Molecular Level Research Articles

High capacities of carbon capture and photosynthesis of a novel organic carbon-fixing microalgae in municipal wastewater: From mutagenesis, screening, ability evaluation to mechanism analysis

The development of wastewater treatment processes capable of reducing and fixing carbon is currently a hot topic in the wastewater treatment field. Microalgae possess a natural carbon-fixing advantage, and microalgae that can symbiotically coexist with indigenous bacteria in actual wastewater attract more significant attention. Ultraviolet (UV) mutagenesis and dissolved organic carbon (DOC) acclimation were applied to strengthen the carbon-fixing performance of microalgae in this study. The mechanisms associated with microalgal water purification ability, gene regulation at the molecular level and photosynthetic potential under different trophic modes resulting from carbon fixation and transformation were disclosed. The superior performance of Chlorella sp. MHQ2 was eventually screened out among a large number of mutants generated from 3 wild-type Chlorella strains. Results indicated that the dry cell weight of the optimal species Chlorella sp. HQ mutant MHQ2 was 1.91 times that of the wild strain in the pure algal system, more carbon from municipal wastewater (MW) were transferred to the microalgae and re-entered into the biological cycle through resource utilization. In addition, COD, NH3-N and TP removal efficiencies of MW by Chlorella sp. MHQ2 were found to increase to 95.8% (1.1-times), 96.4% (1.4-times), and 92.9% (1.2-times), respectively, under the extra DOC supply and the assistance of indigenous bacteria in the MW. In the transcriptome analysis of the logarithmic phase, the glycolytic pathway was inhibited, and the pentose phosphate pathway was mainly carried out for microalgal life activities, further promoting efficient energy utilization. Upon analysis of carbon capture capacity and photosynthetic potential in trophic mode, the addition of NaHCO3 increased the photosynthetic rate of Chlorella sp. MHQ2 in mixotrophy whereas it was attenuated in autotrophy. This study could provide a new perspective for the study of resource utilization and microalgae carbon- fixing mechanisms in the actual wastewater treatment process.

A self-driven multifunctional microfluidic sweat analysis system for efficient sweat collection and real-time monitoring

Wearable sweat sensors offer the opportunity for non-invasive and real-time monitoring of metabolite information in sweat, enabling individuals to dynamically monitor their physiology states at the molecular level. However, sweat possesses characteristics such as small volume, volatility, susceptibility to epidermal contamination, and low analyte concentrations, making its reliable collection and detection challenge for wearable sweat sensors. In this work, we develop a self-driven multifunctional microfluidic sweat analysis system (SMMSAS) for efficient sweat collection and detection. The SMMSAS features with a wetting contrast for the sweat, which comprises superhydrophobic inlet, superhydrophilic microchannel enriched with nanofiber, and an absorbent test paper. Such a feature enables the spontaneous sweat transports in the form of dropwise due to the exertion of “Laplace force-capillary force-capillary force” on sweat, thereby facilitating the real-time sweat detection. SMMSAS integrated with the functions of impedance and colorimetry analysis is able to simultaneously record the multiple information in sweat, including sweat volume, sweating rate, total electrolyte concentration, glucose concentration, and pH value, all of which are important to reflect the physiological state of the human body. We also demonstrate the capability of SMMSAS in real-time monitoring the sweating conditions of the human body, which is attributed to its fast responsiveness (∼ 100 ms) for the wide range sweating rate (0.5−15 μL/min) and various total electrolyte concentration (0−80 mM), paving the way for next-generation personalized healthcare.

Candidate membrane protein gene families related to chemoreception in a wood-boring beetle, Pharsalia antennata Gahan (Coleoptera: Cerambycidae)

