Rapid simulation of glycoprotein structures by grafting and steric exclusion of glycan conformer libraries.

Most membrane proteins are modified by covalent addition of complex sugars through N- and O-glycosylation. Unlike proteins, glycans do not typically adopt specific secondary structures and remain very mobile, shielding potentially large fractions of protein surface. High glycan conformational freedom hinders complete structural elucidation of glycoproteins. Computer simulations may be used to model glycosylated proteins but require hundreds of thousands of computing hours on supercomputers, thus limiting routine use. Here, we describe GlycoSHIELD, a reductionist method that can be implemented on personal computers to graft realistic ensembles of glycan conformers onto static protein structures in minutes. Using molecular dynamics simulation, small-angle X-ray scattering, cryoelectron microscopy, and mass spectrometry, we show that this open-access toolkit provides enhanced models of glycoprotein structures. Focusing on N-cadherin, human coronavirus spike proteins, and gamma-aminobutyric acid receptors, we show that GlycoSHIELD can shed light on the impact of glycans on the conformation and activity of complex glycoproteins.

A mosquito salivary protein-driven influx of myeloid cells facilitates flavivirus transmission.

Mosquitoes transmit many disease-relevant flaviviruses. Efficient viral transmission to mammalian hosts requires mosquito salivary factors. However, the specific salivary components facilitating viral transmission and their mechanisms of action remain largely unknown. Here, we show that a female mosquito salivary gland-specific protein, here named A. aegypti Neutrophil Recruitment Protein (AaNRP), facilitates the transmission of Zika and dengue viruses. AaNRP promotes a rapid influx of neutrophils, followed by virus-susceptible myeloid cells toward mosquito bite sites, which facilitates establishment of local infection and systemic dissemination. Mechanistically, AaNRP engages TLR1 and TLR4 of skin-resident macrophages and activates MyD88-dependent NF-κB signaling to induce the expression of neutrophil chemoattractants. Inhibition of MyD88-NF-κB signaling with the dietary phytochemical resveratrol reduces AaNRP-mediated enhancement of flavivirus transmission by mosquitoes. These findings exemplify how salivary components can aid viral transmission, and suggest a potential prophylactic target.

Optomechanical dissipative solitons.

Nonlinear wave-matter interactions may give rise to solitons, phenomena that feature inherent stability in wave propagation and unusual spectral characteristics. Solitons have been created in a variety of physical systems and have had important roles in a broad range of applications, including communications, spectroscopy and metrology1-4. In recent years, the realization of dissipative Kerr optical solitons in microcavities has led to the generation of frequency combs in a chip-scale platform5-10. Within a cavity, photons can interact with mechanical modes. Cavity optomechanics has found applications for frequency conversion, such as microwave-to-optical or radio-frequency-to-optical11-13, of interest for communications and interfacing quantum systems operating at different frequencies. Here we report the observation of mechanical micro-solitons excited by optical fields in an optomechanical microresonator, expanding soliton generation in optical resonators to a different spectral window. The optical field circulating along the circumference of a whispering gallery mode resonator triggers a mechanical nonlinearity through optomechanical coupling, which in turn induces a time-varying periodic modulation on the propagating mechanical mode, leading to a tailored modal dispersion. Stable localized mechanical wave packets-mechanical solitons-can be realized when the mechanical loss is compensated by phonon gain and the optomechanical nonlinearity is balanced by the tailored modal dispersion. The realization of mechanical micro-solitons driven by light opens up new avenues for optomechanical technologies14 and may find applications in acoustic sensing, information processing, energy storage, communications and surface acoustic wave technology.

Generic dynamic molecular devices by quantitative non-steady-state proton/water-coupled electron transport kinetics.

