Performance of polar coded probabilistic shaped PAM8 with systematic interleaver and identically distributed pilot in weak turbulence.

In this paper, for the first time to the best of our knowledge, we investigate the experiment of polar coded probabilistic shaped 8-ary pulse amplitude modulation (PS-PAM8) in weak turbulence. A systematic interleaver (SIL) is proposed to improve the polar code performance for PS-PAM8, compatible with the 5 G channel coding standard. Considering the effects of turbulence and shaped constellations, the pilot with identical distributions as the transmitted data is used for dynamic channel estimation to avoid demodulation failure. Moreover, the application of hybrid equalization with nonlinear and linear equalizers effectively reduces the receiver sensitivity. In 25 GBd transmission over a 4 m free-space link, the transmission performance of polar coded PAM8 schemes with SIL is better than that of the low-density parity check code by 1.0 dB, and the power budget is further saved by 0.72∼0.83 dB after linear equalization. Meanwhile, the shaping gains of polar coded PS-PAM8 with SIL and hybrid equalization are up to 2.0 dB at 1.5 bits/channel use. In addition, different weak turbulence conditions can be generated inside a chamber, and the observed channel fading is consistent with the log-normal model. The results show that the proposed polar coded PS scheme can improve the Q-factor by 0.49∼1.74 dB in different turbulence conditions.

Modeling facial perception in group context from a serial perception perspective.

By utilizing statistical properties and summary statistics, the visual system can efficiently integrate perception of spatially and temporally adjacent stimuli into perception of a given target. For instance, perception of a target face can either be biased positively toward previous faces (e.g. the serial dependence effect) or be biased negatively by surrounding faces in the same trial/space (e.g. spatial ensemble averaging). However, both aspects were investigated separately. As spatial and temporal processing share the same purpose to reduce redundancy in visual processing, if one statistical processing occurs, would the statistical processing in the other domain still exist or be discarded? We investigated this question by exploring whether serial dependence of face perception (of attractiveness and averageness) survives when the changed face perception in the group context occurs. The results of Markov Chain modeling and conventional methods suggested that serial dependence (the temporal aspect) co-occurs with changed face perception in the group context (the spatial aspect). We also utilized the Hidden Markov modeling, as a new mathematical method, to model statistical processing from both domains. The results confirmed the co-occurrence of temporal effect and changed face perception in the group context for both attractiveness and averageness, suggesting potentially different spatial and temporal compression mechanisms in high-level vision. Further modeling and cluster analysis further revealed that the detailed computation of spatially and temporally adjacent faces in the attractiveness and averageness processing were similar yet different among different individuals. This work builds a bridge to understanding mathematical principles underlying changed face perception in the group context from the serial perspective.

Antibiotic resistome and its association with bacterial communities during sewage sludge composting.

Composting is widely used for recycling of urban sewage sludge to improve soil properties, which represents a potential pathway of spreading antibiotic resistant bacteria and genes to soils. However, the dynamics of antibiotic resistance genes (ARGs) and the underlying mechanisms during sewage sludge composting were not fully explored. Here, we used high-throughput quantitative PCR and 16S rRNA gene based illumina sequencing to investigate the dynamics of ARGs and bacterial communities during a lab-scale in-vessel composting of sewage sludge. A total of 156 unique ARGs and mobile genetic elements (MGEs) were detected encoding resistance to almost all major classes of antibiotics. ARGs were detected with significantly increased abundance and diversity, and distinct patterns, and were enriched during composting. Marked shifts in bacterial community structures and compositions were observed during composting, with Actinobacteria being the dominant phylum at the late phase of composting. The large proportion of Actinobacteria may partially explain the increase of ARGs during composting. ARGs patterns were significantly correlated with bacterial community structures, suggesting that the dynamic of ARGs was strongly affected by bacterial phylogenetic compositions during composting. These results imply that direct application of sewage sludge compost on field may lead to the spread of abundant ARGs in soils.

Recent advances in application of computer-aided drug design in anti-COVID-19 Virials Drug Discovery.