The longhorned beetles are key players for the maintenance of biodiversity in the terrestrial ecosystem. As xylophagous cerambycid insects in Coleoptera, the beetles have evolved specialized olfactory and gustatory systems to recognize chemical cues in the surrounding habitats. Despite over 36,000 described species in the Cerambycidae family including a wood-boring pest Pharsalia antennata, only a limited number of them (<1 %) have been characterized regarding their chemical ecology at the molecular level. Here, we surveyed four membrane protein gene families in P. antennata related to chemoreception through transcriptomics, phylogenetics and expression profiling analyses. In total, 144 genes encoding 72 odorant receptors (ORs), 33 gustatory receptors (GRs), 23 ionotropic receptors (IRs), four sensory neuron membrane proteins (SNMPs) and 12 ionotropic glutamate receptors (iGluRs) were harvested from the transcriptome of multiple tissues including antennae and legs of both sexes. The lineage-specific expansion of PantORs possibly implied a diverse range of host plants in this beetle, supporting this correlation between the host range and olfactory receptor repertoire sizes across cerambycid species. Further phylogenetic analysis revealed that Group 2 was contributed mainly to the large OR gene repertoire in P. antennata, representing 18 genes in Group 2A and eight in Group 2B. On the other hand, some key chemosensory genes were identified by applying a phylogenetics approach, such as PantOR21 close to the 2-phenylethanol receptor in Megacyllene caryae, three carbon dioxide GRs and seven Antennal IRs (A-IRs) clades. We also determined sex- and tissue-specific expression profiles of 69 chemosensory genes, revealing the high expression of most PantORs in antennae. Noticeably, 10 sex-biased genes (six PantORs, three PantIRs and PantSNMP1a) were presented in antennae, five sex-biased PantGRs in legs and 39 sex-biased genes (15 PantORs, 13 PantGRs, eight PantIRs and three PantSNMPs) in abdomens. These findings have greatly enhanced our knowledge about the chemical ecology of P. antennata and identify candidate molecular targets for mediating smell and taste of this beetle.

Evaluation of surfactant-aided polycyclic aromatic hydrocarbon biodegradation by molecular docking and molecular dynamic simulation in the marine environment

Marine oil spills directly cause polycyclic aromatic hydrocarbons (PAHs) pollution and affect marine organisms due to their toxic property. Chemical and bio-based dispersants composed of surfactants and solvents are considered effective oil spill-treating agents. Dispersants enhance oil biodegradation in the marine environment by rapidly increasing their solubility in the water column. However, the effect of dispersants, especially surfactants, on PAHs degradation by enzymes produced by microorganisms has not been studied at the molecular level. The role of the cytochrome P450 (CYP) enzyme in converting contaminants into reactive metabolites during the biodegradation process has been evidenced, but the activity in the presence of surfactants is still ambiguous. Thus, this study focused on the evaluation of the impact of chemical and bio-surfactants (i.e., Tween 80 (TWE) and Surfactin (SUC)) on the biodegradation of naphthalene (NAP), chrysene (CHR), and pyrene (PYR), the representative components of PAHs, with CYP enzyme from microalgae Parachlorella kessleri using molecular docking and molecular dynamics (MD) simulation. The molecular docking analysis revealed that PAHs bound to residues at the CYP active site through hydrophobic interactions for biodegradation. The MD simulation showed that the surfactant addition changed the enzyme conformation in the CYP-PAH complexes to provide more interactions between the enzyme and PAHs. This led to an increase in the enzyme's capability to degrade PAHs. Binding free energy (ΔG‌‌Bind) calculations confirmed that surfactant treatment could enhance PAHs degradation by the enzyme. The SUC gave a better result on NAP and PYR biodegradation based on ΔG‌‌Bind, while TWE facilitated the biodegradation of CHR. The research outputs could greatly facilitate evaluating the behaviors of oil spill-treating agents and oil spill response operations in the marine environment.

Theoretical calculations and molecular modelling of isoindoline compounds as anticonvulsant agents

