The acute toxic effect of Chinese medicine Fuzi is exacerbated in kidney yang deficiency mice due to metabolic difference.

ETHNOPHARMACOLOGICAL RELEVANCE: The proper application of toxic medicines is one of the characteristics of traditional Chinese medicines, and the use of traditional Chinese medicines follows the principle of dialectical treatment. It is necessary to combine different "syndrome" or "disease" states with the toxicity of traditional Chinese medicines to form a reliable toxicity evaluation system. Fuzi, the lateral root of Aconitum carmichaelii Debx, is recognized as a panacea for kidney yang deficiency syndrome, however, its toxic effects significantly limit its clinical application. AIM OF THE STUDY: Herein, our research aimed to explore the toxic effects of Fuzi on syndrome models, and tried to reveal the underlying mechanisms. MATERIALS AND METHODS: Firstly, the mouse model of kidney yang deficiency syndrome was established through intramuscular injection of 25 mg/kg hydrocortisone per day for 10 consecutive days. Then, the acute toxicity of Fuzi in normal mice and kidney yang deficiency model mice was explored. Finally, the plasma metabolite concentrations and liver CYP3A4 enzyme activity were analyzed to reveal the possible mechanisms of the different pharmacological and toxicological effects of Fuzi in individuals with different physical constitutions. RESULTS: It was found that the treatment with Fuzi (138 g/kg) had serious toxic effects on kidney yang deficiency mice, leading to the death of 80% of the mice, whereas it showed no lethal toxicity in normal mice. This indicates that Fuzi induced greater toxicity in kidney yang deficiency mice than in normal ones. The liver CYP3A4 enzyme activity in kidney yang deficiency mice was decreased by 20% compared to the controls, resulting in slower metabolism of the toxic diester diterpenoid alkaloids in Fuzi. CONCLUSION: In conclusion, our study showed that changes of the metabolic enzyme activity in individuals with different syndromes led to different toxic effects of Chinese medicines, emphasizing the crucial importance of considering individual physical syndromes in the clinical application of traditional Chinese medicine, and the significance of conducting safety evaluations and dose predictions on animal models with specific syndromes for traditional Chinese medicines.

Discovery of novel dual Bruton's tyrosine kinase (BTK) and Janus kinase 3 (JAK3) inhibitors as a promising strategy for rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronically systemic autoimmune disorder, which is related with various cellular signal pathways. Both BTK (Bruton's Tyrosine Kinase) and JAK3 (Janus Kinase 3) play important roles in the pathogenesis of rheumatoid arthritis. Herein, we reported the discovery of dual BTK/JAK3 inhibitors through bioisosterism and computer-aided drug design based on the structure of BTK inhibitor ibrutinib. We reported the discovery of dual BTK/JAK3 inhibitors which are based on the structure of BTK inhibitor ibrutinib via the method of bioisosterism and computer-aided drug design) Most of the target compounds exhibited moderate to strong inhibitory activities against BTK and JAK3. Among them, compound XL-12 stood out as the most promising candidate targeting BTK and JAK3 with potent inhibitory activities (IC50 = 2.0 nM and IC50 = 14.0 nM respectively). In the in vivo studies, compound XL-12 (40 mg/kg) exhibited more potent antiarthritic activity than ibrutinib (10 mg/kg) in adjuvant arthritis (AA) rat model. Furthermore, compound XL-12 (LD50 > 1600 mg/kg) exerted improved safety compared with ibrutinib (LD50 = 750 mg/kg). These results indicated that compound XL-12, the dual BTK/JAK3 inhibitor, might be a potent drug candidate for the treatment of RA.

[Distribution, hazard evaluation, and control measures of allergenic airborne pollen]. / è‡´æ•æ€§æ°”ä¼ èŠ±ç²‰çš„åˆ†å¸ƒã€å±å®³è¯„ä»·åŠé˜²æ²»æŽªæ–½.