Corona Virus Disease 2019 (COVID-19) is a global pandemic epidemic caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which poses a serious threat to human health worldwide and results in significant economic losses. With the continuous emergence of new virus strains, small molecule drugs remain the most effective treatment for COVID-19. The traditional drug development process usually requires several years; however, the development of computer-aided drug design (CADD) offers the opportunity to develop innovative drugs quickly and efficiently. The literature review describes the general process of CADD, the viral proteins that play essential roles in the life cycle of SARS-CoV-2 and can serve as therapeutic targets, and examples of drug screening of viral target proteins by applying CADD methods. Finally, the potential of CADD in COVID-19 therapy, the deficiency, and the possible future development direction are discussed.

Acute liver failure as initial presentation in a Chinese patient with Budd-Chiari syndrome due to protein C deficiency: A case report and literature review.

Acute liver failure is an uncommon presentation in the clinic. Common causes for acute liver failure include viral hepatitis and drug-related hepatotoxicity. However, acute liver failure due to Budd-Chiari syndrome is rare. This case highlights the importance of necessary constrast-enhanced imaging studies to rule out vascular etiologies of acute liver failure, in addition to common causes like viral or drug-induced hepatic failure. We present a case of a male Chinese patient who presented with nausea, vomiting, fatigue, and fever after eating a large amount of fatty food. Six days after hospitalization, the patient developed acute liver failure and hepatic encephalopathy. Contrast-enhanced computerized tomography and ultrasound examinations revealed thromboses in the hepatic veins and inferior vena cava. Further testing also showed decreased protein C activity. Therefore, a diagnosis of Budd-Chiari syndrome secondary to protein C deficiency was made. He received supportive care and a transjugular intrahepatic portal shunt. Hepatic function, coagulation panel results, and clinical presentations gradually returned to normal. Budd-Chiari syndrome from protein C deficiency could be a rare but valid cause of acute liver failure in Chinese patients.

Multiorgan dysfunction syndrome due to high-dose cantharidin poisoning: A case report.

BACKGROUND: This report delves into the diagnostic and therapeutic journey undertaken by a patient with high-dose cantharidin poisoning and multiorgan dysfunction syndrome (MODS). Particular emphasis is placed on the comprehensive elucidation of the clinical manifestations of high-dose cantharidin poisoning, the intricate path to diagnosis, and the exploration of potential underlying mechanisms. CASE SUMMARY: A patient taking 10 g of cantharidin powder orally subsequently developed MODS. The patient was treated with supportive care, fluid hydration and antibiotics, and hemoperfusion and hemofiltration therapy for 24 h and successfully recovered 8 d after hospital admission. Cantharidin poisoning can cause life-threatening MODS and is rare clinically. This case underscores the challenge in diagnosis and highlights the need for early clinical differentiation to facilitate accurate assessment and prompt intervention. CONCLUSION: This article has reported and analyzed the clinical data, diagnosis, treatment, and prognosis of a case of high-dose cantharidin poisoning resulting in MODS and reviewed the relevant literature to improve the clinical understanding of this rare condition.

Food-borne botulism from homemade sauce leading to cardiac arrest: A family case series with literature review.

Food-borne botulism is a rare but potentially fatal illness. Its management depends on rapid diagnosis and prompt antitoxin administration. However, diagnosing food-borne botulism can be challenging at an early stage. Here, we report a 62-year-old male with food-borne botulism. The patient presented with extremity muscle weakness, dyspnea, bilateral droopy eyelids (more significant on the right side), dysarthria, and progressive dysphagia. The electromyography indicated presynaptic membrane abnormalities. The toxicology screen reported a positive result for botulinum toxin type A. He received plasma exchange, botulism antitoxin, and supportive care. However, he had a cardiac arrest six days later. Spontaneous circulation was restored after immediate cardiopulmonary resuscitation. The patient gradually recovered his muscle strength and could have complete eyelid elevation. A detailed interview revealed that six family members developed similar symptoms. All of them consumed a homemade sauce prepared three years ago. They all tested positive for botulinum toxin type A. Two of them had cardiac arrests. Therefore, family aggregation could happen to botulism. Careful interviews, early diagnosis, and timely administration of botulism antitoxin are the keys to saving lives. Special attentions should be given to the cardiac evaluations since botulism can cause cardiac arrest and death.

Effects of Baduanjin exercise on quality-of-life and exercise capacity in patients with heart failure: A systematic review and meta-analysis.

