Fasting, a Potential Intervention in Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the onset of symptoms, typically occurring later in life, and significant deficits in cognitive functions including learning, memory, speech, and behavior. Ongoing research endeavors seek to explore methods for preventing and treating AD, as well as delving into the molecular mechanisms underlying existing and novel therapeutic approaches encompassing exercise, diet, and drug regimens for individuals with AD or those at risk of developing AD. Among these interventions, dietary interventions have garnered increasing attention due to their potential in addressing the disease. Eating is among the most fundamental of human daily activities, and controlled dietary practices, such as fasting, have gained prominence as essential clinical methods for disease prevention and treatment. Research findings indicate that fasting holds promise in effectively alleviating and improving the cognitive decline associated with age or as consequence of disease. The clinical efficacy of fasting in addressing AD and related disorders might be grounded in its influence on various molecular mechanisms, including neuroinflammation, glial cell activation, insulin resistance, autophagy regulation, nerve regeneration, the gut microbiome, and accumulations of amyloid-ß and tau proteins. The present study reviews possible molecular mechanisms underpinning the therapeutic effects of fasting in patients with AD, as well as in models of the disorder, to establish a theoretical basis for using fasting as a viable approach to treat AD.

Structural bases of inhibitory mechanism of CaV1.2 channel inhibitors.

The voltage-gated calcium channel CaV1.2 is essential for cardiac and vessel smooth muscle contractility and brain function. Accumulating evidence demonstrates that malfunctions of CaV1.2 are involved in brain and heart diseases. Pharmacological inhibition of CaV1.2 is therefore of therapeutic value. Here, we report cryo-EM structures of CaV1.2 in the absence or presence of the antirheumatic drug tetrandrine or antihypertensive drug benidipine. Tetrandrine acts as a pore blocker in a pocket composed of S6II, S6III, and S6IV helices and forms extensive hydrophobic interactions with CaV1.2. Our structure elucidates that benidipine is located in the DIII-DIV fenestration site. Its hydrophobic sidechain, phenylpiperidine, is positioned at the exterior of the pore domain and cradled within a hydrophobic pocket formed by S5DIII, S6DIII, and S6DIV helices, providing additional interactions to exert inhibitory effects on both L-type and T-type voltage gated calcium channels. These findings provide the structural foundation for the rational design and optimization of therapeutic inhibitors of voltage-gated calcium channels.

Efficacy of Dan'e Fukang Soft Extract in Moderate Ovarian Hyperstimulation Syndrome for Concurrent Treatment of Blood and Fluid Guided by the "Triple Prevention" Principle.

Objective: This study aimed to evaluate the therapeutic efficacy and safety of Dan'e Fukang soft extracts in moderate ovarian hyperstimulation syndrome (OHSS) for the simultaneous treatment of blood and fluid, guided by the traditional Chinese medicine principle of "triple prevention". Methods: This study conducted a retrospective analysis of clinical data from outpatients who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection embryo transfer (ICSI-ET). A total of 2245 cases were included and divided into a treatment group (1002 cases) and a control group (1243 cases). Patients in the treatment group were administered Dan'e Fukang soft extracts orally in addition to conventional Western medicine. Comparative assessments were made between the two groups on pelvic ascites volume, maximum ovary diameter, dysmenorrhea incidence post-oocyte retrieval, and safety indicators. Results: There were no statistically significant differences between the treatment group and the control group in terms of general characteristics or the levels of follicle-stimulating hormone (FSH), luteotropic hormone (LH), estradiol (E2), or progesterone (P) at the time of gonadotropin (Gn) initiation. The groups did not differ significantly when we compared the levels of LH, E2, or P on the day of human chorionic gonadotropin (hCG) injection and during ovarian hyperstimulation protocols (P > 0.05 for all indicators). The differences in the volume of pelvic ascites, the maximum ovarian diameter, and the incidence of dysmenorrhea after oocyte retrieval were statistically significant between the treatment group and the control group (P < 0.05 in both). There were no instances of adverse reactions in either group. Conclusion: Based on the traditional Chinese medicine principle of "triple prevention", the use of Dan'e Fukang soft extracts for the simultaneous treatment of blood and fluid in moderate OHSS significantly improved the absorption of pelvic ascites, promoted ovarian recovery, and reduced the incidence of dysmenorrhea after oocyte retrieval.

Nonlinear optical properties in chiral copper oxide nanosheets.