The lack of safe and effective antiepileptic drugs is a persistent issue that could be addressed through the repurposing or further development of commonly available drugs. Due to high accuracy, low effort, and high cost, it is best to begin the search for alternative treatments with a theoretical chemical study. Isoindoline derivatives, their ΔG, and their molecular docking were subjected to the molecular level theory. Having a ΔG of -4.9, compound A1 demonstrated a unique activity against protein 1OHV (4-aminobutyrate-aminotransferase; from pig), while the same compound demonstrated distinct activity against protein 3F8E (coumarins as suicide carbonic anhydrase inhibitors) with a ΔG of -4.533. Moreover, compound A3 exhibited a unique activity against protein 6KZP (calcium channel-ligand) with a ΔG of -7.597. The undertaken DFT analysis determined the highest occupied molecular orbital (HOMO), the least unoc¬cupied molecular orbital (LUMO), and the HOMO-LUMO gap values for the studied derivatives (compound A1: -0.202, -0.091, and -0.111 eV; compound A3: -0.228, -0.102, and -0.126 eV, respectively). The ionization potential, the soft¬ness, the hardness, and other chemical properties of these compounds were subsequently computed. Drug likeness predictions were employed in order to show that the compounds adhered to Lipinski’s rule. Our results indicate that the molecular mass, log P, as well as the hydrogen bonding donors and acceptors of the herein assessed isoindoline compounds fall within acceptable ranges.

Analysis of the mechanism of resistance to enzymatic hydrolysis of RS-5 resistant starch

RS-5 refers to the resistant starch formed by complexation of starch molecules with other molecules. In this study, the molecular mechanism of RS-5 was analysed. First, it was found, when α-amylase acted on the starch-lipid complexes, the glucose residues involved in complexation cannot be hydrolyzed by α-amylase, while the glucose residues not directly involved in complexation can be hydrolyzed. Second, lipid molecules are not necessary for the formation of RS-5 and can be replaced with small peptides or decanal molecules. Considering the multiple health hazards that may result from excessive lipid intake, small peptides composed of essential amino acids may be more desirable materials for RS-5 preparation. Third, starch-lipid complexes had strong interactions with α-amylase, which provides evidence in support of the sliding continuum hydrolysis hypothesis of α-amylase. These results revealed the mechanism of RS-5 at the molecular level, which provides a reference for the production and research of RS-5.

Unveiling the molecular mechanisms of size-dependent effect of polystyrene micro/nano-plastics on Chlamydomonas reinhardtii through proteomic profiling

Microplastics have become a prevalent environmental pollutant due to widespread release and production. Algae, as primary producers, play a crucial role in maintaining the ecological balance of freshwater environments. Despite reports on the inhibition of microalgae by microplastics, the size-dependent effects on microalgae and associated molecular mechanism remain poorly understood. This study investigates the impacts of three polystyrene micro/nano-plastics (PS-MNPs) with different sizes (100 nm, 350 nm, and 6 μm) and concentrations (25–200 mg/L) on Chlamydomonas reinhardtii (C. reinhardtii) throughout its growth period. Results reveal size- and concentration-dependent growth inhibition and induction of oxidative stress by PS-MNPs, with microalgae exhibiting increased vulnerability to smaller-sized and higher-concentration PS-MNPs. Proteomics analysis elucidates the size-dependent suppression of proteins involved in the photosynthesis process by PS-MNPs. Photosynthetic activity assays demonstrate that smaller PS-MNPs more significantly reduce chlorophyll content and the maximal photochemical efficiency of photosystem II. Finally, electron microscope and Western blot assays collectively confirm the size effect of PS-MNPs on microalgae growth is attributable to suppressed protein expression rather than shading effects. This study contributes to advancing our understanding of the intricate interactions between micro/nano-plastics and algae at the molecular level, emphasizing the efficacy of proteomics in dissecting the mechanistic aspects of microplastics-induced biological effects on environmental indicator organisms.

Unveiling potential of thiophene-functionalized C3N3 nanosheet as an anode for Li-ion batteries: A DFT-D3 study

Covalent triazine frameworks (CTFs) are a fascinating type of porous organic materials that exhibit numerous distinct features, such as significant specific surface area, outstanding chemical/thermal stability, and structural modifiability at the molecular level. These features make CTFs highly appealing for utilization in Li-ion batteries (LIBs). However, their low electronic conductivity limits their practical applications. In the present study, the potential anode application of thiophene-functionalized C3N3 nanosheet for LIBs was conducted by dispersion-corrected density functional theory (DFT-D3) calculations. It was found that functionalization of the C3N3 nanosheet with six thiophene groups ((THP)6@C3N3) led to the highest reduction (0.19 eV) in the energy gap of the pristine C3N3 nanosheet. A single Li-ion preferably adsorbs between two nitrogen atoms of the triazine ring with an adsorption energy of about 4.59 eV. The absorption of Li-ion resulted in a reduction of the band gap from 1.37 eV to 0.43 eV, indicating enhanced electrical conductivity and superior cycle stability. The fully loaded functionalized nanosheet with nineteen Li-ions at various adsorption sites exhibited a remarkable theoretical specific capacity of 526.55 mAh/g. This configuration also displayed a low open-circuit voltage (0.09 V) and diffusion energy barrier (0.35 eV), ideal as an anode with a rapid charging/discharging rate. Therefore, thiophene-functionalized C3N3 nanosheet demonstrates superior anode performance for LIBs due to its high theoretical specific capacity, small diffusion barrier, and low working voltage. This work can provide insights for the refere development of CTF-based anode materials.