Dynamic molecular devices operating with time- and history-dependent performance raised new challenges for the fundamental study of microscopic non-steady-state charge transport as well as functionalities that are not achievable by steady-state devices. In this study, we reported a generic dynamic mode of molecular devices by addressing the transient redox state of ubiquitous quinone molecules in the junction by proton/water transfer. The diffusion limited slow proton/water transfer-modulated fast electron transport, leading to a non-steady-state transport process, as manifested by the negative differential resistance, dynamic hysteresis, and memory-like behavior. A quantitative paradigm for the study of the non-steady-state charge transport kinetics was further developed by combining the theoretical model and transient state characterization, and the principle of the dynamic device can be revealed by the numerical simulator. On applying pulse stimulation, the dynamic device emulated the neuron synaptic response with frequency-dependent depression and facilitation, implying a great potential for future nonlinear and brain-inspired devices.

Melatonin confers tolerance to nitrogen deficiency through regulating MdHY5 in apple plants.

Nitrogen (N) is an essential nutrient for crop growth and development, significantly influencing both yield and quality. Melatonin (MT), a known enhancer of abiotic stress tolerance, has been extensively studied. However, its relationship with nutrient stress, particularly N deficiency, and the underlying regulatory mechanisms of MT on N absorption remain unclear. In this study, exogenous MT treatment was found to improve the tolerance of apple plants to N deficiency. Apple plants overexpressing the MT biosynthetic gene N-acetylserotonin methyltransferase 9 (MdASMT9) were used to further investigate the effects of endogenous MT on low-N stress. Overexpression of MdASMT9 improved the light harvesting and heat transfer capability of apple plants, thereby mitigating the detrimental effects of N deficiency on the photosynthetic system. Proteomic and physiological data analyses indicated that MdASMT9 overexpression enhanced the trichloroacetic acid cycle and positively modulated amino acid metabolism to counteract N-deficiency stress. Additionally, both exogenous and endogenous MT promoted the transcription of MdHY5, which in turn bound to the MdNRT2.1 and MdNRT2.4 promoters and activated their expression. Notably, MT-mediated promotion of MdNRT2.1 and MdNRT2.4 expression through regulating MdHY5, ultimately enhancing N absorption. Taken together, these findings shed light on the association between MdASMT9-mediated MT biosynthesis and N absorption in apple plants under N-deficiency conditions.

TRANSPARENT TESTA GLABRA1 Regulates High-Intensity Blue Light-Induced Phototropism by Reducing CRYPTOCHROME1 Levels.

The asymmetrical distribution of auxin supports high intensity blue light (HBL)-mediated phototropism. Flavonoids, secondary metabolites induced by blue light and TRANSPARENT TESTA GLABRA1 (TTG1), alter auxin transport. However, the role of TTG1 in HBL-induced phototropism in Arabidopsis (Arabidopsis thaliana) remains unclear. We found that TTG1 regulates HBL-mediated phototropism. HBL-induced degradation of CRYPTOCHROME 1 (CRY1) was repressed in ttg1-1, and depletion of CRY1 rescued the phototropic defects of the ttg1-1 mutant. Moreover, overexpression of CRY1 in a cry1 mutant background led to phototropic defects in response to HBL. These results indicated that CRY1 is involved in the regulation of TTG1-mediated phototropism in response to HBL. Further investigation showed that TTG1 physically interacts with CRY1 via its N-terminus and that the added TTG1 promotes the dimerization of CRY1. The interaction between TTG1 and CRY1 may promote HBL-mediated degradation of CRY1. TTG1 also physically interacted with blue light inhibitor of cryptochrome 1 (BIC1) and Light-Response Bric-a-Brack/Tramtrack/Broad 2 (LRB2), and these interactions either inhibited or promoted their interaction with CRY1. Exogenous gibberellins (GA) and auxins, two key plant hormones that crosstalk with CRY1, may confer the recovery of phototropic defects in the ttg1-1 mutant and CRY1-overexpressing plants. Our results revealed that TTG1 participates in the regulation of HBL-induced phototropism by modulating CRY1 levels, which are coordinated with GA or IAA signaling.

