Repopulating Microglia Promote Brain Repair in an IL-6-Dependent Manner.

Cognitive dysfunction and reactive microglia are hallmarks of traumatic brain injury (TBI), yet whether these cells contribute to cognitive deficits and secondary inflammatory pathology remains poorly understood. Here, we show that removal of microglia from the mouse brain has little effect on the outcome of TBI, but inducing the turnover of these cells through either pharmacologic or genetic approaches can yield a neuroprotective microglial phenotype that profoundly aids recovery. The beneficial effects of these repopulating microglia are critically dependent on interleukin-6 (IL-6) trans-signaling via the soluble IL-6 receptor (IL-6R) and robustly support adult neurogenesis, specifically by augmenting the survival of newborn neurons that directly support cognitive function. We conclude that microglia in the mammalian brain can be manipulated to adopt a neuroprotective and pro-regenerative phenotype that can aid repair and alleviate the cognitive deficits arising from brain injury.

Ethylene Polymerizations Catalyzed by Fluorinated "Sandwich" Diimine-Nickel and Palladium Complexes.

Nickel and palladium complexes bearing "sandwich" diimine ligands with perfluorinated aryl caps have been synthesized, characterized, and explored in ethylene polymerization reactions. The X-ray crystallographic analysis of the precatalysts 16 and 6b shows differences from their nonfluorinated analogues 17 and 19, with the perfluorinated aryl caps centered precisely over the nickel and palladium centers, which results in higher buried volumes of the metal centers relative to the nonfluorinated analogues. The sandwich diimine-palladium complexes 5a and 5b containing perfluorinated aryl caps polymerize ethylene in a controlled fashion with activities that are substantially increased compared with their nonfluorinated analogues. Migratory insertion rates in relevant methyl ethylene complexes agree with the activities exhibited in bulk polymerization experiments. DFT studies suggest that facility of ethylene rotation from its preferred orientation perpendicular to the Pd-alkyl bond into a parallel in-plane conformation contributes to the higher polymerization activity for 5b relative to 18a. For these palladium systems, polymer molecular weights can be controlled via hydrogen addition (hydrogenolysis), which is unusual for late-transition-metal-catalyzed olefin polymerizations with no catalyst deactivation occurring. Sandwich diimine-nickel complexes 6a and 6b with perfluorinated aryl caps show ethylene polymerization activities that are about half of those of classical tetraisopropyl-substituted catalyst 2 but again are more active than the analogous nonfluorinated sandwich complexes. Ethylene polymerizations exhibit living behavior, and branched ultrahigh-molecular-weight polyethylenes (UHMWPEs) with very low-molecular-weight distributions (less than 1.1) are obtained. The activated nickel catalysts are stable in the absence of monomer and show good long-term stability at 25 °C.

Trajectory of Healthcare Contact Days for Veterans With Advanced Gastrointestinal Malignancy.

How and where patients with advanced cancer facing limited survival spend their time is critical. Healthcare contact days (days with healthcare contact outside the home) offer a patient-centered and practical measure of how much of a person's life is consumed by healthcare. We retrospectively analyzed contact days among decedent veterans with stage IV gastrointestinal cancer at the Minneapolis Veterans Affairs Healthcare System from 2010 to 2021. Among 468 decedents, the median overall survival was 4 months. Patients spent 1 in 3 days with healthcare contact. Over the course of illness, the percentage of contact days followed a "U-shaped" pattern, with an initial post-diagnosis peak, a lower middle trough, and an eventual rise as patients neared the end-of-life. Contact days varied by clinical factors and by sociodemographics. These data have important implications for improving care delivery, such as through care coordination and communicating expected burdens to and supporting patients and care partners.

Single-cell RNA sequencing reveals peripheral blood leukocyte responses to spinal cord injury in mice with humanised immune systems.

