Role of the Nrf2 Signaling Pathway in Ovarian Aging: Potential Mechanism and Protective Strategies.

The ovary holds a significant role as a reproductive endocrine organ in women, and its aging process bears implications such as menopause, decreased fertility, and long-term health risks including osteoporosis, cardiovascular disorders, and cognitive decline. The phenomenon of oxidative stress is tightly linked to the aging metabolic processes. More and more studies have demonstrated that oxidative stress impacts both physiologic and pathologic ovarian aging, and the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway plays a crucial role in regulating the antioxidant response. Furthermore, various therapeutic approaches have been identified to ameliorate ovarian aging by modulating the Nrf2 pathway. This review summarizes the important role of the Nrf2/ Kelch-like ECH-associated protein 1 (Keap1) signaling pathway in regulating oxidative stress and influencing ovarian aging. Additionally, it highlights the therapeutic strategies aimed at targeting the Nrf2/Keap1 pathway.

Tumor microenvironment promotes lymphatic metastasis of cervical cancer: its mechanisms and clinical implications.

Although previous studies have shed light on the etiology of cervical cancer, metastasis of advanced cervical cancer remains the main reason for the poor outcome and high cancer-related mortality rate. Cervical cancer cells closely communicate with immune cells recruited to the tumor microenvironment (TME), such as lymphocytes, tumor-associated macrophages, and myeloid-derived suppressor cells. The crosstalk between tumors and immune cells has been clearly shown to foster metastatic dissemination. Therefore, unraveling the mechanisms of tumor metastasis is crucial to develop more effective therapies. In this review, we interpret several characteristics of the TME that promote the lymphatic metastasis of cervical cancer, such as immune suppression and premetastatic niche formation. Furthermore, we summarize the complex interactions between tumor cells and immune cells within the TME, as well as potential therapeutic strategies to target the TME.

The progress of radiomics in thyroid nodules.

Due to the development of Artificial Intelligence (AI), Machine Learning (ML), and the improvement of medical imaging equipment, radiomics has become a popular research in recent years. Radiomics can obtain various quantitative features from medical images, highlighting the invisible image traits and significantly enhancing the ability of medical imaging identification and prediction. The literature indicates that radiomics has a high potential in identifying and predicting thyroid nodules. So in this article, we explain the development, definition, and workflow of radiomics. And then, we summarize the applications of various imaging techniques in identifying benign and malignant thyroid nodules, predicting invasiveness and metastasis of thyroid lymph nodes, forecasting the prognosis of thyroid malignancies, and some new advances in molecular level and deep learning. The shortcomings of this technique are also summarized, and future development prospects are provided.

Primary cesarean scar choriocarcinoma: A case series and literature review.

OBJECTIVES: To provide clinical guidance for early diagnosis and effective management of primary cesarean scar choriocarcinoma, which is an extremely rare but highly malignant trophoblastic tumor. METHODS: This retrospective case series summarized the clinical courses of seven patients diagnosed with cesarean scar choriocarcinoma. RESULTS: We identified two patients in our institution with cesarean scar choriocarcinoma. In addition, details of the previous five patients were extracted from databases and analyzed to provide more clinical information. The seven patients had an average age of 31.14 years, their tumor sizes ranged from 2.0 to 6.5 cm, and their pretreatment serum ß-human chorionic gonadotropin (ß-hCG) levels ranged from 3664 to 312 468 mIU/mL. All the patients were categorized as having FIGO Stage I disease, with four patients at low risk and three at high risk. Six of the seven were misdiagnosed with ectopic pregnancy before pathologic examination. CONCLUSIONS: Clinicians should pay attention to masses in cesarean scar and to continuous elevation of serum ß-hCG levels after treatment. When cesarean scar choriocarcinoma is suspected, diagnostic surgery can be chosen for tentative treatment and pathologic sampling. Salvage EMA-CO chemotherapy (etoposide, actinomycin D, methotrexate, cyclophosphamide and vincristine) should be performed as early as possible to prevent metastasis and recurrence after pathologic diagnosis.

Progress in diagnosing and treating thyroid squamous cell carcinoma under the 5th edition of WHO classification.