HDAC1/2/3-mediated downregulation of neurogranin is involved in cognitive impairment in offspring exposed to maternal subclinical hypothyroidism.

Subclinical hypothyroidism (SCH) in pregnancy is the most common form of thyroid dysfunction in pregnancy, which can affect fetal nervous system development and increase the risk of neurodevelopmental disorders after birth. However, the mechanism of the effect of maternal subclinical hypothyroidism on fetal brain development and behavioral phenotypes is still unclear and requires further study. In this study, we constructed a mouse model of maternal subclinical hypothyroidism by exposing dams to drinking water containing 50 ppm propylthiouracil (PTU) during pregnancy and found that its offspring were accompanied by severe cognitive deficits by behavioral testing. Mechanistically, gestational SCH resulted in the upregulation of protein expression and activity of HDAC1/2/3 in the hippocampus of the offspring. ChIP analysis revealed that H3K9ac on the neurogranin (Ng) promoter was reduced in the hippocampus of the offspring of SCH, with a significant reduction in Ng protein, leading to reduced expression levels of synaptic plasticity markers PSD95 (a membrane-associated protein in the postsynaptic density) and SYN (synaptophysin, a specific marker for presynaptic terminals), and impaired synaptic plasticity. In addition, administration of MS-275 (an HDAC1/2/3-specific inhibitor) to SCH offspring alleviated impaired synaptic plasticity and cognitive dysfunction in offspring. Thus, our study suggests that maternal subclinical hypothyroidism may mediate offspring cognitive dysfunction through the HDAC1/2/3-H3K9ac-Ng pathway. Our study contributes to the understanding of the signaling mechanisms underlying maternal subclinical hypothyroidism-mediated cognitive impairment in the offspring.

Brusatol hinders the progression of bladder cancer by Chac1/Nrf2/SLC7A11 pathway.

Bladder cancer is a common tumor that impacts the urinary system and marked by a significant fatality rate and an unfavorable prognosis. Promising antineoplastic properties are exhibited by brusatol, which is obtained from the dried ripe fruit of Brucea javanica. The present study aimed to evaluate the influence of brusatol on the progression of bladder cancer and uncover the molecular mechanism involved. We used Cell Counting Kit-8, colony formation and EdU assays to detect cell numbers, viability and proliferation. We used transwell migration assay to detect cell migration ability. The mechanism of brusatol inhibition of bladder cancer proliferation was studied by flow cytometry and western blotting. It was revealed that brusatol could reduce the viability and proliferation of T24 and 5637 cells. The transwell migration assay revealed that brusatol was able to attenuate the migration of T24 and 5637 cells. We found that treatment with brusatol increased the levels of reactive oxygen species, malondialdehyde and Fe2+, thereby further promoting ferroptosis in T24 and 5637 cells. In addition, treatment with RSL3 (an agonistor of ferroptosis) ferrostatin-1 (a selective inhibitor of ferroptosis) enhanced or reversed the brusatol-induced inhibition. In vivo, treatment with brusatol significantly suppressed the tumor growth in nude mice. Mechanistically, brusatol induced ferroptosis by upregulating the expression of ChaC glutathione-specific gamma-glutamylcyclotransferase (Chac1) and decreasing the expression of SLC7A11 and Nrf2 in T24 and 5637 cells. To summarize, the findings of this research demonstrated that brusatol hindered the growth of bladder cancer and triggered ferroptosis via the Chac1/Nrf2/SLC7A11 pathway.

GR/Ahi1 regulates WDR68-DYRK1A binding and mediates cognitive impairment in prenatally stressed offspring.