Next-generation humanised mouse models and single-cell RNA sequencing (scRNAseq) approaches enable in-depth studies into human immune cell biology. Here we used NSG-SGM3 mice engrafted with human umbilical cord haematopoietic stem cells to investigate how human immune cells respond to and/or are changed by traumatic spinal cord injury (SCI). We hypothesised that the use of such mice could help advance our understanding of spinal cord injury-induced immune depression syndrome (SCI-IDS), and also how human leukocytes change as they migrate from the circulation into the lesion site. Our scRNAseq experiments, supplemented by flow cytometry, demonstrate the existence of up to 11 human immune cell (sub-) types and/or states across the blood and injured spinal cord (7 days post-SCI) of humanised NSG-SGM3 mice. Further comparisons of human immune cell transcriptomes between naïve, sham-operated and SCI mice identified a total of 579 differentially expressed genes, 190 of which were 'SCI-specific' (that is, genes regulated only in response to SCI but not sham surgery). Gene ontology analysis showed a prominent downregulation of immune cell function under SCI conditions, including for T cell receptor signalling and antigen presentation, confirming the presence of SCI-IDS and the transcriptional signature of human leukocytes in association with this phenomenon. We also highlight the activating influence of the local spinal cord lesion microenvironment by comparing the transcriptomes of circulating versus infiltrated human immune cells; those isolated from the lesion site were enriched for genes relating to both immune cell activity and function (e.g., oxidative phosphorylation, T cell proliferation and antigen presentation). We lastly applied an integrated bioinformatics approach to determine where immune responses in humanised NSG-SGM3 mice appear congruent to the native responses of human SCI patients, and where they diverge. Collectively, our study provides a valuable resource and methodological framework for the use of these mice in translational research.

Predicting subsolid pulmonary nodules before percutaneous needle biopsy: a comparison of artificial neural network and biopsy results.

AIM: To establish an artificial neural network (ANN) model to predict subsolid nodules (SSNs) before percutaneous core-needle biopsy (PCNB). The results of the two methods were compared to provide guidance on the treatment of SSNs. MATERIALS AND METHODS: This was a single-centre retrospective study using data from 1,459 SSNs between 2013 and 2021. The ANN was developed using data from patients who underwent surgery following computed tomography (CT) (SFC) and validated using data from patients who underwent surgery following biopsy (SFB). The prediction results of the ANN for the PCNB group and the histopathological results obtained after biopsy were compared with the histopathological results of lung nodules in the same group after surgery. Additionally, the choice of predictors for PCNB was analysed using multivariate analysis. RESULTS: There was no significant difference between the accuracies of the ANN and PCNB in the SFB group (p=0.086). The sensitivity of PCNB was lower than that of the ANN (p=0.000), but the specificity was higher (p=0.001). PCNB had better diagnostic ability than the ANN. The incidence of precursor lesions and non-neoplastic lesions in the SFB group was lower than that in the SFC group (p=0.000). A history of malignant tumours, size (2-3 cm), volume (>400 cm3) and mean CT value (≥-450 HU) are important factors for selecting PCNB. CONCLUSIONS: Both ANN and PCNB have comparable accuracy in diagnosing SSNs; however, PCNB has a slightly higher diagnostic ability than ANN. Selecting appropriate patients for PCNB is important for maximising the benefit to SSN patients.

Significant Vision Recovery from Filler-Induced Complete Blindness with Combined Intra-Arterial Injection of Hyaluronidase and Thrombolytic Agents.

With the increase of cosmetic injectable hyaluronic acid (HA), there have been more cases with serious complications, including skin necrosis, blindness, and cerebral embolism. Patients who have recovered from HA filler-induced total vision loss are extremely rare. We report a case of a 27-year-old female who developed severe ocular pain on the right side and total vision loss following a 1.0 ml HA filler injection in the nasal dorsum. She arrived at our hospital 4 hours later. Her visual acuity was no light perception (NLP), and she exhibited eyelid ptosis, ophthalmoplegia, and frontal and nasal ecchymosis. She was promptly treated with subcutaneous and retrobulbar hyaluronidase injections, as well as intra-arterial 1500 IU hyaluronidase injections into the right ophthalmic artery with DSA assistance. Her vision improved from NLP to counting fingers at 1.0 meters. Unfortunately, 13 hours later, she felt an intense headache, and her vision again decreased to NLP. We immediately performed an injection of 1500 IU hyaluronidase combined with 8 mg alteplase for intra-arterial thrombolysis (IAT) into the right ophthalmic artery. Her vision improved immediately afterward. After 3 months, her visual acuity had significantly recovered from NLP (admission vision status) to 20/50 (Snellen chart with glasses). Similarly, skin, conjunctival, eye movement, and ptosis symptoms completely recovered. This case demonstrates that reversal of complete blindness due to embolism of the ophthalmic and central retinal arteries could be accomplished through multidisciplinary therapies, especially IAT using fibrinolytic agents combined with hyaluronidase followed by an anticoagulant regimen.Level of evidence VThis journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine Ratings, please refer to Table of Contents or online Instructions to Authors www.springer.com/00266 .

[Inhibition connexin 43 by mimetic peptide Gap27 mediates protective effects on 6-hydroxydopamine induced Parkinson's disease mouse model].