Spin-State Control in Dysprosium(III) Metallacrown Magnets via Thioacetal Modification.

Integrating controllable spin states into single-molecule magnets (SMMs) enables precise manipulation of magnetic interactions at a molecular level, but remains a synthetic challenge. Herein, we developed a 3d-4f metallacrown (MC) magnet [DyNi5(quinha)5(Clsal)2(py)8](ClO4)∙4H2O (H2quinha = quinaldichydroxamic acid, HClsal = 5-chlorosalicylaldehyde) wherein a square planar NiII is stabilized by chemical stacking. Thioacetal modification was employed via post-synthetic ligand substitutions and yielded [DyNi5(quinha)5(Clsaldt)2(py)8](ClO4)·3H2O (HClsaldt = 4-chloro-2-(1,3-dithiolan-2-yl)phenol). Thanks to the additional ligations of thioacetal onto the NiII site, coordination-induced spin state switching (CISSS) took place with spin state altering from low-spin S = 0 to high-spin S = 1. The synergy of CISSS effect and magnetic interactions results in distinct energy splitting and magnetic dynamics. Magnetic studies indicate prominent enhancement of reversal barrier from 57 cm-1 to 423 cm-1, along with hysteresis opening and an over 200-fold increment in coercive field at 2 K. Ab initio calculations provide deeper insights into the exchange models and rationalize the relaxation/tunnelling pathways. These results demonstrate here provide a fire-new perspective in modulating the magnetization relaxation via the incorporation of controllable spin states and magnetic interactions facilitated by the CISSS approach.

Spin‐State Control in Dysprosium(III) Metallacrown Magnets via Thioacetal Modification

Integrating controllable spin states into single‐molecule magnets (SMMs) enables precise manipulation of magnetic interactions at a molecular level, but remains a synthetic challenge. Herein, we developed a 3d‐4f metallacrown (MC) magnet [DyNi5(quinha)5(Clsal)2(py)8](ClO4)∙4H2O (H2quinha = quinaldichydroxamic acid, HClsal = 5‐chlorosalicylaldehyde) wherein a square planar NiII is stabilized by chemical stacking. Thioacetal modification was employed via post‐synthetic ligand substitutions and yielded [DyNi5(quinha)5(Clsaldt)2(py)8](ClO4)·3H2O (HClsaldt = 4‐chloro‐2‐(1,3‐dithiolan‐2‐yl)phenol). Thanks to the additional ligations of thioacetal onto the NiII site, coordination‐induced spin state switching (CISSS) took place with spin state altering from low‐spin S = 0 to high‐spin S = 1. The synergy of CISSS effect and magnetic interactions results in distinct energy splitting and magnetic dynamics. Magnetic studies indicate prominent enhancement of reversal barrier from 57 cm−1 to 423 cm−1, along with hysteresis opening and an over 200‐fold increment in coercive field at 2 K. Ab initio calculations provide deeper insights into the exchange models and rationalize the relaxation/tunnelling pathways. These results demonstrate here provide a fire‐new perspective in modulating the magnetization relaxation via the incorporation of controllable spin states and magnetic interactions facilitated by the CISSS approach.

Endothelial dysfunction in neurodegenerative disease: Is endothelial inflammation an overlooked druggable target?