Accumulating research shows that prenatal exposure to maternal stress increases the risk of behavioral and mental health problems for offspring later in life. However, how prenatal stress affects offspring behavior remains unknown. Here, we found that prenatal stress (PNS) leads to reduced Ahi1, decreased synaptic plasticity and cognitive impairment in offspring. Mechanistically, Ahi1 and GR stabilize each other, inhibit GR nuclear translocation, promote Ahi1 and WDR68 binding, and inhibit DYRK1A and WDR68 binding. When Ahi1 deletion or prenatal stress leads to hyperactivity of the HPA axis, it promotes the release of GC, leading to GR nuclear translocation and Ahi1 degradation, which further inhibits the binding of Ahi1 and WDR68, and promotes the binding of DYRK1A and WDR68, leading to elevated DYRK1A, reduced synaptic plasticity, and cognitive impairment. Interestingly, we identified RU486, an antagonist of GR, which increased Ahi1/GR levels and improved cognitive impairment and synaptic plasticity in PNS offspring. Our study contributes to understanding the signaling mechanisms of prenatal stress-mediated cognitive impairment in offspring.

Isoglutaminyl Cyclase Overexpression Enhances KYSE30 Cancer Cell Proliferation and Migration via the MAPK Signaling Pathway.

To understand how upregulated isoglutaminyl cyclase (isoQC) is involved in the initiation of diseases such as cancer, we developed a human KYSE30 carcinoma cell model in which isoQC was stably overexpressed. GO and KEGG analysis of the DEGs (228) and DEPs (254) respectively implicated isoQC on the proliferation invasion and metastasis of cells and suggested that isoQC might participate in the regulation of MAPK, RAS, circadian rhythm, and related pathways. At the functional level, isoQC-overexpressing KYSE30 cells showed enhanced proliferation, migration, and invasion capacity. Next, we decided to study the precise effect of isoQC overexpression on JNK, p-JNK, AKT, p-AKT, ERK, p-ERK, and PER2, as RNA levels of these proteins are significantly correlated with signal levels indicated in RNA-Seq analysis, and these candidates are the top correlated DEPs enriched in RT-qPCR analysis. We saw that only p-ERK expression was inhibited, while PER2 was increased. These phenotypes were inhibited upon exposure to PER2 inhibitor KL044, which allowed for the restoration of p-ERK levels. These data support upregulated isoQC being able to promote cancer cell proliferation and migration in vitro, likely by helping to regulate the MAPK and RAS signaling pathways, and the circadian protein PER2 might be a potential mediator.

A plant-specific SWR1 chromatin-remodeling complex couples histone H2A.Z deposition with nucleosome sliding.

Deposition of H2A.Z in chromatin is known to be mediated by a conserved SWR1 chromatin-remodeling complex in eukaryotes. However, little is known about whether and how the SWR1 complex cooperates with other chromatin regulators. Using immunoprecipitation followed by mass spectrometry, we found all known components of the Arabidopsis thaliana SWR1 complex and additionally identified the following three classes of previously uncharacterized plant-specific SWR1 components: MBD9, a methyl-CpG-binding domain-containing protein; CHR11 and CHR17 (CHR11/17), ISWI chromatin remodelers responsible for nucleosome sliding; and TRA1a and TRA1b, accessory subunits of the conserved NuA4 histone acetyltransferase complex. MBD9 directly interacts with CHR11/17 and the SWR1 catalytic subunit PIE1, and is responsible for the association of CHR11/17 with the SWR1 complex. MBD9, TRA1a, and TRA1b function as canonical components of the SWR1 complex to mediate H2A.Z deposition. CHR11/17 are not only responsible for nucleosome sliding but also involved in H2A.Z deposition. These results indicate that the association of the SWR1 complex with CHR11/17 may facilitate the coupling of H2A.Z deposition with nucleosome sliding, thereby co-regulating gene expression, development, and flowering time.

Polyvinyl Pyrrolidone Induced "Confinement Effect" on PbI2 and the Improvement on Crystallization and Thermal Stability of Perovskite.