Chiral transition metal oxides (TMOs) are in the forefront of research as potential active materials in various optoelectronic applications. However, the nonlinear optical (NLO) properties of the chiral TMOs have not been fully understood. Here, several kinds of copper oxide nanosheets capped with different chiral amino acids are synthesized. Notably, we investigate the NLO activities of these materials, including broadband second harmonic generation and transformation of nonlinear optical properties from saturable absorption to reverse saturable absorption. This work will broaden the use of chiral TMO materials in nonlinear photonic devices.

Rare Unilateral Twin Ectopic Pregnancy After Frozen Embryo Transfer: A Case Report and Literature Review.

Background: Unilateral twin ectopic pregnancy is extremely rare in natural pregnancy, with an incidence rate of only 1 in 200,000-2,500,000, represents a major health risk for reproductive-aged women, leading to even life-threatening complications. There is a lack of data on the prevalence of this rare disease after in-vitro fertilization-embryo transfer (IVF-ET) cycles. Case Report: We present a case of a 51-year-old woman with rare unilateral twin ectopic pregnancy after frozen embryo transfer treated with bilateral salpingectomy, followed by a review of the literature. Conclusion: Twin ectopic pregnancy is a very rare type of pregnancy that requires a high index of suspicion to diagnose and treat early to prevent complications and maternal death.

Effects of the Severe Acute Respiratory Syndrome Coronavirus 2 Inactivated Vaccine on the Outcome of Frozen Embryo Transfers: A Large Scale Clinical Study.

Background: Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a life-threatening infectious disease that has become a global pandemic. Objective: This study aimed to explore the effects of SARS-CoV-2 inactivated vaccine on the outcome of frozen embryo transfer (FET). Methods: We grouped patients who underwent FET between August 2021 and March 2022 based on their vaccination status, number of doses, and the interval between the last dose and the FET, and then compared the differences in pregnancy outcomes among the groups. Results: There were 1084 vaccinated patients and 1228 non-vaccinated ones. There were significant differences in the live birth rate between the vaccination and non-vaccination groups (16.61% vs 28.26%), among the one-dose, two-dose, and three-dose groups (22.28% vs 19.51% vs 7.27%), and among the groups with interval ≤ 1 month, 1-2 months, and ≥ 2 months (38.38% vs 27.27% vs 12.03%). There were significant differences in the persistent pregnancy rate between the vaccination and non-vaccination groups (22.88% vs 14.09%), among the one-dose, two-dose, and three-dose groups (14.51% vs 23.80% vs 38.18%), and among the groups with interval ≤ 1 month, 1-2 months, and ≥ 2 months (1.01% vs 8.44% vs 28.16%). There were significant differences in the neonatal weight between the vaccination and non-vaccination groups [3805.50 (3746.00-3863.50) vs 2970.00 (2500.00-3400.00)]. There were significant differences in the premature birth rate among the one-dose, two-dose, and three-dose groups (23.26% vs 34.59% vs 100.00%), and among the groups with interval ≤ 1 month, 1-2 months, and ≥ 2 months (15.79% vs 21.43% vs 37.00%). Conclusion: Pregnancy outcomes were not affected by taking the SARS-CoV-2 inactivated vaccine before FET, the number of doses, and the interval between doses. These findings provide evidence supporting the safety of administering the SARS-CoV-2 inactivated vaccine during pregnancy, which can be used as a guide for vaccinating patients undergoing ART.

Identification of residues critical for the extension of Munc18-1 domain 3a.

BACKGROUND: Neurotransmitter release depends on the fusion of synaptic vesicles with the presynaptic membrane and is mainly mediated by SNARE complex assembly. During the transition of Munc18-1/Syntaxin-1 to the SNARE complex, the opening of the Syntaxin-1 linker region catalyzed by Munc13-1 leads to the extension of the domain 3a hinge loop, which enables domain 3a to bind SNARE motifs in Synaptobrevin-2 and Syntaxin-1 and template the SNARE complex assembly. However, the exact mechanism of domain 3a extension remains elusive. RESULTS: Here, we characterized residues on the domain 3a hinge loop that are crucial for the extension of domain 3a by using biophysical and biochemical approaches and electrophysiological recordings. We showed that the mutation of residues T323/M324/R325 disrupted Munc13-1-mediated SNARE complex assembly and membrane fusion starting from Munc18-1/Syntaxin-1 in vitro and caused severe defects in the synaptic exocytosis of mouse cortex neurons in vivo. Moreover, the mutation had no effect on the binding of Synaptobrevin-2 to isolated Munc18-1 or the conformational change of the Syntaxin-1 linker region catalyzed by the Munc13-1 MUN domain. However, the extension of the domain 3a hinge loop in Munc18-1/Syntaxin-1 was completely disrupted by the mutation, leading to the failure of Synaptobrevin-2 binding to Munc18-1/Syntaxin-1. CONCLUSIONS: Together with previous results, our data further support the model that the template function of Munc18-1 in SNARE complex assembly requires the extension of domain 3a, and particular residues in the domain 3a hinge loop are crucial for the autoinhibitory release of domain 3a after the MUN domain opens the Syntaxin-1 linker region.