Squamous cell carcinoma of the thyroid (SCCT) is a rare thyroid gland malignancy, with only a few hundred cases reported in the literature, mostly as case reports or small sample studies. In the previous WHO classification, squamous cell carcinoma of the thyroid was defined as a carcinoma composed entirely of squamous cells without differentiated carcinoma components. It was once included in the WHO tumor classification separately. However, the 2022 WHO classification of squamous cell carcinoma of the thyroid was reclassified as a morphologic subtype of anaplastic thyroid carcinoma (ATC). The squamous cell carcinoma pattern is similar to the other histologic types of ATC, but the phenotype associated has a poorer prognosis. The typical clinical manifestation of this condition is a cervical mass, accompanied by indications and symptoms of compression on adjacent structures such as the esophagus and trachea in advanced stages. Secondary squamous cell carcinoma of the thyroid may occur due to the spread of squamous carcinoma of the larynx or esophagus or distant metastases from other sites. Diagnosis of squamous cell carcinoma of the thyroid includes neck Ultrasound (US), Computed Tomography (CT) or Magnetic Resonance Imaging (MRI), puncture tissue biopsy, and full endoscopy to identify metastatic lesions from the nasopharynx, oropharynx, hypopharynx, larynx, esophagus, or bronchi and to help with the initial staging of the tumor. Current treatment modalities include surgery, radiotherapy, chemotherapy, or a combination. Because of the poor prognosis of patients with this disease, the short survival period, usually less than one year, and the difficulty of preoperative diagnosis, this article reviews the epidemiological features, origin, clinical features, pathological features, and differential diagnosis to improve the diagnosis and treatment of this disease by clinicians.

Global burden and trends of pelvic organ prolapse associated with aging women: An observational trend study from 1990 to 2019.

Purpose: Worldwide, about 40% of women will experience pelvic organ prolapse (POP), and this proportion is expected to increase with the aging of the population. We investigated the global, regional and national influenza burden in the past 30 years through the age and sociodemographic index (SDI). Patients and methods: Data were extracted from the Global Burden of Disease (GBD) 2019 database for 195 countries and territories between 1990 and 2019. Estimated annual percentage changes (EAPCs) were used to explore the age-standardized incidence rate (ASIR) and age-standardized disability adjusted life years (AS-DALYs) trends, and the corresponding 95% uncertainty intervals (UI). In addition, the time cut-off points of 1990 and 2019 were used to separately analyze the incidence rate and DALYs. Results: In 2019, the global ASIR and AS-DALYs for POP were 316.19 (95%UI: 259.84-381.84) and 10.37 (95%UI: 5.79-17.99) per 100,000 population, respectively. Moreover, from 1990 to 2019, the ASR of both showed a downward trend, and EAPCs were -0.46 (95%CI: -0.52 to -0.4) and -0.53 (95%CI: -0.58 to -0.47), respectively. In addition, DALYs of POP also showed a downward trend in most regions and countries with high SDI. From 1990 to 2019, the global incidence rate and DALYs rate were highest in the 65-75 and ≥60 age groups, respectively. Conclusion: Over the past three decades, the incidence and DALY of POP have been decreasing from 1990 to 2019. However, POP remains a major health problem, especially among females in less developed countries. Primary and secondary prevention measures of POP should be integrated into the practice of healthcare professionals dealing with aging women.

Recent Progress in Second Near-Infrared (NIR-II) Fluorescence Imaging in Cancer.

Cancer continues to be one of the leading causes of death worldwide, and its incidence is on the rise. Although cancer diagnosis and therapy have advanced significantly in recent decades, it is still a challenge to achieve the accurate identification and localization of cancer and to complete tumor elimination with a maximum preservation of normal tissue. Recently, second near-infrared region (NIR-II, 1000-1700 nm) fluorescence has shown great application potential in cancer theranostics due to its inherent advantages, such as great penetration capacity, minimal tissue absorption and scattering, and low autofluorescence. With the development of fluorescence imaging systems and fluorescent probes, tumor detection, margin definition, and individualized therapy can be achieved quickly, enabling an increasingly accurate diagnosis and treatment of cancer. Herein, this review introduces the role of NIR-II fluorescence imaging in cancer diagnosis and summarizes the representative applications of NIR-II image-guided treatment in cancer therapy. Ultimately, we discuss the present challenges and future perspectives on fluorescence imaging in the field of cancer theranostics and put forward our opinions on how to improve the accuracy and efficiency of cancer diagnosis and therapeutics.

Development of a new chemo-enzymatic catalytic route for synthesis of (S)- 2-chlorophenylglycine.

(S)-2-chlorophenylglycine ((S)-CPG) is a key chiral intermediate for the synthesis of clopidogrel. Herein, a novel, efficient and environmentally friendly chemo-enzymatic route for the preparation of optically pure (S)-CPG was developed. A straightforward chemical synthesis of the corresponding prochiral keto acid substrate (2-chlorophenyl)glyoxylic acid (CPGA) was developed with 91.7% yield, which was enantioselectively aminated by leucine dehydrogenase (LeuDH) to (S)-CPG. Moreover, protein engineering of LeuDH was performed via directed evolution and semi-rational design. A beneficial variant EsLeuDH-F362L with enlarged substrate-binding pocket and increased hydrogen bond between K77 and substrate CPGA was constructed, which exhibited 2.1-fold enhanced specific activity but decreased thermal stability. Coupled with a glucose dehydrogenase from Bacillus megaterium (BmGDH) for NADH regeneration, EsLeuDH-F362L completely converted up to 0.5 M CPGA to (S)-CPG in 8 h at 40 °C.