Polyvinyl pyrrolidone is blended in PbI2 with varied concentration, so as to study the coarsening dynamics of perovskite during the two-step growth method. It is observed that polyvinyl pyrrolidone hinders the crystallization of PbI2 and helps to form a more amorphous PbI2 matrix, which then improves perovskite crystallization. As the blending concentration increases from 0 to 2 mM, average crystallite/grain size of perovskite increases from 40.29 nm/0.79 µm to 84.35 nm/1.02 µm while surface fluctuation decreases slightly from 25.64 to 23.96 nm. The observations are caused by the "confinement effect" brought by polyvinyl pyrrolidone on PbI2 . Elevating blending concentration of polyvinyl pyrrolidone results in smaller PbI2 crystallites and more amorphous PbI2 matrix, thus reducing the diffusion/reaction barrier between PbI2 and organic salt and favoring perovskite crystallization. As blending concentration increases from 0 to 2 mM, the device efficiency rises from 19.76 (± 0.60) % to 20.50 (± 0.89) %, with the optimized value up to 22.05%, which is further improved to 24.48% after n-Octylammonium iodide (OAI)-basing surface modification. The study enlarges the scope of "confinement effect" brought by polymer molecules, which is beneficial for efficient and stable perovskite solar cell fabrication.

Lipases secreted by a gut bacterium inhibit arbovirus transmission in mosquitoes.

Arboviruses are etiological agents of various severe human diseases that place a tremendous burden on global public health and the economy; compounding this issue is the fact that effective prophylactics and therapeutics are lacking for most arboviruses. Herein, we identified 2 bacterial lipases secreted by a Chromobacterium bacterium isolated from Aedes aegypti midgut, Chromobacterium antiviral effector-1 (CbAE-1) and CbAE-2, with broad-spectrum virucidal activity against mosquito-borne viruses, such as dengue virus (DENV), Zika virus (ZIKV), Japanese encephalitis virus (JEV), yellow fever virus (YFV) and Sindbis virus (SINV). The CbAEs potently blocked viral infection in the extracellular milieu through their lipase activity. Mechanistic studies showed that this lipase activity directly disrupted the viral envelope structure, thus inactivating infectivity. A mutation in the lipase motif of CbAE-1 fully abrogated the virucidal ability. Furthermore, CbAEs also exert lipase-dependent entomopathogenic activity in mosquitoes. The anti-arboviral and entomopathogenic properties of CbAEs render them potential candidates for the development of novel transmission control strategies against vector-borne diseases.

Experimental study of modified Tavis-Cummings model with directly-coupled superconducting artificial atoms.

The Tavis-Cummings model is intensively investigated in quantum optics and has important applications in generation of multi-atom entanglement. Here, we employ a superconducting circuit quantum electrodynamic system to study a modified Tavis-Cummings model with directly-coupled atoms. In our device, three superconducting artificial atoms are arranged in a chain with direct coupling through fixed capacitors and strongly coupled to a transmission line resonator. By performing transmission spectrum measurements, we observe different anticrossing structures when one or two qubits are resonantly coupled to the resonator. In the case of the two-qubit Tavis-Cummings model without qubit-qubit interaction, we observe two dips at the resonance point of the anticrossing. The splitting of these dips is determined by Δ λ=2g12+g32, where g1 and g3 are the coupling strengths between Qubit 1 and the resonator, and Qubit 3 and the resonator, respectively. The direct coupling J12 between the two qubits results in three dressed states in the two-qubit Tavis-Cummings model at the frequency resonance point, leading to three dips in the transmission spectrum. In this case, the distance between the two farthest and asymmetrical dips, arising from the energy level splitting, is larger than in the previous case. The frequency interval between these two dips is determined by the difference in eigenvalues (Δ λ=ε 1+-ε 1-), obtained through numerical calculations. What we believe as novel and intriguing experimental results may potentially advance quantum optics experiments, providing valuable insights for future research.

Development and validation of a novel preoperative clinical model for predicting lymph node metastasis in perihilar cholangiocarcinoma.