Allergenic airborne pollen can induce hay fever such as rhinitis and asthma. Many studies have been conducted on the allergenic pollution caused by airborne pollen. We synthesized available studies to summarize the temporal and spatial distributions of airborne pollen and influencing meteorological factors. We further summarized and discussed the hazards of airborne pollen sensitization on human health and evaluation indicators for classifying hazard levels. We described the research progress of prevention and control measures of airborne pollen induced pollution from the perspectives of source control, route monitoring, and prevention of susceptible population. Considering the limitations of current studies, we proposed some research directions on allergenic airborne pollen. The types of allergenic plants needed to be clearly identified and allergentic potential should be quantitatively identified. The methods of pollen collection and concentration monitoring needed to be improved and standardized. This review could provide a scientific guidance for the study on preventing and treating pollen allergies as well as optimizing urban green space planning.

[Analysis on the Current Situation of Phytoplankton in the Typical River-Lake Ecotone of Lake Poyang].

The typical river-lake ecotone (tail end area) of Poyang Lake, which is a sensitive area and prone to outbreaks of cyanobacteria bloom, is vulnerable to frequent human activities. To explore the diversity of phytoplankton community structure and the relevant driving mechanism in the typical river lake junction area of Poyang Lake, the water quality and phytoplankton at seven sampling points in the typical river lake junction area of Poyang Lake, at six sampling points in the middle section of Poyang Lake River, and at one sampling point in the main lake area were investigated in the field from 2019 to 2020 (dry season), April (flood season), July (wet season), and October (recession period). The results showed that there were seven phyla and 64 genera of phytoplankton in the typical river-lake ecotone of Poyang Lake, and the biomass and relative abundance of phytoplankton were dominated by diatoms and cyanobacteria. The biomass and abundance in the east of the typical river-lake ecotone of Poyang Lake were generally higher than those in the west, and the biomass and abundance in the river-lake ecotone were higher than those in the middle of the river. The dominant degree of cyanobacteria in the lake area and the river-lake ecotone was large, and the dominant degree of diatoms in the middle section of the river was large. The Monte Carlo test results showed that total nitrogen (TN), total phosphorus (TP), orthophosphate phosphorus (PO43--P), water depth (WD), water temperature (WT), and transparency (SD) were significantly related environmental factors affecting the distribution of the phytoplankton community. Redundancy analysis results showed that the typical river-lake ecotone in the west of Poyang Lake was highly affected by the hydration factors (TN, TP, and PO43--P), and the hydrological factors (WT, WD, and SD) in the typical river-lake ecotone in the east were highly significant. The impact factors of phytoplankton in the typical river-lake ecotone of Poyang Lake were seasonal, being greatly affected by hydration factors in winter and hydrological factors in summer.

Pore Structure Characterizations of Shale Oil Reservoirs with Heat Treatment: A Case Study from Dongying Sag, Bohai Bay Basin, China.

Heat treatment plays a significant role in determining the petrophysical properties of shale reservoirs; however, the existing studies on the evolution of pore structures are still insufficient. This study conducts a series of tests, including Rock-Eval, low-temperature nitrogen adsorption-desorption, nuclear magnetic resonance (NMR) T2, and T1-T2 tests on samples from Shahejie Formation, Dongying Sag, Bohai Bay Basin. The tests aim to determine the changes in the shale pore structures under increasing heat treatments (ranging from 110 to 500 °C) and identify the factors that control pore structures. The results show that the gradual decomposition of organic matter leads to an eventual decrease in the total organic carbon (TOC) content. The decrease in TOC is more prominent when the temperature exceeds 300 °C. For shales with lower TOC contents (<2%), the Brunauer-Emmett-Teller specific surface area (BET SSA) first decreases, then increases, but eventually decreases again. However, the average pore diameter demonstrates an opposite trend when the temperature increases. In contrast, for organic-rich shales (TOC > 2%), the BET SSA increases at temperatures above 200 °C. The similarity between the D1 values implies that the complexity and heterogeneity of shale pore surface only undergo minor changes during heat treatment. Porosity shows an increasing trend, and the higher the contents of clay minerals and organic matter in shales are, the greater the change in porosity is. The NMR T2 spectra suggest that micropores (<0.1 µm) in shales first decrease and then increase, whereas the contents of meso- (0.1-1 µm) and macropores (>1 µm) increase, corresponding to the increase in free shale oil. Moreover, shale pore structures are primarily controlled by clay minerals and organic matter contents during heat treatments, with higher contents resulting in better pore structures. Overall, this study contributes to detailing the shale pore structure characteristics during the in situ conversion process (ICP).