OBJECTIVE: To explore whether the using of mimetic peptide Gap27, a selective inhibitor of connexin 43 (Cx43), could block the death of dopamine neurons and influence the expression of Cx43 in 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease mouse models. METHODS: Eighteen C57BL/6 mice were randomly divided into control group, 6-OHDA group and 6-OHDA+Gap27 group, with 6 mice in each group. Bilateral substantia nigra stereotactic injection was performed. The control group was injected with ascorbate solution, 6-OHDA group was injected with 6-OHDA solution, and 6-OHDA+Gap27 group was injected with 6-OHDA and Gap27 mixed solution. Immuno-histochemical staining was used to detect the number of dopamine neurons, quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of Cx43 messenger ribonucleic acid (mRNA), immuno-fluorescence staining was used to detect the distribution of Cx43 protein, the contents of Cx43 protein and Cx43 phosphorylation at serine 368 (Cx43-ps368) in mouse midbrain were detected by Western blot. RESULTS: After injection of 6-OHDA, numerous dopamine neurons in substantia nigra died as Cx43 content increased, Cx43-ps368 content decreased. Mixing Gap27 while injecting 6-OHDA could reduce the number of death dopamine neurons and weaken the changes of Cx43 and Cx43-ps368 content caused by 6-OHDA. The number of tyrosine hydroxylase (TH) immunoreactive positive neurons in 6-OHDA group decreased to 27.7% ± 0.02% of the control group (P < 0.01); The number of TH immunoreactive positive neurons in 6-OHDA+Gap27 group was (1.64±0.16) times higher than that in 6-OHDA group (P < 0.05); The content of total Cx43 protein in 6-OHDA group was (1.44±0.07) times higher than that in 6-OHDA+Gap27 group (P < 0.05) while (1.68±0.07) times higher than that in control group (P < 0.01). In 6-OHDA group, the content of Cx43-ps368 protein and its proportion in total Cx43 protein were significantly lower than that in 6-OHDA+Gap27 group (P < 0.05). CONCLUSION: In 6-OHDA mouse models, mimetic peptide Gap27 played a protective role in reducing the damage to substantia nigra dopamine neurons, which was induced by 6-OHDA. The overexpression of Cx43 protein might have neurotoxicity to dopamine neuron. Meanwhile, decreasing Cx43 protein level and keeping Cx43-ps368 protein level may be the protective mechanisms of Gap27.

Single-cell RNA-seq of human induced pluripotent stem cells reveals cellular heterogeneity and cell state transitions between subpopulations.

Heterogeneity of cell states represented in pluripotent cultures has not been described at the transcriptional level. Since gene expression is highly heterogeneous between cells, single-cell RNA sequencing can be used to identify how individual pluripotent cells function. Here, we present results from the analysis of single-cell RNA sequencing data from 18,787 individual WTC-CRISPRi human induced pluripotent stem cells. We developed an unsupervised clustering method and, through this, identified four subpopulations distinguishable on the basis of their pluripotent state, including a core pluripotent population (48.3%), proliferative (47.8%), early primed for differentiation (2.8%), and late primed for differentiation (1.1%). For each subpopulation, we were able to identify the genes and pathways that define differences in pluripotent cell states. Our method identified four transcriptionally distinct predictor gene sets composed of 165 unique genes that denote the specific pluripotency states; using these sets, we developed a multigenic machine learning prediction method to accurately classify single cells into each of the subpopulations. Compared against a set of established pluripotency markers, our method increases prediction accuracy by 10%, specificity by 20%, and explains a substantially larger proportion of deviance (up to threefold) from the prediction model. Finally, we developed an innovative method to predict cells transitioning between subpopulations and support our conclusions with results from two orthogonal pseudotime trajectory methods.

Genome-wide analysis of SARS-CoV-2 strains circulating in Vietnam: Understanding the nature of the epidemic and role of the D614G mutation.

Genome-wide analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains is essential to better understand infectivity and virulence and to track coronavirus disease 2019 (COVID-19) cases and outbreaks. We performed whole-genome sequencing of 27 SARS-CoV-2 strains isolated between January 2020 and April 2020. A total of 54 mutations in different genomic regions was found. The D614G mutation, first detected in March 2020, was identified in 18 strains and was more likely associated with a lower cycle threshold (<25) in real-time reverse-transcription polymerase chain reaction diagnostic tests than the original D614 (prevalence ratio = 2.75; 95% confidence interval, 1.19-6.38). The integration of sequencing and epidemiological data suggests that SARS-CoV-2 transmission in both quarantine areas and in the community in Vietnam occur at the beginning of the epidemic although the country implemented strict quarantine quite early, with strict contact tracing, and testing. These findings provide insights into the nature of the epidemic, as well as shape strategies for COVID-19 prevention and control in Vietnam.