Overexpression of SERPINA3 suppresses tumor progression by modulating SPOP/NF­κB in lung cancer.

The pathogenesis mechanism of lung cancer is very complex, with high incidence and mortality. Serpin family A member 3 (SERPINA3) expression levels were reduced in the sera of patients with lung cancer and may be a candidate diagnostic and prognostic survival biomarker in lung cancer, as previously reported. However, the detailed biological functions of SERPINA3 in the pathogenesis of lung cancer remain unknown. In the present study, it was aimed to explore the effects of SERPINA3 on the occurrence of lung cancer. SERPINA3 expression was assessed using bioinformatics database analysis and experimental detection. Then, the biological effects of SERPINA3 were investigated in a cell culture system and a xenograft model of human lung cancer. The potential regulatory mechanism of SERPINA3 in lung cancer was explored by data­independent acquisition mass spectrometry (DIA­MS) detection and further validated by western blotting (WB). The results indicated that SERPINA3 expression levels were significantly downregulated in lung cancer tissues and cell lines. At the cellular level, it was revealed that overexpressed SERPINA3 inhibited cell growth, proliferation, migration and invasion and promoted the apoptosis of lung cancer cells. Moreover, overexpressed SERPINA3 enhanced the sensitivity of lung cancer cells to osimertinib. In vivo, a xenograft model of human lung cancer was established with BALB/c nude mice. After the injection of A549 cells, the tumor growth of the tumor­bearing mice in the SERPINA3­overexpressing group increased more slowly, and the tumor volume was smaller than that in the empty­vector group. Mechanistically, a total of 65 differentially expressed proteins were identified. It was found that the speckle­type POZ protein (SPOP) was significantly upregulated in SERPINA3­overexpressing H157 cells using DIA­MS detection and analysis. WB validation showed that SPOP expression increased, and NF­kappaB (NF­κB) p65 was inhibited in cell lines and tumor tissues of mice when SERPINA3 was overexpressed. The present findings suggest that SERPINA3 is involved in the development of lung cancer and has an antineoplastic role in lung cancer.

NINJ1 triggers extravillous trophoblast cell dysfunction through blocking the STAT3 signaling pathway.

BACKGROUND: Trophoblasts are the most important parts of the placenta in early pregnancy. Trophoblast cell dysfunction can induce embryo implantation insufficiency, thereby resulting in multiple diseases, including recurrent spontaneous abortion (RSA). A previous study indicates higher nerve injury-induced protein 1 (NINJ1) RNA levels in the villi tissues of RSA patients. OBJECTIVE: This study aimed to investigate the effect of NINJ1 on trophoblast behaviors and pregnancy loss. METHODS: Fresh villi tissues were obtained from with RSA patients and patients with artificial selective abortion for personal reasons, and NINJ1 expression in these tissues was detected. Extravillous trophoblast cell line HTR-8/SVneo was transfected with small-interfering RNA targeting NINJ1 or NINJ1 overexpression vector to perform loss-/gain-of-function experiments. Spontaneous abortion (SA) was induced by mating CBA/J females with DBA/2 males and the pregnant females were intraperitoneally injected with adenovirus vector carrying NINJ1 short hairpin RNA. RESULTS: NINJ1 mRNA and protein levels were higher in the villi tissues of RSA patients than those of artificial selective abortion patients. NINJ1 knockdown promoted trophoblast cell proliferation, migration and invasion but inhibited cell apoptosis. Moreover, conditioned medium from NINJ1-depleted trophoblasts promoted the angiogenesis of human umbilical vein endothelial cells. NINJ1 knockdown also promoted activation of the signal transducer and activator of transcription 3 (STAT3) signaling pathway in trophoblasts, and STAT3 inhibitor reversed NINJ1 knockdown-induced effects on trophoblast behaviors. Furthermore, pregnancy loss was attenuated by NINJ1 inhibition. CONCLUSION: NINJ1 contributes to the development of SA and triggers trophoblast cell dysfunction through inhibiting the STAT3 pathway.