The Efficacy of Volumetric Modulated Arc Therapy Combined With Chemotherapy, Brachytherapy, and Local Hyperthermia on Patients with Locally Advanced Cervical Cancer: A Retrospective Study.

OBJECTIVE: To evaluate the clinical outcomes of volumetric modulated arc therapy (VMAT) followed by brachytherapy (BT), combined with chemotherapy, and local hyperthermia (HT) on locally advanced cervical cancer (LACC). METHODS: In total, 40 patients with FIGO stage IB1-IVB cervical cancer from January 2016 to December 2018 were selectively enrolled in this study. All patients were treated with VMAT (50.4 Gy/1.8 Gy/28 f) concurrent with cisplatin-based chemotherapy (40 mg/m2, q1w, 6 cycles) and local HT (40.5-41°C for 60 min, BIW). BT (30-36 y/5-6 f, 2 f/w) was conducted after VMAT. Objective response rate (ORR), local control (LC) time, LC rate, progression-free survival (PFS) rate, cancer-specific survival (CSS) rate, overall survival (OS), median time to tumor progression and treatment-related toxicity were evaluated. RESULTS: The median follow-up time was 31 months (8-48). The ORR was 100% at 3 months after treatment and 92.1% at 6 months, respectively. The 1-year, 2-year, and 3-year LC rates were 87.4%, 81.9%, and 70.9%, respectively. The average LC time was 31.50 ± 1.89 months (95% CI 27.79-35.21). The 1-year, 2-year, and 3-year PFS rates were 75.85%, 61.2%, and 51.3%, respectively, while the median PFS was 27.07 months. The 1-year, 2-year, and 3-year OS rates were 95%, 84%, and 79.6%, respectively. In total, 12(30%) patients had grade 3/4 bone marrow suppression. One patient had grade 4 leukopenia. In total, 17 patients had grade 1/2 bone marrow suppression. Two patients had grade 3 nausea and grade 3 vomiting reaction, respectively. No grade 3/4 proctitis and bladder reaction were observed. In the late period of treatment, 1 patient had a rectal hemorrhage. In total, 13 patients had vaginal stenosis. CONCLUSION: VMAT concurrent with chemotherapy, BT, and local HT had a favorable short-term efficacy and acceptable toxicity on cervical cancer, which was an alternative option for LACC.

Safety and efficacy of CT-guided radioactive iodine-125 seed implantation as a salvage treatment for recurrent head and neck cancer after two or more courses of radiotherapy.

BACKGROUND: In the past, patients with recurrent head and neck cancer (rHNC) who had previously received a high dose of radiation and were unable to undergo surgery were mainly treated with palliative chemotherapy due to the high incidence of side effects from re-irradiation. With the development of radiotherapy technology, re-irradiation of recurrent lesions by radioactive iodine-125 seed implantation (RISI) has been proposed as a feasible therapeutic approach. This study aimed to investigate the safety and efficacy of computed tomography (CT)-guided RISI in the treatment of rHNC after two or more courses of radiotherapy, and to analyze the prognostic factors. METHODS: Data of 33 patients with rHNC who received CT-guided RISI after two or more courses of radiotherapy were collected and statistically analyzed. The median cumulative dose of the previous radiotherapy was 110 Gy. Short-term efficacy was assessed by Response Evaluation Criteria in Solid Tumors (version 1.1) criteria, while adverse events were evaluated by Common Terminology Criteria for Adverse Events (version 5.0) criteria. RESULTS: The median gross tumor volume (GTV) was 29.5 cc, and the postoperative median dose to 90% of target volume (D90) was 136.8 Gy. For adverse reactions, enhanced pain was found in 3 (9.1%) patients, followed by grade 1 to 2 acute skin reactions in 3 (9.1%) patients, grade 2 to 3 late skin reactions in 2 (6.1%) patients, grade 1 to 2 early mucosal reactions in 4 (12.1%) patients, and mandibular osteonecrosis in 1 (3.0%) patient. Regarding the treatment efficacy, the 1- and 2-year local control (LC) rates were 47.8% and 36.4% (median LC time, 10 months), and the 1- and 2-year overall survival (OS) rates were 41.3% and 32.2% (median OS time, 8 months). The absence of adverse events was associated with better LC. CONCLUSIONS: CT-guided RISI, as a salvage therapy, demonstrated acceptable safety and efficacy in the treatment of rHNC after two or more courses of radiotherapy. TRIAL REGISTRATION: This study was registered at Chinese Clinical Trial Register database (Registration No. ChiCTR2200063261 ) in September 2, 2022.