Survival after out-of-hospital cardiac arrest, Viet Nam: multicentre prospective cohort study.

OBJECTIVE: To investigate factors associated with survival after out-of-hospital cardiac arrest in Viet Nam. METHODS: We did a multicentre prospective observational study of people (> 18 years) presenting with out-of-hospital cardiac arrest (not caused by trauma) to three tertiary hospitals in Viet Nam from February 2014 to December 2018. We collected data on characteristics, management and outcomes of patients with out-of-hospital cardiac arrest and compared these data by type of transportation to hospital and survival to hospital admission. We assessed factors associated with survival to admission to and discharge from hospital using logistic regression analysis. FINDINGS: Of 590 eligible people with out-of-hospital cardiac arrest, 440 (74.6%) were male and the mean age was 56.1 years (standard deviation: 17.2). Only 24.2% (143/590) of these people survived to hospital admission and 14.1% (83/590) survived to hospital discharge. Most cardiac arrests (67.8%; 400/590) occurred at home, 79.4% (444/559) were witnessed by bystanders and 22.3% (124/555) were given cardiopulmonary resuscitation by a bystander. Only 8.6% (51/590) of the people were taken to hospital by the emergency medical services and 32.2% (49/152) received pre-hospital defibrillation. Pre-hospital defibrillation (odds ratio, OR: 3.90; 95% confidence interval, CI: 1.54-9.90) and return of spontaneous circulation in the emergency department (OR: 2.89; 95% CI: 1.03-8.12) were associated with survival to hospital admission. Hypothermia therapy during post-resuscitation care was associated with survival to discharge (OR: 5.44; 95% CI: 2.33-12.74). CONCLUSION: Improvements are needed in the emergency medical services in Viet Nam such as increasing bystander cardiopulmonary resuscitation and public access defibrillation, and improving ambulance and post-resuscitation care.

New Neutral Nickel and Palladium Sandwich Catalysts: Synthesis of Ultra-High Molecular Weight Polyethylene (UHMWPE) via Highly Controlled Polymerization and Mechanistic Studies of Chain Propagation.

New neutral nickel and palladium ethylene polymerization catalysts have been prepared that incorporate an anionic (N,O) chelating ligand. Extensive axial shielding is provided by two 3,5-dichloroaryl moieties in a "sandwich" orientation. Such shielding results in an exceptionally slow rate of chain transfer relative to migratory insertion in the nickel catalyst, and thus highly controlled polymerization of ethylene is observed, leading to lightly branched ultra-high molecular weight polyethylene with Mn values up to 4.1 × 106 g/mol. The analogous palladium catalysts provide the means for a detailed mechanistic study of chain propagation in an electronically asymmetric neutral palladium catalyst. Both isomers of the methyl ethylene complex can be generated and observed at low temperatures allowing experimental elucidation of mechanistic details of chain propagation probed in other electronically asymmetric systems only through DFT studies or by examination of model studies. The barrier to migratory insertion in these complexes is ca. 19.2 kcal/mol. Investigation of the equilibration of the methyl ethylene isomers in the presence of excess ethylene showed the isomerization rate is dependent on ethylene concentration. This is the first direct proof that isomerization in these alkyl ethylene intermediates is catalyzed by ethylene. Furthermore, isomer equilibration is much faster than migratory insertion so that the barriers for insertion of individual isomers cannot be determined.

Clinical features, isolation, and complete genome sequence of severe acute respiratory syndrome coronavirus 2 from the first two patients in Vietnam.

In January 2020, we identified two severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients in a familial cluster with one person coming from Wuhan, China. The complete genome sequences of two SARS-CoV-2 strains isolated from these patients were identical and 99.98% similar to strains isolated in Wuhan. This is genetically suggestive of human-to-human transmission of SARS-CoV-2 and indicates Wuhan as the most plausible origin of the early outbreak in Vietnam. The younger patient had a mild upper respiratory illness and a brief viral shedding, whereas the elderly with multi-morbidity had pneumonia, prolonged viral shedding, and residual lung damage. The evidence of nonsynonymous substitutions in the ORF1ab region of the viral sequence warrants further studies.

Nonequilibrium Green's Function's Approach to the Calculation of Work Statistics.