Development of Y2O3 Dispersion-Strengthened Copper Alloy by Sol-Gel Method.

In this study, oxide dispersion-strengthened Cu alloy with a Y2O3 content of 1 wt.% was fabricated through citric acid sol-gel synthesis and spark plasma sintering (SPS). The citric acid sol-gel method provides molecular mixing for the preparation of precursor powders, which produces nanoscale and uniformly distributed Y2O3 particles in an ultrafine-grained Cu matrix. The effects of nanoscale Y2O3 particles on the microstructure, mechanical properties and thermal conductivity of the Cu-1wt.%Y2O3 alloy were investigated. The average grain size of the Cu-1wt.%Y2O3 alloy is 0.42 µm, while the average particle size of Y2O3 is 16.4 nm. The unique microstructure provides excellent mechanical properties with a tensile strength of 572 MPa and a total elongation of 6.4%. After annealing at 800 °C for 1 h, the strength of the alloy does not decrease obviously, showing excellent thermal stability. The thermal conductivity of Cu-1wt.%Y2O3 alloy is about 308 Wm-1K-1 at room temperature and it decreases with increasing temperature. The refined grain size, high strength and excellent thermal stability of Cu-1wt.%Y2O3 alloys can be ascribed to the pinning effects of nanoscale Y2O3 particles dispersed in the Cu matrix. The Cu-Y2O3 alloys with high strength and high thermal conductivity have potential applications in high thermal load components of fusion reactors.

The possible window of implantation for embryos in the first frozen embryo transplantation cycle: A retrospective analysis.

OBJECTIVE: This study aimed to investigate the duration of progesterone (P) therapy on clinical pregnancy rates as measured by the window of implantation (WOI) in the first cycle of frozen embryo transplantation. METHODS: The study compared the pregnancy rates between 345 cleavage stage transfers and 348 blastocyte transfers of frozen embryos with modified natural cycles in patients from July 1, 2020, to November 30, 2020. Four different P durations were analyzed in the cleavage stage embryo transfer group, i.e., two, three, four, and five days. Five different P durations were analyzed in the blastocyst transfer group, i.e., three, four, five, six, and seven days. RESULTS: The baseline demographics and clinical characteristics of the cleavage stage embryos and blastocyst transfer groups were not comparable. The clinical pregnancy rates following the cleavage stage embryo transfer after two, three, four, and five-day P administration were 45.71%, 44.60%, 38.40%, and 30.43%, respectively (the difference among the subgroups was not significant). Following the blastocyst transfer, the clinical pregnancy rates after three, four, five, six, and seven-day P administration were 50.65%, 63.51%, 60.00%, 54.55%, and 61.54%, respectively (the difference among the subgroups was not significant). In contrast, these two transfer groups showed significantly different clinical pregnancy rates following four and five-day P exposure (P < 0.05). CONCLUSION: For cleavage-stage embryo transfer, the most effective WOI was found between days two and five of P administration. The effective WOI for blastocyst transfer was observed between days three and seven of P administrations.

Microstructures and Tensile Properties of 9Cr-F/M Steel at Elevated Temperatures.

Tensile properties and microstructure changes under different stress states of tempered 9Cr-F/M steel were characterized using a transmission electron microscope (TEM), electron backscatter diffraction (EBSD), scanning electron microscopy (SEM), Vickers hardness tester, and tensile tester. This tempered steel has a typical lath martensite structure with only a few polygonal ferrites embedded, and M23C6 and MX phases nucleated on the lath boundaries or within the sub-grains. At elevated temperatures, the strength of the steel decreases. However, the elongation at 400 °C is lower than that at room temperature. For the necking zone, tensile deformation made the grain elongated to the direction of applied stress and thus the grain's cross-section becomes smaller. For samples with rectangular working area cross-section, the deformation in the TD direction was more severe than that in the ND direction, which made the grain elongated in the TD direction. These results can provide some guidance for composition optimization of the 9Cr-F/M steel and facilitate a better understanding of the fracture mechanism under different stress states.

Study on the Automatic Identification of ABX3 Perovskite Crystal Structure Based on the Bond-Valence Vector Sum.