Tumor-derived semaphorin 3D promoting cancer cachexia via regulating hypothalamic pro-opiomelanocortin neurons.

Cachexia is very common in cancer patients and predicts a poor prognosis; however, the molecular basis for progress in these individuals remains unclear, especially the effect of tumors on the hypothalamus energy regulation center. To investigate the regulatory pathway of tumors associated with hypothalamic pro-opiomelanocortin (POMC) neurons known as appetite-inhibiting neurons, we conducted observations both on patients and mice models. Results showed that the highly expressed exocrine semaphorin 3D (SEMA3D) both in cachexia patients and mice was positively related to the expression of POMC and its proteolytic peptide. Compared with the control group, mice inoculated with the SEMA3D-knockout C26 cell line decreased the activity of POMC neurons resulting in a 1.3-fold increase in food intake, a 22.2% increase in body weight, and reduced skeletal muscle and fat catabolism. The effect of SEMA3D on cachexia progression can be partially alleviated by knocking-down POMC expression in the brain. In terms of mechanism, SEMA3D enhances the activity of POMC neurons by activating the expression of NRP2 (membrane receptor) and PlxnD1 (intracellular receptor). Our research revealed the overexpression of SEMA3D in tumors works as an activator of POMC neurons, which may play a vital role in suppressing appetite and promoting catabolic metabolism.

Targeting critical pathways in ferroptosis and enhancing antitumor therapy of Platinum drugs for colorectal cancer.

Colorectal cancer (CRC) can be resistant to platinum drugs, possibly through ferroptosis suppression, albeit the need for further work to completely understand this mechanism. This work aimed to sum up current findings pertaining to oxaliplatin resistance (OR) or resistance to ascertain the potential of ferroptosis to regulate oxaliplatin effects. In this review, tumor development relating to iron homeostasis, which includes levels of iron that ascertain cells' sensitivity to ferroptosis, oxidative stress, or lipid peroxidation in colorectal tumor cells that are connected with ferroptosis initiation, especially the role of c-Myc/NRF2 signaling in regulating iron homeostasis, coupled with NRF2/GPX4-mediated ferroptosis are discussed. Importantly, ferroptosis plays a key role in OR and ferroptotic induction may substantially reverse OR in CRC cells, which in turn could inhibit the imbalance of intracellular redox induced by oxaliplatin and ferroptosis, as well as cause chemotherapeutic resistance in CRC. Furthermore, fundamental research of small molecules, ferroptosis inducers, GPX4 inhibitors, or natural products for OR coupled with their clinical applications in CRC have also been summarized. Also, potential molecular targets and mechanisms of small molecules or drugs are discussed as well. Suggestively, OR of CRC cells could significantly be reversed by ferroptosis induction, wherein this result is discussed in the current review. Prospectively, the existing literature discussed in this review will provide a solid foundation for scientists to research the potential use of combined anticancer drugs which can overcome OR via targeting various mechanisms of ferroptosis. Especially, promising therapeutic strategies, challenges ,and opportunities for CRC therapy will be discussed.