The calculation of work distributions in a quantum many-body system is of significant importance and also of formidable difficulty in the field of nonequilibrium quantum statistical mechanics. To solve this problem, inspired by the Schwinger-Keldysh formalism, we propose the contour-integral formulation for work statistics. Based on this contour integral, we show how to do the perturbation expansion of the characteristic function of work (CFW) and obtain the approximate expression of the CFW to the second order of the work parameter for an arbitrary system under a perturbative protocol. We also demonstrate the validity of fluctuation theorems by utilizing the Kubo-Martin-Schwinger condition. Finally, we use noninteracting identical particles in a forced harmonic potential as an example to demonstrate the powerfulness of our approach.

Work Statistics across a Quantum Phase Transition.

We investigate the statistics of the work performed during a quench across a quantum phase transition using the adiabatic perturbation theory when the system is characterized by independent quasiparticles and the "single-excitation" approximation is assumed. It is shown that all the cumulants of work exhibit universal scaling behavior analogous to the Kibble-Zurek scaling for the average density of defects. Two kinds of transformations are considered: quenches between two gapped phases in which a critical point is traversed, and quenches that end near the critical point. In contrast to the scaling behavior of the density of defects, the scaling behavior of the cumulants of work are shown to be qualitatively different for these two kinds of quenches. However, in both cases the corresponding exponents are fully determined by the dimension of the system and the critical exponents of the transition, as in the traditional Kibble-Zurek mechanism (KZM). Thus, our study deepens our understanding about the nonequilibrium dynamics of a quantum phase transition by revealing the imprint of the KZM on the work statistics.

[Effect of benzo(a)pyrene on dopaminergic neurons and α-synuclein in brain and its mechanism involved].

OBJECTIVE: To analyze the effect of benzopyrene on the decrease of dopaminergic neurons, and the increase and aggregation of α-synuclein, which are the pathological features of Parkinson's disease, and to explore its possible mechanisms. METHODS: Eight-month-old transgenic mice with human SNCA gene were randomly divided into a BaP-exposed group and a control group. BaP and solvent corn oil were injected intraperitoneally to BaP-exposed group and control group respectively, once a day for 60 days. The motor dysfunction of mice was tested by rotarod test. The effects of BaP on the decrease of dopaminergic neurons and increase and aggregation of α-synuclein were observed by immunohistochemistry and Western blot experiments respectively, and the expression of related mRNA was detected by quantitative real-time PCR (qRT-PCR). Twenty genes were tested in the study, mainly related to neurotransmitter transporter (2 genes), neurotransmitter receptor function (10 genes), cellular autophagy (5 genes), and α-synuclein aggregation and degradation (3 genes). RESULTS: After BaP exposure, the movement time of the mice in the rotarod test was significantly reduced (P<0.05). The substantia nigra dopami-nergic neurons in the mice were significantly reduced, which was 62% of the control group (P<0.05), and the expression of α-synuclein in the midbrain increased, which was 1.36 times that of the control group (P<0.05). After BaP exposure, mRNA expressions of 14 genes in the midbrain of the mice were significantly down-regulated (P<0.05). Alpha-synuclein degradation and cell autophagy (5 genes), neuron transporters (2 genes), and neurotransmitter receptor functions (5 genes) were involved. The expression of one gene, Synphilin-1, was significantly up-regulated (P<0.01), which was related to α-synuclein aggregation. CONCLUSION: BaP exposure not only inhibited function of neurotransmitter receptor and dopamine transporter, but also interfered cell autophagy, thereby hindering the degradation of α-synuclein, which could lead to decrease of dopaminergic neurons in substantia nigra and increase and aggregation of α-synuclein in midbrain, as the significant pathology of Parkinson's disease. Therefore, BaP exposure may increase the risk of Parkinson's disease.

Willing to Work But Not to Wait: Individuals with Greater Alcohol Use Disorder Show Increased Delay Discounting Across Commodities and Less Effort Discounting for Alcohol.