Neurological diseases with a neurodegenerative component have been associated with alterations in the cerebrovasculature. At the anatomical level, these are centred around changes in cerebral blood flow and vessel organisation. At the molecular level, there is extensive expression of cellular adhesion molecules and increased release of pro-inflammatory mediators. Together, these has been found to negatively impact blood-brain barrier integrity. Systemic inflammation has been found to accelerate and exacerbate endothelial dysfunction, neuroinflammation and degeneration. Here, we review the role of cerebrovasculature dysfunction in neurodegenerative disease and discuss the potential contribution of intermittent pro-inflammatory systemic disease in causing endothelial pathology, highlighting a possible mechanism that may allow broad-spectrum therapeutic targeting in the future.

Photobiomodulation of Gingival Cells Challenged with Viable Oral Microbes.

The oral cavity, a unique ecosystem harboring diverse microorganisms, maintains health through a balanced microflora. Disruption may lead to disease, emphasizing the protective role of gingival epithelial cells (GECs) in preventing harm from pathogenic oral microbes. Shifting GECs' response from proinflammatory to antimicrobial could be a novel strategy for periodontitis. Photobiomodulation therapy (PBMT), a nonpharmacologic host modulatory approach, is considered an alternative to drugs. While the host cell response induced by a single type of pathogen-associated molecular patterns (PAMPs) was widely studied, this model does not address the cellular response to intact microbes that exhibit multiple PAMPs that might modulate the response. Inspired by this, we developed an in vitro model that simulates direct interactions between host cells and intact pathogens and evaluated the effect of PBMT on the response of human gingival keratinocytes (HGKs) to challenge viable oral microbes at both the cellular and molecular levels. Our data demonstrated that LED pretreatment on microbially challenged HGKs with specific continuous wavelengths (red: 615 nm; near-infrared: 880 nm) induced the production of various antimicrobial peptides, enhanced cell viability and proliferation, promoted reactive oxygen species scavenging, and down-modulated proinflammatory activity. The data also suggest a potential explanation regarding the superior efficacy of near-infrared light treatment compared with red light in enhancing antimicrobial activity and reducing cellular inflammation of HGKs. Taken together, the findings suggest that PBMT enhances the overall barrier function of gingival epithelium while minimizing inflammation-mediated breakdown of the underlying structures.

The Role of Speedy/RINGO Protein in Breast Cancer as a Future Biomarker.

Cyclin-dependent kinases (CDKs) are proteins that require the binding of regulatory subunits called cyclins and play a key role in cell cycle progression and activation. CDKs play a key role in carcinogenesis of many solid malignancies, and inhibition of these proteins has produced anti-cancer effects demonstrated in preclinical studies. This narrative review was conducted to develop a hypothetical approach to determine whether Speedy/RINGO, a protein associated with CDK2, could be a possible predictive factor in breast cancer patients treated with a CDK4/6 inhibitor. A literature search was conducted in PubMed, Web of Science, Medline, and Google Scholars search engines to match the following words: "Speedy/RINGO" or "Spy1" and "CDKs" or "Cyclin-dependent kinases (CDKs)" and "CDK4/6 inhibitors" and "Regulation" and "Molecular" and "Breast cancer" and "Carcinogenesis". Only articles investigating the relationship between the Speedy/RINGO protein and CDKs at the molecular level were included. Literature information was compiled by trying to establish a relationship with our hypothesis question. Speedy/RINGO is a tightly regulated proto-oncogenic mammalian protein playing important roles in the somatic cell cycle. Studies have emphasized that although it does not have amino acid sequence homology with cyclins, it can activate CDK2. In addition, results showing molecular compensation of CDK4/6 inhibition through CDK2 activation, also showed that CDK2 can predict drug resistance. Another important finding was that overexpressed Speedy/RINGO, during CDK4/6 inhibitor treatment, could strongly activate CDK2, resulting in a negative response to treatment. Although many predictive factors have been investigated to indicate response to CDK4/6 inhibitors or determine drug resistance, a consensus biomarker has yet to be established. In light of the information obtained from our review, it can be concluded that the Speedy/RINGO protein may have an important role as a predictive biomarker in terms of response to treatment, continuity of treatment and drug resistance in patients treated with CDK4/6 inhibitors.

A Molecular Expression for "Line Tension".