Intakes of omega-3 fatty acids and risks of all-cause and cause-specific mortality in people with diabetes: a cohort study based on NHANES 1999-2014.

AIMS: Intake of omega-3 fatty acids is associated with several health benefits, but the specific benefits in populations with diabetes have yet to be elucidated. Therefore, this study aimed to explore the relationship between intake of omega-3 fatty acids and mortality in people with diabetes. METHODS: This was a prospective cohort study and included 4854 participants with diabetes (mean age, 57.92 years; 50.9% male) from the National Health and Nutrition Examination Survey (1999-2014). Eicosapentaenoic (EPA) and docosahexaenoic (DHA) acid intake were used as alternative markers of omega-3 fatty acids intake and calculated based on the sum of the 24-h dietary recall interviews and dietary supplements. Mortality data were ascertained by linkage to National Death Index records by December 31, 2015. Cox proportional hazard models and restricted cubic spline were used to assess the relationship between EPA and DHA intake and all-cause and cause-specific mortality. Statistical analyses were performed using R 4.2.0 software. RESULTS: Compared with participants with a lower EPA + DHA intake, participants who had a higher EPA + DHA intake tended to be Non-Hispanic Black; were more likely to be obese; and had higher daily energy intake and family income. During 34,386 person-years of follow-up, 1102 deaths were documented, including 266 cardiovascular disease deaths and 152 cancer deaths. In multivariable regression analyses with adjustment of confounding factors, higher EPA + DHA intake was significantly and linearly related to lower all-cause mortality: there was a 25% reduced risk of all-cause mortality. CONCLUSIONS: Higher omega-3 fatty acid intake was independently related to lower all-cause mortality in individuals with diabetes, suggesting an adequate intake of omega-3 fatty acids may prevent premature death among the population with diabetes.

Glutamine Transporter SLC1A5 Regulates Ionizing Radiation-Derived Oxidative Damage and Ferroptosis.

Ionizing radiation-derived oxidative stress and ferroptosis are one of the most important biological effects on destroying the liver tumor, whereas radioresistance of liver tumor remains a leading cause of radiotherapy (RT) failure mainly because of the protective antiferroptosis, in which oxidative stress and subsequent lipid peroxidation are the key initiators. Thus, it is of great importance to overcome ferroptosis resistance to improve the therapeutic efficacy of RT in liver tumor patients. Irradiation-resistant HepG2 cells (HepG2-IRR) were established by long-term exposure to X-ray (2 to 8 Gy), and targeted metabolomics analysis revealed an obvious increase in intracellular amino acids in HepG2-IRR cells upon ferroptosis stress. Among these amino acids with obvious changes, N-acetylglutamine, a derivative of glutamine, is essential for the redox homeostasis and progression of tumor cells. Interestingly, the treatment of glutamine starvation could promote the ferroptosis effect significantly, whereas glutamine supplementation reversed the ferroptosis effect completely. Consistent with the changes in amino acids pattern, the glutamine transporter SLC1A5 was verified in liver tumor samples from TCGA training and validation cohorts as an independent prognostic amino acid-ferroptosis gene (AFG). A risk score for screening prognosis based on the SLC1A5, SLC7A11, ASNS, and TXNRD1 demonstrated that a high-risk score was correlated with poor survival. In vitro studies had shown that the knockdown of SLC1A5 resulted in a significant decrease in cell viability and promoted lipid peroxidation and oxidative damage introduced by irradiation (10 Gy). Collectively, our findings indicated that SLC1A5 may act as a suppressor gene against ferroptosis and can be a potential target for ionizing radiation mediated effects.

Clinical practice guidelines on image-guided thermal ablation of primary and metastatic lung tumors (2022 edition).

The main contents of the Clinical Practice Guidelines on Image-Guided Thermal Ablation (IGTA) of Primary and Metastatic Lung Tumors (2022 Edition) include the following: epidemiology of primary and metastatic lung tumors; the concepts of the IGTA and common technical features; procedures, indications, contraindications, outcomes evaluation, and related complications of IGTA on primary and metastatic lung tumors; and limitations and future development.

