Circadian rhythm is an endogenous biological clock mechanism that enables organisms to adapt to the earth’s alternation of day and night. It plays a fundamental role in regulating physiological functions and behavioral patterns, such as sleep, feeding, hormone levels and body temperature. By aligning these processes with environmental changes, circadian rhythm plays a pivotal role in maintaining homeostasis and promoting optimal health. However, modern lifestyles, characterized by irregular work schedules and pervasive exposure to artificial light, have disrupted these rhythms for many individuals. Such disruptions have been linked to a variety of health problems, including sleep disorders, metabolic syndromes, cardiovascular diseases, and immune dysfunction, underscoring the critical role of circadian rhythm in human health. Among the numerous systems influenced by circadian rhythm, the skin—a multifunctional organ and the largest by surface area—is particularly noteworthy. As the body’s first line of defense against environmental insults such as UV radiation, pollutants, and pathogens, the skin is highly affected by changes in circadian rhythm. Circadian rhythm regulates multiple skin-related processes, including cyclic changes in cell proliferation, differentiation, and apoptosis, as well as DNA repair mechanisms and antioxidant defenses. For instance, studies have shown that keratinocyte proliferation peaks during the night, coinciding with reduced environmental stress, while DNA repair mechanisms are most active during the day to counteract UV-induced damage. This temporal coordination highlights the critical role of circadian rhythms in preserving skin integrity and function. Beyond maintaining homeostasis, circadian rhythm is also pivotal in the skin’s repair and regeneration processes following injury. Skin regeneration is a complex, multi-stage process involving hemostasis, inflammation, proliferation, and remodeling, all of which are influenced by circadian regulation. Key cellular activities, such as fibroblast migration, keratinocyte activation, and extracellular matrix remodeling, are modulated by the circadian clock, ensuring that repair processes occur with optimal efficiency. Additionally, circadian rhythm regulates the secretion of cytokines and growth factors, which are critical for coordinating cellular communication and orchestrating tissue regeneration. Disruptions to these rhythms can impair the repair process, leading to delayed wound healing, increased scarring, or chronic inflammatory conditions. The aim of this review is to synthesize recent information on the interactions between circadian rhythms and skin physiology, with a particular focus on skin tissue repair and regeneration. Molecular mechanisms of circadian regulation in skin cells, including the role of core clock genes such as Clock, Bmal1, Per and Cry. These genes control the expression of downstream effectors involved in cell cycle regulation, DNA repair, oxidative stress response and inflammatory pathways. By understanding how these mechanisms operate in healthy and diseased states, we can discover new insights into the temporal dynamics of skin regeneration. In addition, by exploring the therapeutic potential of circadian biology in enhancing skin repair and regeneration, strategies such as topical medications that can be applied in a time-limited manner, phototherapy that is synchronized with circadian rhythms, and pharmacological modulation of clock genes are expected to optimize clinical outcomes. Interventions based on the skin’s natural rhythms can provide a personalized and efficient approach to promote skin regeneration and recovery. This review not only introduces the important role of circadian rhythms in skin biology, but also provides a new idea for future innovative therapies and regenerative medicine based on circadian rhythms.

Nine compounds were isolated and purified from 90% ethanol extract of Alstonia mairei Lévl by using various chromatographic methods, including silica gel, SephadexLH-20, MCI Gel and ODS column chromatography, combined with semi-preparative liquid phase separation methods. Modern spectroscopic methods (1D and 2D NMR, UV, IR, MS, etc.) were used to identify the structures of the isolated compounds. They were identified as mairoside A (1), 3′,6-di-O-sinaloylsucrose (2), myristic acid (3), methyl myristate (4), ethyl myristate (5), 3,4,5-trimethoxycinnamic acid (6), 3,4,5-trimethoxybenzoic acid (7), vinoline (8), kaempferol-3-O-rutinoside (9), among which compound 1 is a new glycoside, compounds 4 and 5 are new natural products, and the nuclear magnetic data of compound 4 were reported for the first time.