"Line tension", a concept that features in an additional term to the Young's equation, was introduced to describe the size dependence of contact angles of nanodroplets on surfaces. Although this concept describes the observations in a succinct, elegant manner, theorists have long had misgivings about the physical interpretation of the phenomenon. Papers have been published that attempt to nail down its value, which is reportedly very small (∼10 pN) and evidently even the sign has been uncertain. Attempts to interpret it in a mechanical manner analogous to interfacial tension, i.e., due to the curvature of the three-phase contact line, have run into conceptual problems that require invocations of ever more complex models. In this work, we have used molecular simulations to systematically relate "line tension" to the additional free energy per unit length of the three-phase line and found no direct relation. However, when we rederived the Young's equation without ignoring the interfacial molecules, we found a physically satisfying explanation for the size dependence of the contact angle of nanodroplets without invoking the curvature of the three-phase contact line. The new model does not have the elegant form of the modified Young's equation, but each parameter in it has an unambiguous physical interpretation. An approximate form of this model, linearized in the inverse droplet radius, yields a quantity that is mathematically analogous to what is conventionally called "line tension", but unpacked at the molecular level, showing that it is unrelated to a restoring force associated with the curvature of the macroscopic three-phase contact line.

Evaluation of genotoxic effect via expression of DNA damage responsive gene induced by ivermectin on MDBK cell line.

Ivermectin (IVM) is an anti-parasitic drug which is used for treating parasitic infestations. It has been used in humans for treating intestinal strongyloidiasis and onchocerciasis however, currently researchers are investigating its potential for treating coronavirus SARS-CoV-2. Due to its broad-spectrum activities, IVM is being used excessively in animals which has generated an interest for researchers to investigate its toxic effects. Cytotoxic and genotoxic effects have been reported in animals due to excessive usage of IVM. Therefore, this study aims to evaluate the cytotoxic and genotoxic effects of IVM on the Madin-Darby-Bovine-Kidney (MDBK) cell line by examining the expression of a DNA damage-responsive gene (OGG1). Cytotoxicity of IVM was tested using an assay (MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), whereas the genotoxicity was evaluated using comet assay along with micronucleus assay. Moreover, the gene expression of DNA damage response gene (OGG1) was measured by qRT-PCR, after extraction of RNA from the MDBK cell line using the TRIzol method and its conversion to cDNA by reverse-transcriptase PCR. During the experiment, cell viability percentage was measured at different doses of IVM i.e., 25%, 50%, 75%, along with LC50/2, LC50 and LC50*2. It was observed that the gene expression of OGG1 increased as the concentration of IVM increased. It was concluded that IVM has both cytotoxic and genotoxic effects on the MDBK cell line. Furthermore, it is recommended that studies related to the toxic effects of IVM at molecular level and on other model organisms should be conducted to combat its hazardous effects.

Therapeutic doses of ketamine acutely attenuate the aversive effect of losses during decision-making.

The discovery of rapid-acting antidepressant, ketamine has opened a pathway to a new generation of treatments for depression, and inspired neuroscientific investigation based on a new perspective that non-adaptive changes in the intrinsic excitatory and inhibitory circuitry might underlie the pathophysiology of depression. Nevertheless, it still remains largely unknown how the hypothesized molecular and synaptic levels of changes in the circuitry might mediate behavioral and neuropsychological changes underlying depression, and how ketamine might restore adaptive behavior. Here, we used computational models to analyze behavioral changes induced by therapeutic doses of ketamine, while rhesus macaques were iteratively making decisions based on gains and losses of tokens. When administered intramuscularly or intranasally, ketamine reduced the aversiveness of undesirable outcomes such as losses of tokens without significantly affecting the evaluation of gains, behavioral perseveration, motivation, and other cognitive aspects of learning such as temporal credit assignment and time scales of choice and outcome memory. Ketamine's potentially antidepressant effect was separable from other side effects such as fixation errors, which unlike outcome evaluation, was readily countered with strong motivation to avoid errors. We discuss how the acute effect of ketamine to reduce the initial impact of negative events could potentially mediate longer-term antidepressant effects through mitigating the cumulative effect of those events produced by slowly decaying memory, and how the disruption-resistant affective memory might pose challenges in treating depression. Our study also invites future investigations on ketamine's antidepressant action over diverse mood states and with affective events exerting their impacts at diverse time scales.