Combined fractional anisotropy and subcortical volumetric deficits in patients with mild-to-moderate depression: Evidence from the treatment of antidepressant traditional Chinese medicine.

Numerous neuroimaging studies have demonstrated that diverse brain structural plasticity could occur in a human brain during a depressive episode. However, there is a lack of knowledge regarding the underlying mechanisms of mild-to-moderate depression (MMD), especially the changes of brain structural characteristics after treatment with the Shuganjieyu capsule (SG), a kind of traditional Chinese medicine that has been recommended for the specialized treatment of MMD. In this study, we investigated the structural brain plasticity in MMD that have been undergoing 8 weeks of SG treatment compared with age- and sex-matched healthy controls (HCs) and assessed the relationship between these brain structural alternations and clinical symptoms in MMD. At the baseline, we found that: (1) fractional anisotropy (FA) values in patients with MMD were found to be significantly increased in the regions of anterior limb of internal capsule (ALIC) [MNI coordinates: Peak (x/y/z) = 102, 126, 77; MMD FA peak (Mean ± SD) = 0.621 ± 0.043; HCs FA peak (Mean ± SD) = 0.524 ± 0.052; MMD > HCs, t = 9.625, p < 0.001] and posterior limb of internal capsule (PLIC) [MNI coordinates: Peak (x/y/z) = 109, 117, 87; MMD FA peak (Mean ± SD) = 0.694 ± 0.042; HCs FA peak (Mean ± SD) = 0.581 ± 0.041; MMD > HCs, t = 12.90, p < 0.001], and FA values were significantly positively correlated with HAMD scores in patients with MMD. (2) Patients with MMD showed smaller gray matter volume (GMV) of the dorsolateral prefrontal cortex (DLPFC), frontal cortex, occipital cortex, and precuneus, and the GMV of DLPFC was negatively correlated with HAMD scores. After SG treatment, we found that (1) the HAMD scores decreased; (2) FA values were significantly decreased in the regions of the ALIC and PLIC compared to those at baseline and TBSS revealed no significant differences in FA values between patients with MMD and HCs. (3) The structural characteristics of DLPFC in patients with MMD obtained at the 8th week were improved, e.g., no significant differences in GMV of DLPFC between the two groups. Taken together, our results provided neuroimaging evidence suggesting that SG is an effective treatment for patients with MMD. Moreover, alterations of GMV after 8 weeks of SG treatment indicated a potential modulation mechanism in brain structural plasticity within the DLPFC in patients with MMD.

BSA-templated ultrasmall Ag/Gd2O3 as a self-enabled nanotheranostic for MR/CT/PA tri-modality imaging and photothermal therapy.

It is becoming more and more important to effectively integrate multiple complementary diagnostic imaging and synergistic therapies into a nano-platform, but it is still challenging. Here, we used bovine serum albumin (BSA) as a template to prepare ultra-small Ag/Gd2O3 (Ag/Gd@BSA) hybrid nanoparticles with high water dispersion by a biomineralization strategy for magnetic resonance (MR)/computed tomography (CT)/photoacoustic (PA) imaging-guided photothermal therapy (PTT). Compared with commercial MR and CT contrast agents, we showed that these well-characterized BSA-templated nanotheranostics possessed higher r1 relaxivity (5.84 mM-1 s-1) and HU values. In addition, these nanotheranostics have an excellent NIR absorption feature and outstanding photothermal conversion efficiency (47.4%) in the solution phase. The in vivo imaging experiment demonstrated that the Ag/Gd@BSA hybrid nanoparticles could serve as tri-modality imaging contrast agents to enable precise diagnosis of tumors. Meanwhile, it was also revealed that Ag/Gd@BSA had ability to be an ideal nanotherapeutic agent to achieve a satisfactory tumor treatment effect through PTT. Also, we showed the good biocompatibility of Ag/Gd@BSA nanoparticles. Overall, these results indicated that Ag/Gd@BSA was an effective nanotheranostic, which could accurately identify tumor sites and realize complete tumor elimination, having great potential in clinical transformation.