Tuning enzymatic properties by protein engineering toward catalytic tetrad of carbonyl reductase.

Enzyme engineering toward catalytic-tetrad residues usually results in activity loss. Unexpectedly, we found that a directed evolution campaign yielded a beneficial residue A100 in KmCR (a carbonyl reductase from Kluyveromyces marxianus ZJB14056), which is a residue of catalytic tetrad and conserved according to multiple sequence alignment. Inspired by this finding, we performed saturation mutagenesis on all the four residues of catalytic tetrad of KmCR. A number of variants with improved enzymatic activities were obtained. Among them, the variant KmCR_A100S exhibited increased catalytic efficiency (kcat /KM = 47.3 s-1 ·mM-1 ), improved stereoselectivity (from moderate selectivity (deP = 66.7%) to strict (S)-selectivity (deP > 99.5%)), and extended substrate scope, compared to those of KmCR_WT. In silico analysis showed that a relay system was rebuilt in KmCR via the beneficial residue S100. Furthermore, comparison of 11 protein engineering campaigns indicated that the beneficial position is easily overlooked due to the long distance (>10 Å) from ketone substrates. Since CRs share similar catalytic mechanism, the knowledge gained from this study has universal significance to CR engineering.

Astaxanthin protects spinal cord tissues from apoptosis after spinal cord injury in rats.

BACKGROUND: There is emerging evidence that astaxanthin plays a significant role in protecting neuro-cells from apoptosis after central nervous system injury. Our study examined the effects of astaxanthin on neuro-cell apoptosis after spinal cord injury. METHODS: One hundred and forty-four healthy adult Sprague-Dawley rats were randomly divided into the experimental group, control group, and sham operation group (n=48). Spinal cord injury was induced using the modified Allen method in the control group and the experimental group; while in the sham operation group, the lamina was removed without spinal cord injury. The rats in the experimental group were given astaxanthin (75 mg/kg) by gavage immediately after the operation, and in the other groups were given the same amount of olive oil. Motor function was assessed by blood-brain barrier (BBB) scores. The malondialdehyde (MDA) content and the activity of superoxide dismutase (SOD) at 24 h was determined after the operation. The apoptosis index (AI) was determined at 6, 24, and 48 h after the operation. At 48 h after the operation, we calculated the water content of the spinal cord, the lesion ratio of the spinal cord, the ultrastructure of the spinal cord, and the ultrastructure score. RESULTS: The BBB scores of the control and experimental groups were significantly lower than the sham operation group at each postoperative time (P<0.05), and the BBB score of the experimental group was significantly higher than the control group at 1-4 weeks postoperatively (P<0.05). At 24 hours postoperatively, MDA content was highest in the control group and lowest in the sham operation group, while SOD activity was highest in the sham operation group and lowest in the control group (P<0.05). At each time point postoperatively, the sham operation group had the lowest AI and the control group had the highest AI (P<0.05). At 48 h after the operation, the water content and the lesion ratio of the spinal cord, and the ultrastructure score were the lowest in the sham operation group and the highest in the control group (P<0.05). CONCLUSIONS: Astaxanthin significantly improved the motor function of rats with spinal cord injury.

Pickled egg production: effect of brine acetic acid concentration and packing conditions on acidification rate.

U.S. federal regulations require that acidified foods must reach a pH of 4.6 or lower within 24 h of packaging or be kept refrigerated until then. Processes and formulations should be designed to satisfy this requirement, unless proper studies demonstrate the safety of other conditions. Our objective was to determine the effect of brine acetic acid concentration and packing conditions on the acidification rate of hard-boiled eggs. Eggs were acidified (60/40 egg-to-brine ratio) at various conditions of brine temperature, heat treatment to filled jars, and postpacking temperature: (i) 25 °C/none/25 °C (cold fill), (ii) 25 °C/none/2 °C (cold fill/refrigerated), (iii) 85 °C/none/25 °C (hot fill), and (iv) 25 °C/100 °C for 16 min/25 °C (water bath). Three brine concentrations were evaluated (7.5, 4.9, and 2.5% acetic acid) and egg pH values (whole, yolk, four points within egg) were measured from 4 to 144 h, with eggs equilibrating at pH 3.8, 4.0, and 4.3, respectively. Experiments were conducted in triplicate, and effects were considered significant when P < 0.05. Multiple linear regression analysis was conducted to evaluate the effect on pH values at the center of the yolk. Regression analysis showed that brine concentration of 2.5% decreased the acidification rate, while packing conditions of the hot fill trial increased it. Inverse prediction was used to determine the time for the center of the yolk and the total yolk to reach a pH value of 4.6. These results demonstrate the importance of conducting acidification studies with proper pH measurements to determine safe conditions to manufacture commercially stable pickled eggs.