PURPOSE: Exercise training is an efficient non-pharmacological intervention for patients with heart failure (HF). This study aimed to objectively evaluate the effects of Baduanjin exercise on the quality of life (QOL) and exercise capacity in patients with HF. METHODS: PubMed, Embase, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), and Wanfang data were searched from the date of their inception until 30 September 2022. All randomised controlled trials (RCTs) evaluating the effects of Baduanjin exercise on QOL and exercise capacity in patients with HF were selected. The primary outcomes were QOL, assessed using the Minnesota Living with Heart Failure Questionnaire (MLHFQ), and exercise capacity, evaluated using the 6-min walking test (6-MWT). A meta-analysis was performed by comparing the MLHFQ domain scores. Review Manager 5.3 and Stata 14.0, were used for the data analysis. RESULTS: Baduanjin exercise showed a favourable improvement of the overall QOL (mean difference = -8.25; 95% confidence interval: -13.62 to -2.89; P = 0.003) and exercise capacity (mean difference = 118.49; 95% confidence interval: 52.57 to 184.41; P = 0.0004). Meta-analyses of the MLHFQ domain score indicated that Baduanjin exercise significantly improved the patients' physical (mean difference = -2.83; 95% confidence interval: -3.76, -1.90; P < 0.00001), emotional (mean difference = -2.52; 95% confidence interval: -3.67 to -1.37; P < 0.0001), and general QOL (mean difference = -2.61; 95% confidence interval: -5.17 to -0.06; P = 0.05), based on the decrease in the MLHFQ domain score. Marked statistical heterogeneity (I2> 70%) was observed for all the QOL and exercise capacity outcomes. CONCLUSIONS: Baduanjin exercise is a safe, feasible, and acceptable intervention that can improve the QOL and exercise capacity in patients with HF. However, more RCTs with rigorous research designs are needed to assist in the rehabilitation of such patients.

Friend effects framework: Contrastive and hierarchical processing in cheerleader effects.

Cheerleader effects, group attractiveness effects, and divisive normalization are all characterized by faces appearing more attractive when seen within a group. However, it is possible that your friends could have a detrimental effect upon your attractiveness too: if these group effects arose partly as a contrastive process between your face and your friends, then highly attractive friends may diminish your attractiveness. We confirm this hypothesis across two experiments by showing that the presence of highly attractive friends can indeed make you appear less attractive (i.e., a reverse cheerleader effect), suggesting friend effects are driven in part by a contrastive process against the group. However, these effects are also influenced by your own attractiveness in a fashion that appears consistent with hierarchical encoding, where less attractive targets benefit more from being viewed in an increasingly unattractive group than attractive targets. Our final experiment demonstrates that the company of others not only alters our attractiveness, but also induces shifts in how average or distinctive a target face appears too, with these averageness effects associated with the friend effects observed in our first experiment. We present a Friend Effects Framework within which 'friend effects' is an umbrella term for the positive (e.g., cheerleader effects, group attractiveness effects) and negative (i.e., the reverse cheerleader effect) ways in which hierarchical encoding, group contrastive effects, and other influences of friends can have on your attractiveness.

Sex Differences in Adverse Reactions to an Inactivated SARS-CoV-2 Vaccine Among Medical Staff in China.

Objective: We investigated whether there were sex differences in adverse reactions to an inactivated SARS-CoV-2 vaccine among medical staff in China. Methods: From 24 February to 7 March 2021 an online cross-sectional survey was conducted with a self-administered COVID-19 vaccine questionnaire among medical staff in Taizhou, China. In total, 1397 interviewees (1,107 women and 290 men) participated in the survey. Results: In our study, 178 (16.1%) women and 23 (7.9%) men reported adverse reactions following their first vaccination, and 169 (15.3%) women and 35 (12.1%) men reported adverse reactions following their second vaccination. After adjusting for confounding factors, adverse reactions to other vaccines, worry about adverse reactions, knowledge of the inactivated vaccine being used in the hospital, taking the vaccine for one's family proactively and receiving an influenza vaccination were significantly related to adverse reactions to both injections in women. In contrast, in men, concerns about adverse reactions independently increased the risk of adverse reactions following either vaccination, and a history of adverse reactions to other vaccines also increased the risk of adverse reactions to both injections. Conclusions: Sex differences in the frequency of reported adverse reactions to an inactivated SARS-CoV-2 vaccine and potential factors were demonstrated in a sample of medical staff.