The powerful brain: Neural correlates of sense of power and hope.

A sense of power refers to the perception that one can control and influence others' states by providing or withholding valued resources in an asymmetrical way, and which has been associated with greater hope. However, little is known about the neural bases underlying this association. The present study aimed to examine these phenomena in 261 healthy adolescent students by assessing resting-state brain activity (i.e., the amplitude of low-frequency fluctuations, ALFF) and connectivity (i.e., resting-state functional connectivity, RSFC). Whole-brain correlation analyses revealed that higher levels of perceived power were linked with reduced ALFF in the left thalamus and increased RSFC between the left thalamus and left superior temporal gyrus. Mediation analyses further showed that perceived power mediated the influence of the left thalamus activity on hope. Our results remained significant even after controlling for the head motion, age, and gender. Our findings contribute to the neurobiological basis of a sense of power and the neural mechanism underlying the relationship between a sense of power and hope.

Mutation of glucose-methanol-choline oxidoreductase leads to thermosensitive genic male sterility in rice and Arabidopsis.

Thermosensitive genic male sterility (TGMS) lines serve as the major genetic resource for two-line hybrid breeding in rice. However, their unstable sterility under occasional low temperatures in summer highly limits their application. In this study, we identified a novel rice TGMS line, ostms18, of cultivar ZH11 (Oryza sativa ssp. japonica). ostms18 sterility is more stable in summer than the TGMS line carrying the widely used locus tms5 in the ZH11 genetic background, suggesting its potential application for rice breeding. The ostms18 TGMS trait is caused by the point mutation from Gly to Ser in a glucose-methanol-choline (GMC) oxidoreductase; knockout of the oxidoreductase was previously reported to cause complete male sterility. Cellular analysis revealed the pollen wall of ostms18 to be defective, leading to aborted pollen under high temperature. Further analysis showed that the tapetal transcription factor OsMS188 directly regulates OsTMS18 for pollen wall formation. Under low temperature, the flawed pollen wall in ostms18 is sufficient to protect its microspore, allowing for development of functional pollen and restoring fertility. We identified the orthologous gene in Arabidopsis. Although mutants for the gene were fertile under normal conditions (24°C), fertility was significantly reduced under high temperature (28°C), exhibiting a TGMS trait. A cellular mechanism integrated with genetic mutations and different plant species for fertility restoration of TGMS lines is proposed.

Neuroanatomical Correlates of Mild-to-Moderate Depression: Memory Ability Mediates the Association Between Gray Matter Volume and Antidepressant Treatment Outcome.

Mild-to-moderate depression (MMD) is frequently encountered in clinical practice. Investigating the brain mechanism and its relationship with symptoms in patients with MMD can help us understand the occurrence and development of depression, thus optimizing the prevention and treatment of depression. Shugan Jieyu capsule (SG), a traditional Chinese medicine, is commonly used to ameliorate emotional and cognitive symptoms induced by patients with MMD. Combining clinical assessments and magnetic resonance imaging (MRI), we obtained the emotional and cognitive status of MMD patients and also explored the structural and functional alterations in MMD patients after SG treatments. Structural MRI demonstrated that the gray matter volumes of the left thalamus, right thalamus, and right amygdala in MMD patients were significantly smaller than in healthy controls, and the right amygdala volume was negatively related to depression symptoms in MMD patients. Resting-state functional MRI data demonstrated that MMD patients exhibited decreased temporal coupling between the right amygdala and nucleus accumbens, which was further associated with the severity of depression. Furthermore, right amygdala volume at baseline served as a significant predictor to identify the treatment outcome after 8 weeks of SG treatment in the patients' group, and importantly, the memory ability mediated the relationship from right amygdala volume to the treatment outcome. These data revealed the structural and functional deficits in the right amygdala, which were highly correlated with the symptoms of depression and its cognitive ability, likely predicting treatment outcome. Therefore, this study strengthened our understanding of the pathogenesis of MMD, which is hoped that it will contribute to tailoring a personalized method for treating the patients.

A mediating model of mindfulness, sense of purpose in life and mental health among Chinese graduate students.