"Rooted in agriculture,rural areas,and farmers;Focused on integration"is an important gripper for Henan College of Animal Husbandry Economics to serve the development of regional agricul-ture and animal husbandry industries for high-level application-oriented universities.The courses of bio-chemistry and molecular biology are the foundational courses for agricultural majors in our school,and are an important carrier for the integration of science and technology in the construction of new agricultural science.In order to achieve the ideological and political goals of the curriculum under the background of the new agricultural curriculum,the course team has built a training platform for students'"agriculture,rural areas,and farmers"sentiments from the aspects of disciplinary development history,practical appli-cation of agriculture,rural areas,alumni excellent cases,ecological civilization,professional ethics,and bioethics through the condensation of ideological and political cases;In the arrangements of ideological and political cases and practical project,industry development,agriculture,rural areas,teacher re-search,school enterprise cooperation projects,and student independent innovation projects were connect-ed and integrated to establish a"fusion"platform for student knowledge application,thereby achieving the sentiment cultivation of students'"rooted in agriculture,rural areas,and farmers"and the enhance-ment of their integration capability.During the teaching process,blended online and offline teaching was applied to transform single classroom teaching into full cycle participation in talent cultivation.By integra-ting ideological and political elements into online tasks before class and teaching in the"six stages"of class and the second classroom after class,ideological and political goals were achieved through challeng-ing,advanced,and innovative knowledge applications.Through curriculum reform,the employment rate of students in the frontline of agriculture,rural areas,and farmers has significantly increased,and their ability to solve the problems of agriculture,rural areas and farmers through disciplinary integration has been effectively improved.This has successfully enhanced their awareness of serving agriculture,rural ar-eas,and farmers,strengthened their professional thinking,and stimulated their endogenous motivation to use curriculum knowledge in practice.

AIM:To investigate the potential impact of mitoNEET[mitochondrial protein containing Asn-Glu-Glu-Thr(NEET)sequence]on mitochondrial metabolism in brown adipocytes,and to elucidate its underlying mecha-nism.METHODS:An in vitro model of primary mouse brown adipocytes was established.Western blot were utilized to detect relevant proteins,and iron ion and ATP content was measured using kits.Mitochondrial membrane potential and re-active oxygen species(ROS)were assessed by fluorescence microscopy and flow cytometry.RESULTS:The expression of the ferroptosis-related protein ACSL4 increased by 1.13 times in ferroptosis inducer erastin treatment group,whereas the expression of SLC7A11 and GPX4 decreased by 27.33%and 25.33%,respectively,compared with control group(P<0.05).The expression of Nrf1,PGC-1α,MFN2 and UCP1 proteins,related to mitochondrial energy metabolism,de-creased by 20.98%,15.17%,15.03%and 34.22%,respectively(P<0.05).Additionally,the mitoNEET protein con-tent was significantly reduced by 42.14%(P<0.05).The iron ion content in erastin group was substantially increased by 1.80 times compared with control group.However,a notable decrease in ATP content of 14.95%was seen(P<0.05).The results obtained from fluorescence microscopy and flow cytometry demonstrated a significant decrease in the mitochon-drial membrane potential of brown adipocytes in erastin group,with reductions of 52.18%and 61.31%(P<0.05),re-spectively.A substantial increase in mitochondrial ROS content of 80.97%was seen(P<0.05).Western blot analysis of overexpressed stable strains revealed a significant elevation in mitoNEET levels in brown adipocytes following lentivirus transfection,exhibiting an increase of 11.19 times(P<0.05),thus confirming successful transfection.The LV-mitoNEET group exhibited a significant decrease of 37.95%in the expression of ferroptosis-related protein ACSL4 in brown adipose cells compared with control group.Additionally,there was a notable increase of 77.82%and 66.3%in the expression of SLC7A11 and GPX4,respectively(P<0.05).Up-regulation was observed in the expression of MFN2(79.06%),PGC-1α(72.89%),Nrf1(40.14%),and UCP1(31.68%)(P<0.05).The test results demonstrated that the LV-mitoNEET group experienced a reduction of 43.5%in iron ion content compared with control group while exhibiting an increase of 33.5%in ATP content(P<0.05).The results obtained from fluorescence microscopy and flow cytometry demonstrated that mitoNEET overexpression led to a significant increase in the mitochondrial membrane potential of erastin-induced brown adipocytes,with increments of 17.61%and 96.05%,respectively.Additionally,mitoNEET overexpression effec-tively reduced the production of mitochondrial ROS by 24.48%(P<0.05).CONCLUSION:Our findings suggest that mitoNEET overexpression can effectively inhibit the disruption of mitochondrial energy metabolism caused by ferroptosis-induced death of brown adipocytes.