ΔPCO2 and ΔPCO2/C(a-cv)O2 Are Not Predictive of Organ Dysfunction After Cardiopulmonary Bypass.

Background: Cardiac surgery is associated with a substantial risk of major adverse events. Although carbon dioxide (CO2)-derived variables such as venous-to-arterial CO2 difference (ΔPCO2), and PCO2 gap to arterial-venous O2 content difference ratio (ΔPCO2/C(a-cv)O2) have been successfully used to predict the prognosis of non-cardiac surgery, their prognostic value after cardiopulmonary bypass (CPB) remains controversial. This hospital-based study explored the relationship between ΔPCO2, ΔPCO2/C(a-cv)O2 and organ dysfunction after CPB. Methods: We prospectively enrolled 114 intensive care unit patients after elective cardiac surgery with CPB. Patients were divided into the organ dysfunction group (OI) and non-organ dysfunction group (n-OI) depending on whether organ dysfunction occurred or not at 48 h after CPB. ΔPCO2 was defined as the difference between central venous and arterial CO2 partial pressure. Results: The OI group has 37 (32.5%) patients, 27 of which (23.7%) had one organ dysfunction and 10 (8.8%) had two or more organ dysfunctions. No statistical significance was found (P = 0.84) for ΔPCO2 in the n-OI group at intensive care unit (ICU) admission (9.0, 7.0-11.0 mmHg), and at 4 (9.0, 7.0-11.0 mmHg), 8 (9.0, 7.0-11.0 mmHg), and 12 h post admission (9.0, 7.0-11.0 mmHg). In the OI group, ΔPCO2 also showed the same trend [ICU admission (9.0, 8.0-12.8 mmHg) and 4 (10.0, 7.0-11.0 mmHg), 8 (10.0, 8.5-12.5 mmHg), and 12 h post admission (9.0, 7.3-11.0 mmHg), P = 0.37]. No statistical difference was found for ΔPCO2/C(a-cv)O2 in the n-OI group (P = 0.46) and OI group (P = 0.39). No difference was detected in ΔPCO2, ΔPCO2/C(a-cv)O2 between groups during the first 12 h after admission (P > 0.05). Subgroup analysis of the patients with two or more failing organs compared to the n-OI group showed that the predictive performance of lactate and Base excess (BE) improved, but not of ΔPCO2 and ΔPCO2/C(a-cv)O2. Regression analysis showed that the BE at 8 h after admission (odds ratio = 1.37, 95%CI: 1.08-1.74, P = 0.009) was a risk factor for organ dysfunction 48 h after CBP. Conclusion : ΔPCO2 and ΔPCO2/C(a-cv)O2 cannot be used as reliable indicators to predict the occurrence of organ dysfunction at 48 h after CBP due to the pathophysiological process that occurs after CBP.

An unsymmetrical binuclear iminopyridine-iron complex and its catalytic isoprene polymerization.

A series of chloride-bridged unsymmetrical mixed Fe(ii)-HS/Fe(ii)-LS binuclear structures has been prepared and characterized. Upon activation with MAO, highly efficient catalytic polymerization of isoprene was achieved, delivering an ultra-high molecular weight (catalyst loading = 2.5 ppm, Mn = 1.8 × 106 g mol-1, Mw/Mn = 1.4).

Dynamics of peripheral immune cells and their HLA-G and receptor expressions in a patient suffering from critical COVID-19 pneumonia to convalescence.