The purpose of the present study is to examine the relationship between mindfulness and mental health of graduate students and the mediating effects of sense of purpose in life on mindfulness and mental health. The participants include 419 graduate students from 6 universities in China, and there are 190 males and 229 females. The Hayes Process is adopted to analyze the effects of the sense of purpose in life on mindfulness and mental health of graduate students. The results reveal that mindfulness can effect the mental health of graduate students positively and significantly. The sense of purpose in life is found to mediate the relationship between mindfulness and mental health. In further moderated mediation analyses, the effect of mindfulness on mental health can be adjusted by family economic condition. The type of degree can adjust the effect of mindfulness on sense of purpose, and academic Interest can adjust the mediating effect of sense of purpose. Finally, this study discusses several empirical and methodological implications of the findings.

Deep regional hyperthermia combined with modern concurrent chemoradiotherapy increases T-downstaging rate in locally advanced rectal cancer.

BACKGROUND: Deep regional hyperthermia might have an additional effect on radiotherapy in treating locally advanced rectal cancer (LARC). This study aimed to investigate the role of hyperthermia combined with modern preoperative concurrent chemoradiotherapy (CRT) for LARC. METHODS AND MATERIALS: From 2012 to 2018, 152 consecutive patients with LARC treated with neoadjuvant chemoradiation were enrolled and analyzed retrospectively. Pelvic radiotherapy (45-50 Gy) was delivered as volumetric modulated arc therapy (VMAT), concurrently with capecitabine chemotherapy. Fifty patients received hyperthermia combined with CRT (HCRT group) twice a week. Treatment response and outcomes were compared between the two groups. Furthermore, the relationships between peripheral blood neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) in response to hyperthermia were analyzed. RESULTS: Patients treated with hyperthermia had a significantly higher T-downstaging rate than those without hyperthermia (82.0 vs. 62.7%; p = .016). Hyperthermia was an independent favorable predictor of T-downstaging (odds ratio [OR] = 2.473; 95% confidence interval [CI] 1.050-5.826; p = .038). In the HCRT group, a pre-therapeutic elevated NLR (≥3) was associated with a higher T-downstaging rate (100.0 vs. 73.5%, p = .043). However, NLR was not associated with the T-downstaging rate in the CRT group. Five-year rates of locoregional recurrence-free survival (96.8 vs. 94.7%, p = .959), disease-free survival (DFS; 61.4 vs. 79.3%, p = .242), and overall survival (OS; 92.7 vs. 89.8%, p = .831) were not statistically different between the CRT and HCRT groups. CONCLUSIONS: Hyperthermia can improve preoperative treatment response in LARC. Pretreatment NLR may be a predictive factor for hyperthermia.

PD-1 Inhibitor Maintenance Therapy Combined Iodine-125 Seed Implantation Successfully Salvage Recurrent Cervical Cancer after CCRT: A Case Report.

Cervical cancer is the fourth most common cancer in females worldwide. Patients with stage III and IV cervical cancer based on the Federation of Gynecology and Obstetrics (FIGO) classification have higher recurrence rates. Because of organs at risk (OAR) protection and the low indication rate of salvage surgery, the choice of treatment is always challenging. Systemic chemotherapy is palliative and can be performed in conjunction with surgery or radiotherapy; however, it has no significant benefit to survival. Brachytherapy and stereotactic body radiotherapy (SBRT) are characterized by extremely high radiation doses applied to tumor cells while sparing the normal tissues. Several studies have investigated the efficacy of these technologies in recurrent cervical cancer and showed promising results. The immune checkpoint inhibitors approach was also investigated and showed promising results too. Herein, we report a case of a patient with cervical cancer that recurred five months after adjuvant chemotherapy and concurrent chemoradiotherapy. The disease prognosis after interstitial implantation brachytherapy (IIB) was determined. Then, the patient underwent radioactive 125I-seed implantation combined with PD-1 inhibitor treatment. The patient exhibited a partial response after seed implantation, and up to now, the duration of this partial response was 24 months.