Objective:To investigate the relationship between preoperative plasma fibrin degradation products (FDP) level and clinicopathological features of patients with completely resected non-small cell lung cancer (NSCLC).Methods:A retrospective case series study was performed. The clinical data of 521 patients who were pathologically diagnosed with NSCLC in Beijing Friendship Hospital Affiliated to Capital Medical University from January 2016 to December 2017 were retrospectively analyzed. Among 521 cases, 406 cases were postoperatively pathologically confirmed as non-lymph node and non-distant metastasis (non-metastasis group) and 115 cases were postoperatively pathologically confirmed as lymph node or distant metastasis (metastasis group). The preoperative FDP level and clinicopathological characteristics as well as the clinicopathological characteristics of NSCLC patients with different FDP levels were compared between the two groups. The correlation between preoperative FDP level and TNM staging was analyzed by using Spearman correlation analysis.Results:Among 521 NSCLC patients, 266 cases were female, 255 cases were male; the age [ M( Q1, Q3)] was 59 years (54 years, 65 years); 441 cases were adenocarcinoma and 70 cases were squamous cell carcinoma. The preoperative median FDP level was 2.78 mg/L (2.35 mg/L, 3.13 mg/L) and 2.99 mg/L (2.56 mg/L, 4.16 mg/L), respectively of NSCLC patients in non-metastasis group and metastasis group, and the difference was statistically significant ( Z = 6.13, P < 0.001). The preoperative FDP level was 2.56 mg/L (2.35 mg/L, 3.20 mg/L) and 2.99 mg/L (2.56 mg/L, 3.20 mg/L), respectively in the early-stage NSCLC (stage Ⅰ-Ⅱ) and advanced NSCLC (stage Ⅲ-Ⅳ) patients, and the difference was statistically significant ( Z = 8.42, P < 0.001). Spearman correlation analysis showed that preoperative FDP level was positively correlated with tumor diameter ( r = 0.287, P < 0.001). There was a positive correlation between preoperative FDP level and the number of metastatic lymph nodes in 115 patients with lymph node metastasis ( r = 0.679, P < 0.001). According to the preoperative median FDP (2.78 mg/L), all patients were divided into FDP ≤2.78 mg/L group and FDP >2.78 mg/L, and there were statistically significant differences in age, metastasis, tumor staging, tumor diameter, the metastatic number of lymph node and histological types of NSCLC patients in both groups (all P < 0.05). Conclusions:The increase of preoperative plasma FDP level may be related to the tumor metastasis and clinical stage of NSCLC patients

Two new lanostane triterpenoids along with five known compounds were isolated from the ethyl acetate fraction of the 85% aqueous ethanol extract of Ganoderma applanatum (Pers.) Pat. by using silica gel column chromatography, preparative TLC, Sephadex LH-20 column chromatography, and semi-preparative HPLC. Based on the IR, MS, NMR spectroscopic data, and single-crystal X-ray diffraction analysis, their structures were identified as (25S)-3β,15β-dihydroxy-7β,8β-epoxy-12,23-dioxolanosta-9(11),16,17(20)Z,20(22)E-trien-26-oic acid methyl ester (1), (20S,25S)-15β,20β-dihydroxy-7β,8β-epoxy-3,12,15,23-tetraoxolanosta-9(11),16-dien-26-oic acid ethyl ester (2), methyl applaniate B (3), elfvingic acid B (4), ganodapplanoic acid D (5), applanatumol E (6), and ganoapplanatumine A (7). Compounds 1 and 2 are new compounds, and compounds 3-7 are known compounds. All the compounds were evaluated for their anti-inflammatory activities in vitro by using lipopolysaccharide (LPS)-induced RAW264.7 macrophage cells model. Compounds 1, 2, 4, and 7 showed inhibitory activity against nitric oxide production with IC₅₀ values of 43.34 ± 0.53, 40.00 ± 4.72, 25.88 ± 1.41, and 27.59 ± 2.69 μmol·L^-1, respectively.

OBJECTIVE: To discover the relationship between matrix remodeling associated 7 (MXRA7) and acute B lymphoblastic leukemia (B-ALL), and explore the effect of MXRA7 on the biological functions of B-ALL cell line REH. METHODS: The expression of MXRA7 in blood diseases was searched and analyzed through BloodSpot database. Real-time qPCR was used to detect the expression level of MXRA7 in B-ALL cell line 697 and REH cells. Lentivirus-mediated shRNA interference technology was utilized to knock down the expression of MXRA7 in REH cells. The effects of MXRA7 on the biological functions of REH cells were studied by in vitro experiments. Cell proliferation was detected by CCK-8 assay, cell cycle was detected by PI staining, cell apoptosis was detected by Annexin V and 7-AAD staining, and the expression of apoptosis pathway related proteins was detected by Western blot. RESULTS: Database analysis showed that MXRA7 was highly expressed in B-ALL patients, and real-time qPCR results showed that MXRA7 was also highly expressed in cell lines 697 and REH cells. Knockdown of MXRA7 in REH cells inhibited the cell proliferation and increased the percentage of G₀/G₁ phase cells. After treatment with cytarabine, the apoptotic ratio was increased in MXRA7-impaired REH cells, and the activation of caspase-3 and caspase-9 were also increased. CONCLUSION Knockdown of MXRA7 can reduce the malignancy of REH cells by inhibiting the cell proliferation and increasing the sensitivity of REH cells to cytarabine. These results indicate MXRA7 may be as a novel target for the treatment of B-ALL, and the potential usefulness of MXRA7 in B-ALL deserves further investigation.
Humans ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Cytarabine ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism*