BACKGROUND: Delay discounting refers to the devaluation of a reward given increasing delays to delivery. Similarly, effort discounting refers to the devaluation of a reward given increasing effort required to obtain it. Individuals with substance use disorder show higher rates of delay discounting, exacerbating short-term positive reinforcement at the expense of long-term consequences. This study explores how effort discounting compares to delay discounting behavior among alcohol users as well as how these preferences change between monetary and alcohol rewards. METHODS: A total of 100 participants completed an online survey through Amazon Mechanical Turk. Participant alcohol use was evaluated using DSM-5 and the Alcohol Use Disorders Identification Test criteria. All participants completed 4 randomized discounting tasks involving delay or effort discounting, in which the reward was money or alcohol. A follow-up experiment (n = 423) added the alcohol purchase task to assess alcohol valuation. RESULTS: Individuals with greater alcohol use disorder (AUD) severity discounted future money and alcohol significantly more than those with less AUD. However, individuals meeting more DSM-5 criteria were only willing to perform more effort for alcohol. The follow-up experiment replicated these findings and demonstrated that individuals with greater AUD also showed an increased valuation of alcohol and alcohol value-mediated effort discounting. CONCLUSIONS: These results suggest that individuals with greater AUD were less willing to wait for money or alcohol. While all participants were willing to work for money regardless of AUD severity, individuals with greater AUD showed increased valuation of alcohol drinks and were willing to exert more effort to obtain alcohol. Together, these results paint a picture of individuals with increased AUD as both more impulsive and willing to work to obtain alcohol, contributing to our understanding of decision making among individuals who abuse substances.

Effects of triethylene glycol dimethacrylate and hydroxyethyl methacrylate on macrophage polarization.

AIM: To evaluate the effects of hydrophilic dental resin monomers, triethylene glycol dimethacrylate (TEGDMA) and hydroxyethyl methacrylate (HEMA), on the polarization of a human monocyte cell line (THP-1). METHODOLOGY: THP-1 cells were treated with resin monomers at noncytotoxic concentrations for 48 h and were analysed for CD86 and CD206 expressions using flow cytometry. The cells were stimulated for polarization in the presence of resin monomers (co-treatment) or after treatment with monomers (pre-treatment). CD86 and CD206 mRNA in co-treated cells was evaluated using quantitative real-time polymerase chain reaction. The release of TNF-α and TGF-ß by pre-treated and co-treated cells was assessed using enzyme-linked immunosorbent assay. Morphological changes of macrophages during polarization were observed using bright-field microscopy. One-way analysis of variance was used for statistical analysis. RESULTS: TEGDMA (1 mmol L-1 ) and HEMA (2 mmol L-1 ) did not induce CD86 and CD206 expressions in THP-1 cells but rather inhibited their expressions in the co-treated cells. The inhibitory effects also appeared at the transcription level. However, the expression of surface markers was not affected by pre-treatment with resin monomers. The release of TNF-α and TGF-ß by M1- and M2-stimulated cells, respectively, was suppressed by co-treatment (P < 0.05). Microscopic studies revealed that co-treatment with resin monomers suppressed polarization-associated morphological changes such as cell volume increase. CONCLUSIONS: TEGDMA and HEMA inhibited macrophage polarization to both M1 and M2 at the transcription level, and the inhibitory effects disappeared upon the removal of resin monomers from the cell culture.

Path Integral Approach to Quantum Thermodynamics.

Work belongs to the most basic notions in thermodynamics but it is not well understood in quantum systems, especially in open quantum systems. By introducing a novel concept of the work functional along an individual Feynman path, we invent a new approach to study thermodynamics in the quantum regime. Using the work functional, we derive a path integral expression for the work statistics. By performing the ℏ expansion, we analytically prove the quantum-classical correspondence of the work statistics. In addition, we obtain the quantum correction to the classical fluctuating work. We can also apply this approach to an open quantum system in the strong coupling regime described by the quantum Brownian motion model. This approach provides an effective way to calculate the work in open quantum systems by utilizing various path integral techniques. As an example, we calculate the work statistics for a dragged harmonic oscillator in both isolated and open quantum systems.

Experimental Test of the Differential Fluctuation Theorem and a Generalized Jarzynski Equality for Arbitrary Initial States.

Nonequilibrium processes of small systems such as molecular machines are ubiquitous in biology, chemistry, and physics but are often challenging to comprehend. In the past two decades, several exact thermodynamic relations of nonequilibrium processes, collectively known as fluctuation theorems, have been discovered and provided critical insights. These fluctuation theorems are generalizations of the second law and can be unified by a differential fluctuation theorem. Here we perform the first experimental test of the differential fluctuation theorem using an optically levitated nanosphere in both underdamped and overdamped regimes and in both spatial and velocity spaces. We also test several theorems that can be obtained from it directly, including a generalized Jarzynski equality that is valid for arbitrary initial states, and the Hummer-Szabo relation. Our study experimentally verifies these fundamental theorems and initiates the experimental study of stochastic energetics with the instantaneous velocity measurement.