BACKGROUD: We aimed to develop a novel preoperative nomogram to predict lymph node metastasis (LNM) in perihilar cholangiocarcinoma (pCCA) patients. METHODS: 160 pCCA patients were enrolled at Lihuili Hospital from July 2006 to May 2022. A novel nomogram model was established to predict LNM in pCCA patients based on the independent predictive factors selected by the multivariate logistic regression model. The precision of the nomogram model was evaluated through internal and external validation with calibration curve statistics and the concordance index (C-index). Receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to evaluate and determine the clinical utility of the nomogram. RESULTS: Multivariate logistic regression demonstrated that age (OR = 0.963, 95% CI: 0.930-0.996, P = 0.030), CA19-9 level (> 559.8 U/mL vs. ≤559.8 U/mL: OR = 3.162, 95% CI: 1.519-6.582, P = 0.002) and tumour diameter (OR = 1.388, 95% CI: 1.083-1.778, P = 0.010) were independent predictive factors of LNM in pCCA patients. The C-index was 0.763 (95% CI: 0.667-0.860) and 0.677 (95% CI: 0.580-0.773) in training cohort and validation cohort, respectively. ROC curve analysis indicated the comparative stability and adequate discriminative ability of nomogram. The sensitivity and specificity were 0.820 and 0.652 in training cohort and 0.704 and 0.649 in validation cohort, respectively. DCA revealed that the nomogram model could augment net benefits in the prediction of LNM in pCCA patients. CONCLUSIONS: The novel prediction model is useful for predicting LNM in pCCA patients and showed adequate discriminative ability and high predictive accuracy.

Neighboring mutation-mediated enhancement of dengue virus infectivity and spread.

Frequent turnover of dengue virus (DENV) clades is one of the major forces driving DENV persistence and prevalence. In this study, we assess the fitness advantage of nine stable substitutions within the envelope (E) protein of DENV serotypes. Two tandem neighboring substitutions, threonine to lysine at the 226th (T226K) and glycine to glutamic acid at the 228th (G228E) residues in the DENV2 Asian I genotype, enhance virus infectivity in either mosquitoes or mammalian hosts, thereby promoting clades turnover and dengue epidemics. Mechanistic studies indicate that the substitution-mediated polarity changes in these two residues increase the binding affinity of E for host C-type lectins. Accordingly, we predict that a G228E substitution could potentially result in a forthcoming epidemic of the DENV2 Cosmopolitan genotype. Investigations into the substitutions associated with DENV fitness in hosts may offer mechanistic insights into dengue prevalence, thus providing a warning of potential epidemics in the future.

Selective Construction of C-S/S-N Bonds from N-Substituted O-Thiocarbamates and Indoles under Transition-Metal-Free Conditions.

A method for the selective construction of S-N/C(sp2)-S bonds using N-substituted O-thiocarbamates and indoles as substrates is reported. This protocol features good atom utilization, mild conditions, short reaction time, and wide substrate scope, which can provide a convenient path for the functionalization of indoles. In addition, the reaction could be scaled up on gram scale, showing potential application value in industry synthesis.

Functional and safety outcomes after benign prostatic enlargement surgeries in men with detrusor underactivity compared with normal detrusor contractility: Systematic review and meta-analysis.