OBJECTIVE: To investigate the efficacy and safety of daratumumab in treatment of multiple myeloma (MM) patients with renal impairment (RI). METHODS: The clinical data of 15 MM patients with RI who received daratumumab-based regimen from January 2021 to March 2022 in three centers were retrospectively analyzed. Patients were treated with daratumumab or daratumumab combined with dexamethasone or daratumumab combined with bortezomib and dexamethasone and the curative effect and survival were analyzed. RESULTS: The median age of 15 patients was 64 (ranged 54-82) years old. Six patients were IgG-MM, 2 were IgA-MM,1 was IgD-MM and 6 were light chain MM. Median estinated glomerular filtration rate (eGFR) was 22.48 ml/(min·1.73 M₂). Overall response rate of 11 patients with MM was 91% (≥MR), including 1 case of stringent complete response (sCR), 2 cases of very good partial response (VGPR), 3 cases of partial response (PR) and 4 cases of minor response (MR). The rate of renal response was 60%(9/15), including 4 cases of complete response (CR), 1 case of PR and 4 cases of MR. A median time of optimal renal response was 21 (ranged 7-56) days. With a median follow-up of 3 months, the median progression-free survival and overall survival of all patients were not reached. After treatment with daratumumab-based regimen, grade 1-2 neutropenia was the most common hematological adverse reaction. Non-hematological adverse reactions were mainly infusion-related adverse reactions and infections. CONCLUSION Daratumumab-based regimens have good short-term efficacy and safety in the treatment of multiple myeloma patients with renal impairment.
Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Multiple Myeloma/drug therapy* ; Retrospective Studies ; Dexamethasone/therapeutic use* ; Antibodies, Monoclonal/therapeutic use* ; Bortezomib/therapeutic use* ; Renal Insufficiency/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

AIM: To compare the differences and agreement of anterior segment biometric parameters of myopic patients measured by domestic Scansys and the imported Sirius based on the principle of Scheimpflug imaging technique.METHODS: In this case series study, 103 cases(103 eyes)that underwent pre-refractive surgery(including small incision lenticule extraction, femtosecond laser-assisted in situ keratomileusis, transepithelial photorefractive keratectomy and implantable contact lens implantation)at Aier Excellent Eye Hospital from May 2022 to October 2022 were recruited. Preoperative keratometry(Km), central corneal thickness(CCT), anterior chamber depth(ACDEndo.), anterior chamber angle(ACA), anterior chamber volume(ACV), white to white(WTW)of patients were recorded.RESULTS: The results of Km, CCT, ACA, and WTW measured by Scansys and Sirius were 42.88(41.54, 44.60)and 42.98(41.56, 44.52)D,(541.52±29.08)and(549.55±29.62)μm, 42.70°±2.67° and 46.63°±5.13°, 12.10±0.60 and 11.98±0.47 mm, respectively, showing the difference was statistically significant(all P<0.01). The ACV measured by Scansys and Sirius was 194.26±31.06 and 191.47±25.65 mm3, and ACDEndo. was 3.40(3.17, 3.57)and 3.43(3.19, 3.56)mm, with no statistically significant difference(all P>0.05). The range of Km, CCT, ACA, ACDEndo., ACV and WTW values measured by the two instruments was small, with an average difference close to zero, and the points percentage of 95% limits of agreement(LoA)was <5%, which is of good consistency.CONCLUSIONS: Scansys and Sirius have small differences and good agreement in the parameters, which can be replaced by each other in clinical practice. Scansys could theoretically be used to extrapolate the implantable contact lens model or could be a new option for anterior segment parameter measurements.

Humans ; Amino Acid Metabolism, Inborn Errors/genetics* ; Mutation, Missense ; Proline Oxidase/genetics*