three cases as small B-cell lymphoma, two cases as atypical lymphoid hyperplasia unable to exclude angioimmunoblastic T-cell lymphoma (AITL), one case as EBV-associated lymphoproliferative disorder, and one case as peripheral T-cell lymphoma (PTCL) associated with the proliferation of B cells. All the 14 cases showed that the large nodules were composed of mature CD20+, IgD+B lymphocytes admixed with small aggregates of neoplastic cells with pale to clear cytoplasm. Moreover, hyperplastic germinal centers (GCs) and Hodgkin/Reed-Sternberg-like (HRS-like) cells were seen within these nodules in two and five cases, respectively. The neoplastic cells expressed CD3 (14/14), CD4 (14/14), PD1 (14/14), ICOS (14/14), CD10 (9/14), bcl-6 (12/14), CXCL13 (10/14), and CD30 (10/14). The HRS-like cells in five cases expressed CD20 (2/5), PAX5 (5/5), CD30 (5/5), CD15 (2/5), LCA (0/5), OCT2 (5/5) and BOB1 (2/5). Moreover, neoplastic T cells formed rosettes around HRS-like cells. EBV-encoded RNA (EBER) in situ hybridization showed scattered, small, positive bystander B lymphocytes in 8/14 cases, including 3/5 cases containing HRS-like cells. All tested cases (including five with HRS-like cells) showed monoclonal TCR gene rearrangement and polyclonal Ig gene rearrangement. Conclusions: PTGC-like FTCL is a rare tumor originated from T-follicular helper cells. It could be distinguished from angioimmunoblastic T-cell lymphoma by the formation of follicular structure, and lack of follicular dendritic cell proliferation outside the follicles and the polymorphous inflammatory background. In addition, it should be differentiated from lymphocyte-rich classical Hodgkin's lymphoma and low-grade B cell lymphoma.
Humans ; Male ; Female ; Adult ; Middle Aged ; Aged ; Lymphoma, T-Cell, Peripheral/pathology* ; Reed-Sternberg Cells/pathology* ; Epstein-Barr Virus Infections ; Hyperplasia/pathology* ; Retrospective Studies ; Herpesvirus 4, Human/genetics* ; Immunoblastic Lymphadenopathy/pathology* ; Hodgkin Disease/pathology* ; Germinal Center/pathology* ; Receptors, Antigen, T-Cell

Male ; Humans ; Prostatic Neoplasms ; Cell Line, Tumor ; Cell Differentiation ; Carcinoma, Neuroendocrine

OBJECTIVE: To investigate the spatial distribution characteristics of the prevalence of advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody, and to examine the correlation between the prevalence of advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody in Hunan Province in 2020, so as to provide insights into advanced schistosomiais control in the province. METHODS: The epidemiological data of schistosomiasis in Hunan Province in 2020 were collected, including number of permanent residents in survey villages, number of advanced schistosomiasis patients, number of residents receiving serological tests and number of residents seropositive for anti-Schistosoma antibody, and the prevalence advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody were descriptively analyzed. Village-based spatial distribution characteristics of prevalence advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody were identified in Hunan Province in 2020, and the correlation between the revalence advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody was examined using Spearman correlation analysis. RESULTS: The prevalence of advanced schistosomiasis was 0 to 2.72% and the seroprevalence of anti-Schistosoma antibody was 0 to 20.25% in 1 153 schistosomiasis-endemic villages in Hunan Province in 2020. Spatial clusters were identified in both the prevalence of advanced schistosomiasis (global Moran's I = 0.416, P < 0.01) and the seroprevalence of anti-Schistosoma antibody (global Moran's I = 0.711, P < 0.01) in Hunan Province. Local spatial autocorrelation analysis identified 98 schistosomiasis-endemic villages with high-high clusters of the prevalence of advanced schistosomiasis, 134 endemic villages with high-high clusters of the seroprevalence of anti-Schistosoma antibody and 36 endemic villages with high-high clusters of both the prevalence of advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody in Hunan Province. In addition, spearman correlation analysis showed a positive correlation between the prevalence of advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody (r_s = 0.235, P < 0.05). CONCLUSIONS There were spatial clusters of the prevalence of advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody in Hunan Province in 2020, which were predominantly located in areas neighboring the Dongting Lake. These clusters should be given a high priority in the schistosomiasis control programs.
Animals ; Humans ; Prevalence ; Seroepidemiologic Studies ; Schistosomiasis/epidemiology* ; Schistosoma ; Spatial Analysis ; Antibodies, Helminth ; China/epidemiology*