Perovskite materials have a variety of crystal structures, and the properties of crystalline materials are greatly influenced by geometric information such as the space group, crystal system, and lattice constant. It used to be mostly obtained using calculations based on density functional theory (DFT) and experimental data from X-ray diffraction (XRD) curve fitting. These two techniques cannot be utilized to identify materials on a wide scale in businesses since they require expensive equipment and take a lot of time. Machine learning (ML), which is based on big data statistics and nonlinear modeling, has advanced significantly in recent years and is now capable of swiftly and reliably predicting the structures of materials with known chemical ratios based on a few key material-specific factors. A dataset encompassing 1647 perovskite compounds in seven crystal systems was obtained from the Materials Project database for this study, which used the ABX3 perovskite system as its research object. A descriptor called the bond-valence vector sum (BVVS) is presented to describe the intricate geometry of perovskites in addition to information on the usual chemical composition of the elements. Additionally, a model for the automatic identification of perovskite structures was built through a comparison of various ML techniques. It is possible to identify the space group and crystal system using just a small dataset of 10 feature descriptors. The highest accuracy is 0.955 and 0.974, and the highest correlation coefficient (R2) value of the lattice constant can reach 0.887, making this a quick and efficient method for determining the crystal structure.

Li2ZrO3-Coated Monocrystalline LiAl0.06Mn1.94O4 Particles as Cathode Materials for Lithium-Ion Batteries.

Li2ZrO3-coated and Al-doped micro-sized monocrystalline LiMn2O4 powder is synthesized through solid-state reaction, and the electrochemical performance is investigated as cathode materials for lithium-ion batteries. It is found that Li2ZrO3-coated LiAl0.06Mn1.94O4 delivers a discharge capacity of 110.90 mAhg-1 with 94% capacity retention after 200 cycles at room temperature and a discharge capacity of 104.4 mAhg-1 with a capacity retention of 87.8% after 100 cycles at 55 °C. Moreover, Li2ZrO3-coated LiAl0.06Mn1.94O4 could retain 87.5% of its initial capacity at 5C rate. This superior cycling and rate performance can be greatly contributed to the synergistic effect of Al-doping and Li2ZrO3-coating.

Effect of Nano-Y2O3 Content on Microstructure and Mechanical Properties of Fe18Cr Films Fabricated by RF Magnetron Sputtering.

In this work, FeCr-based films with different Y2O3 contents were fabricated using radio frequency (RF) magnetron sputtering. The effects of Y2O3 content on their microstructure and mechanical properties were investigated through scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), inductive coupled plasma emission spectrometer (ICP) and a nanoindenter. It was found that the Y2O3-doped FeCr films exhibited a nanocomposite structure with nanosized Y2O3 particles uniformly distributed into a FeCr matrix. With the increase of Y2O3 content from 0 to 1.97 wt.%, the average grain size of the FeCr films decreased from 12.65 nm to 7.34 nm, demonstrating a grain refining effect of Y2O3. Furthermore, the hardness of the Y2O3-doped FeCr films showed an increasing trend with Y2O3 concentration, owing to the synergetic effect of dispersion strengthening and grain refinement strengthening. This work provides a beneficial guidance on the development and research of composite materials of nanocrystalline metal with a rare earth oxide dispersion phase.

Wallenda-Nmo Axis Regulates Growth via Hippo Signaling.

Both Hippo signaling pathways and cell polarity regulation are critical for cell proliferation and the maintenance of tissue homeostasis, despite the well-established connections between cell polarity disruption and Hippo inactivation, the molecular mechanism by which aberrant cell polarity induces Hippo-mediated overgrowth remains underexplored. Here we use Drosophila wing discs as a model and identify the Wnd-Nmo axis as an important molecular link that bridges loss-of-cell polarity-triggered Hippo inactivation and overgrowth. We show that Wallenda (Wnd), a MAPKKK (mitogen-activated protein kinase kinase kinase) family member, is a novel regulator of Hippo pathways in Drosophila and that overexpression of Wnd promotes growth via Nemo (Nmo)- mediated Hippo pathway inactivation. We further demonstrate that both Wnd and Nmo are required for loss-of-cell polarity-induced overgrowth and Hippo inactivation. In summary, our findings provide a novel insight on how cell polarity loss contributes to overgrowth and uncover the Wnd-Nmo axis as an essential additional branch that regulates Hippo pathways in Drosophila.

Ultrahigh-order mode-assisted hybrid optoelectronic bistability with an ultralow threshold.