Therapeutic doses of ketamine acutely attenuate the aversive effect of losses during decision-making

The discovery of rapid-acting antidepressant, ketamine has opened a pathway to a new generation of treatments for depression, and inspired neuroscientific investigation based on a new perspective that non-adaptive changes in the intrinsic excitatory and inhibitory circuitry might underlie the pathophysiology of depression. Nevertheless, it still remains largely unknown how the hypothesized molecular and synaptic levels of changes in the circuitry might mediate behavioral and neuropsychological changes underlying depression, and how ketamine might restore adaptive behavior. Here, we used computational models to analyze behavioral changes induced by therapeutic doses of ketamine, while rhesus macaques were iteratively making decisions based on gains and losses of tokens. When administered intramuscularly or intranasally, ketamine reduced the aversiveness of undesirable outcomes such as losses of tokens without significantly affecting the evaluation of gains, behavioral perseveration, motivation, and other cognitive aspects of learning such as temporal credit assignment and time scales of choice and outcome memory. Ketamine’s potentially antidepressant effect was separable from other side effects such as fixation errors, which unlike outcome evaluation, was readily countered with strong motivation to avoid errors. We discuss how the acute effect of ketamine to reduce the initial impact of negative events could potentially mediate longer-term antidepressant effects through mitigating the cumulative effect of those events produced by slowly decaying memory, and how the disruption-resistant affective memory might pose challenges in treating depression. Our study also invites future investigations on ketamine’s antidepressant action over diverse mood states and with affective events exerting their impacts at diverse time scales.

Abstract PO2-02-07: Clinicopathological Features and Prognostic Role of HER2 Low in Early Breast Cancer: A real world study

Abstract Background: The definition of human epidermal growth factor receptor-2(HER2) low was proposed with the development of T-DXd, a novel antibody-drug conjugate (ADCs) targeting HER2 in the field of breast cancer (BC) treatments. However, whether HER2 low is a distinct subgroup is still an ongoing debate with mixed results. Current retrospective studies focused on HER2 low concentrated more on metastatic BC, less was known in early BC. The retrospective study was conducted based on HER2 low early BC to comprehensively analyze its clinicopathological features and prognostic roles compared with HER2 IHC0. Methods: This single institution retrospective study enrolled 999 early stage (stage I through III) HER2 negative invasive BC patients diagnosed at Chinese PLA General Hospital from January 2010 to December 2015. Tumors with HER2 immunohistochemical (IHC) score of 1+ or 2+ with negative in situ hybridization assay were defined as HER2 low. Clinicopathological characteristics s and survival outcomes including disease-free survival (DFS) and overall survival (OS) were compared between HER2 IHC0 and HER2 low groups. The correlations between HER2 expression and estrogen receptor (ER) status were determined by Mantel-Haenszel χ2 test. Cohen’s kappa coefficient (k) was adopted to evaluate the concordance between HER2 expression on primary tumors and matched biopsies. Results: 999 patients were eligible for inclusion criteria, among which the percentages of HER2 low in the whole cohort, HR positive group and HR negative group were 83.6%, 86.54%, 72.14% respectively. It was observed the presence of a significant higher proportion of ER level &amp;gt; 10% (p &amp;lt; 0.001), PgR positive (p &amp;lt; 0.001) and more patients who received endocrine therapy (p = 0.002). In HR positive group, clinicopathological features were balanced between HER2 IHC0 and HER2 low. In HR negative group, HER2 low manifested a higher proportion of invasive ductal type (p = 0.016) compared with HER2 IHC0. Survival analysis showed a significantly longer OS in HER2 low BC than HER2 IHC0. (HR: 0.458, 95%CI: 0.262-0.800, p = 0.0005). Nevertheless, the independent role was not reached in DFS. When stratified by HR status, patients with HER2 low in HR positive group demonstrated a longer OS than HER2 IHC0 (HR: 0.55, 95%CI: 0.273-1.105, p = 0.0385). The same trend was observed in HR negative group (HR: 0.385, 95%CI: 0.158-0.939, p = 0.0132). Neither the HR positive group nor the HR negative group achieved significant DFS. Besides, a positive correlation was observed between ER status and the rate of HER2 low (Mantel-Haenszel c2 test, p &amp;lt; 0.001, Pearson’s R = 0.159, P &amp;lt; 0.001). No regularity of survival differences between HER2 IHC0 and HER2 low was found in each ER level in the exploratory study. Finally, 119 patients who developed relapsed or metastatic disease were identified, with the most prevalent metastatic site being bone (31.1%), following by lung (16.80%) and lymph node (13.44%). Among 52 patients with matched biopsy samples, dynamic changes of HER2 IHC status were confirmed in both primary and relapsed statuses, with an discordance rate of 28.84% (K = 0.194, 95%CI: 0.168-0.219). conclusion: HER2 low expression breast cancer may not be regarded as a unique BC group in this real-world population due to similar clinicopathological features and prognostic roles especially in hormone-receptor positive cases. ER level was positively correlated with the rate of HER2 low population. Overall, whether HER2 low is a distinct subgroup remains to be supported and validated by more data both in clinical and molecular levels. Key words: HER2 low; Breast cancer; Clinicopathological Features; Prognosis; Molecular type Clinicopathological Features and Prognostic Role of HER2 Low in Early Breast Cancer: A real world study Citation Format: Ziqing Kong, Weihong Zhao. Clinicopathological Features and Prognostic Role of HER2 Low in Early Breast Cancer: A real world study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-02-07.