INTRODUCTION: Men with detrusor underactivity (DUA) and concomitant bladder outlet obstruction (BOO) due to benign prostatic enlargement (BPE) may present poorer functional outcomes after surgical desobstruction. This study aimed to evaluate the safety and efficacy of BPE surgery in men with DUA compared with those with normal detrusor contractility (NC). MATERIALS AND METHODS: This review was performed according to the 2020 PRISMA framework. A comprehensive literature search was performed until May 7, 2023, using MEDLINE, EMBASE, and Cochrane Database. No date limits were imposed. Only comparative studies were accepted. The primary endpoint was to assess if there was any difference in short- and long-term functional outcomes after BPE surgery in men with DUA and NC. The secondary endpoint was to evaluate the differences in perioperative outcomes and postoperative complications between the two groups. Meta-analysis was performed using Review Manager (RevMan) software. RESULTS: There were 5 prospective nonrandomized studies and 12 retrospective studies, including 1701 DUA and 1993 NC patients. Regarding surgical procedures, there were eight TURP (transurethral resection of the prostate) studies, four GreenLight PVP (photoselective vaporization of the prostate) studies, two HoLEP (Holmium laser enucleation of the prostate) studies, one GreenLight PVP/HoLEP study, one Holmium laser incision of the prostate study, and one study did not report the type of surgery. We did not find a statistically significant difference between the two groups in terms of perioperative outcomes, including postoperative catheterization time, hospitalization time, urinary retention, need to recatheterization, transfusion rate, or urinary tract infections. Also, we found no significant differences in long-term complications, such as bladder neck stenosis or urethral stenosis. Posttreatment bladder recatheterization and retreatment rate for BPE regrowth could not be evaluated properly, because only one study reported these findings. When we analyzed functional outcomes at 3 months, those with NC had lower International Prostatic Symptom Score (IPSS), lower quality-of-life (QoL) score, better maximum flow rate (Qmax), and lower post-voiding residual (PVR) of urine. These results were maintained at 6 months postoperatively, with exception of PVR that showed no difference. However, at 12 and more than 12 months the functional outcomes became similar regarding IPSS and QoL. There were few data about Qmax and PVR at longer follow-up. CONCLUSION: In this meta-analysis, data suggest that BOO surgical treatment in patients with concomitant BPE and DUA appears to be safe. Despite patients with DUA may present worse functional outcomes in the short postoperative term compared with the NC population, IPSS and QoL scores become comparable again after a longer follow-up period after surgery.

Reply to the 'Comment on "A single level tunneling model for molecular junctions: evaluating the simulation methods"' by I Baldea, Phys. Chem. Chem. Phys., 2024, 26, D2CP05110A (http://D2CP05110A).

We respond to the recent comment by Dr. Ion Bâldea concerning our work, "A single level tunneling model for molecular junctions: evaluating the simulation methods [E. M. Opodi et al.,Phys. Chem. Chem. Phys., 2022, 24, 11958]". Dr. Bâldea has raised concerns about the applicability map we developed based on the comparison study of the 3 analytical models used in the study of molecular electronics. In our response, we have dissected Dr. Bâldea's critique into four primary points. For each, we have provided comprehensive replies that address and rectify the misinterpretations of our initial study. We'd like to thank Dr. Ion Bâldea for his comments, which have resulted in further clarification of the applicability of the analytical models for the study of molecular electronics.

Auxiliary Rather Than Dominant. The Role of Direct Dy-S Coordination in Single-Molecule Magnet Unveiled via ab initio Study.

The role of Dy-S coordination in a single-molecule magnet (SMM) is investigated via an ab initio study in a group of mononuclear structures. The SMM performance of this group is well interpreted via a concise criterion consisting of long quantum tunneling of magnetization (QTM) time τQTM and high effective barrier for magnetic reversal Ueff. The best SMMs in the selected group, i.e., 1Dy (CCDC refcode: PUKFAF) and 2Dy (CCDC refcode: NIKSEJ), are just those holding the longest τQTM and the highest Ueff simultaneously. Further analysis based on the crystal field model and ab initio magneto-structural exploration indicates that the influence of Dy-S coordination on the SMM performance of 1Dy is weaker than that of axial Dy-O coordination. Thus, Dy-S coordination is more likely to play an auxiliary role rather than a dominant one. However, if placed at the suitable equatorial position, Dy-S coordination could provide important support for good SMM performance. Consequently, starting from 1Dy, we built two new structures where Dy-S coordination only exists at the equatorial position and two axial positions are occupied by strong Dy-O/Dy-F coordination. Compared to 1Dy and 2Dy, these new ones are predicted to have significantly longer τQTM and higher Ueff, as well as a nearly doubled blocking temperature TB. Thus, they are probable candidates of SMM having clearly improved performance.