A hybrid optoelectronic bistability is realized with the assistance of an ultrahigh-order mode (UHM) excited in a symmetrical metal-cladding waveguide (SMCW). PMN-PT ceramics is selected as the guiding layer, which possesses the voltage modulated refractive index and thickness by means of an electro-optical effect and converse-piezoelectric effect. An amplified voltage signal translated from the intensity of reflected light is exerted on the guiding layer, whose parameter variations can alter the resonance condition of the UHM and finally lead to a dramatic change in the intensity of the reflected light. Since the full width at half-maximum of the UHM is extremely narrow, a hysteresis behavior with a milliwatt threshold between the incident light and the reflected light can be achieved when a positive feedback is established. Our bistability configuration is simple and not limited to TM polarization.

Partially Crystallized Ultrathin Interfaces between GaN and SiNx Grown by Low-Pressure Chemical Vapor Deposition and Interface Editing.

The formation mechanism of the partially crystallized ultrathin layer at the interface between GaN and SiNx grown by low-pressure chemical vapor deposition was analyzed based on the chemical components of reactants and products detected by high-resolution sputter depth profile analysis by X-ray photoelectron spectroscopy. A reasonable mass action equation for the formation of Si2N2O was proposed from the feasibility analysis of the Gibbs free energy changes of the reaction. The high-energy-activated Ga2O on the surface likely assists in the synthesis of the crystallized components. A well-defined 1ML θ-Ga2O3 transition interface was inserted into Si2N2O/GaN pure interface supercell slabs to edit the unsaturated state of the bonds. Low-density states can be achieved when the effective charges of the unsaturated atoms are adjusted to a certain interval.

Exploring the Two Coupled Conformational Changes That Activate the Munc18-1/Syntaxin-1 Complex.

Calcium-dependent synaptic vesicle exocytosis is mediated by SNARE complex formation. The transition from the Munc18-1/syntaxin-1 complex to the SNARE complex is catalyzed by the Munc13-1 MUN domain and involves at least two conformational changes: opening of the syntaxin-1 linker region and extension of Munc18-1 domain 3a. However, the relationship and the action order of the two conformational changes remain not fully understood. Here, our data show that an open conformation in the syntaxin-1 linker region can bypass the requirement of the MUN NF sequence. In addition, an extended state of Munc18-1 domain 3a can compensate the role of the syntaxin-1 RI sequence. Altogether, the current data strongly support our previous notion that opening of the syntaxin-1 linker region by Munc13-1 is a key step to initiate SNARE complex assembly, and consequently, Munc18-1 domain 3a can extend its conformation to serve as a template for association of synaptobrevin-2 and syntaxin-1.

Spatiotemporal Variation of Osmanthus fragrans Phenology in China in Response to Climate Change From 1973 to 1996.

Climate change greatly affects spring and autumn plant phenology around the world consequently, and significantly impacts ecosystem function and the social economy. However, autumn plant phenology, especially autumn flowering phenology, has not been studied so far. In this study, we examined the spatiotemporal pattern of Osmanthus fragrans phenology, including both leaf phenology (the date of bud-bust, BBD; first leaf unfolding, FLD; and 50% of leaf unfolding, 50 LD) and flowering phenology (the date of first flowering, FFD; peak of flowering, PFD; and end of flowering, EFD). Stepwise multiple linear regressions were employed to analyze the relationships between phenophases and climatic factors in the long term phenological data collected by the Chinese Phenological Observation Network from 1973 to 1996. The results showed that spring leaf phenophases and autumn flowering phenophases were strongly affected by latitude. BBD, FLD, and 50LD of O. fragrans were delayed by 3.98, 3.93, and 4.40 days as per degree of latitude increased, while FFD, PFD and EFD in O. fragrans advanced 3.11, 3.26, and 2.99 days, respectively. During the entire study period, BBD was significantly delayed across the region, whereas no significant trends were observed either in FLD or 50LD. Notably, all flowering phenophases of O. fragrans were delayed. Both leaf and flowering phenophases negatively correlated with growing degree-days (GDD) and cold degree-days (CDD), respectively. BBD and FLD were negatively correlated with total annual precipitation. In addition to the effects of climate on autumn flowering phenology, we found that earlier spring leaf phenophases led to delayed autumn flowering phenophases. Our results suggest that future climate change and global warming might delay the phenological sequence of O. fragrans. Our findings also advanced the flowering mechanism study of autumn flowering plants, and facilitated the accurate prediction of future phenology and climate change.