Coordination Confined Silver-Organic Framework for High Performance Electrochemical Deionization.

Silver (Ag) is deemed a promising anode material for capacitive deionization (CDI) due to its high theoretical capacity and efficient selectivity to Cl-. However, the strong volume change during the conversion reaction significantly undermines the cycling performance of the Ag electrode. Additionally, achieving well-dispersed Ag in the active matrix is challenging, as Ag electrodes prepared by conventional thermal reduction tend to agglomerate. Herein, the organic linker confinement strategy is proposed, applying metal-organic framework (MOF) chemistry between Ag nodes and organic ligands to construct Ag-based MOF. The uniform dispersion of Ag at the molecular level, confined in the organic matrix, efficiently enhances the utilization of active sites, and strengthens the interfacial stability of Ag. Consequently, the Ag-MOF for the CDI anode exhibits an excellent Cl- removal capacity of 121.52mg g-1 at 20mA g-1 in 500mg L-1 NaCl solution, and a high Ag utilization rate of 60.54%. After 100 cycles, a capacity retention of 96.93% is achieved. Furthermore, the Cl- capture mechanism of Ag-MOF is elucidated through density functional theory (DFT) calculations, ex situ XRD, ex situ Raman and XPS. This ingenious electrode design can offer valuable insights for the development of high-performance conversion electrodes for CDI applications.

Investigations on Growth, Characterization, NCI-RDG, AIM, Molecular Docking and In-Silico ADME Properties of 1,2-Benzene Dicarboxylic Acid Anhydride

Superior single crystal of 1,2-benzene dicarboxylic acid anhydride additionally called Phthalic anhydride (PAN) was developed via solution growth at low temperatures. Single crystal X-ray diffraction investigation revealed the crystal system and unit cell characteristics. The phase stability and crystalline nature were uncovered by powder X-ray diffraction analysis. FT-IR examination was done for the titular material so as to survey the various functional groups. With the use of the VEDA program's relevant resources, vibrational assignments have been made on the concept of Potential Energy Distribution (PED). Density Functional Theory (DFT) was employed to smooth out the molecular structure of PAN and was additionally utilized to consider FT-IR spectrum at molecular level. Non covalent interactions reduced density gradient (NCI-RDG) analysis has been used for the prediction of the weak interaction in the actual space in terms of the electron density along with its derivatives for PAN. Atoms in Molecules (AIM) analysis was carried for out for PAN. The docking research of the small molecule (PAN) with target protein confirmed that this is a great molecule which docks nicely with numerous targets associated with Hypoxia Inducible Factor 1-α. The absorption, distribution, metabolism, excretion (ADME) characteristics have been calculated with the assist of online server preADMET.