OBJECTIVES: Host immune responses are indispensable to combat the disease. We report the dynamics of peripheral immune cells, cytokines, and human leucocyte antigen-G (HLA-G) and its receptor expressions in a patient suffering from critical COVID-19 pneumonia to convalescence. METHODS: Clinical data of the patient were collected from medical records. The expressions of HLA-G and receptors ILT2, ILT4 and KIR2DL4 in peripheral immune cells were measured with flow cytometry. RESULTS: From critical COVID-19 to the convalescent stage, early lymphopenia was improved (median: 0.6 × 109 L-1 vs. 0.9 × 109 L-1, P = 0.009), and an obvious fluctuation in WBC and neutrophil counts was observed. Initially, low levels of CD4+ T cells (from 120 to 528 µL-1) and CD8+ T cells (from 68 to 362 µL-1) gradually increased to normal levels. Meanwhile, high IL-6 (from 251.8 to 6.32 pg mL-1), IL-10 (from 39.53 to 5.21 pg mL-1) and IFN-γ (from 13.55 to 3.16 pg mL-1) levels decreased, and IL-4 (from 2.36 to 3.19 pg mL-1) and TNF-α (from 2.27 to 20.2 pg mL-1) levels increased quickly when the viral RNA returned negative. Moreover, the percentage of HLA-G+ T cells, B cells and monocytes follows high-low-high pattern, while the percentage of receptors ILT2-, ILT4- and KIR2DL4-expressing cells remained relatively stable. CONCLUSION: Our findings provide valuable information on the dynamics of early peripheral immunological responses in SARS-CoV-2 infection. CD4+ and CD8+ T cells, cytokines and HLA-G+ immune cells are associated with the natural history of the critical COVID-19 patient; however, future studies are necessary.

Novel potent inhibitors of hepatitis C virus (HCV) NS3 protease with cyclic sulfonyl P3 cappings.

Extensive SAR studies of the P3 capping group led to the discovery of a series of potent inhibitors with sultam and cyclic sulfonyl urea moieties as the P3 capping. The bicyclic thiophene-sultam or phenyl-sultam cappings were selected for further SAR development. Modification at the P3 side chain determined that the tert-butyl group was the best choice at that position. Optimization of P1 residue significantly improved potency and selectivity. The combination of optimal moieties at all positions led to the discovery of compound 33. This compound had the best overall profile in potency and PK profile: excellent K(i)(*) of 5.3 nM and activity in replicon (EC(90)) of 80 nM, extremely high selectivity of 6100, and a good rat PO AUC of 1.43 microMh.

Potent and selective small molecule NS3 serine protease inhibitors of Hepatitis C virus with dichlorocyclopropylproline as P2 residue.

Starting from a pentapeptide Hepatitis C virus NS3 protease inhibitor, a number of alpha-ketoamide inhibitors based on novel dichlorocyclopropylproline P2 core were synthesized and investigated for their HCV NS3 serine protease activity. The key intermediate 3,4-dichlorocyclopropylproline was obtained through a dichloro carbene insertion to 3,4-dehydroproline. The size of the molecules was reduced significantly through a series of truncations of the initial pentapeptide. By varying P1 side chain in length and size, potency and selectivity were improved. A variety of aliphatic carbamate and urea capping groups were examined. In general, compounds with urea cappings were more potent and selective than their carbamate counterparts. The most potent compound was a tert-butyl urea analog. Variations at P3 position were also investigated. Among the three residues incorporated, tert-leucine was clearly superior, leading to compounds that had excellent enzyme potency and selectivity. The most potent compound achieved cell-based replicon assay EC50 of 40 nM. The most promising compound of all had excellent potency in both enzyme (Ki* = 9 nM) and replicon assays (EC50 = 100 nM). Its bioavailabilities were above 10% in all three animal species (rats, monkeys, and dogs). It has provided a lead for future investigations.

Novel potent hepatitis C virus NS3 serine protease inhibitors derived from proline-based macrocycles.

The hepatitis C virus (HCV) NS3 protease is essential for viral replication. It has been a target of choice for intensive drug discovery research. On the basis of an active pentapeptide inhibitor, 1, we envisioned that macrocyclization from the P2 proline to P3 capping could enhance binding to the backbone Ala156 residue and the S4 pocket. Thus, a number of P2 proline-based macrocyclic alpha-ketoamide inhibitors were prepared and investigated in an HCV NS3 serine protease continuous assay (K(i*)). The biological activity varied substantially depending on factors such as the ring size, number of amino acid residues, number of methyl substituents, type of heteroatom in the linker, P3 residue, and configuration at the proline C-4 center. The pentapeptide inhibitors were very potent, with the C-terminal acids and amides being the most active ones (24, K(i*) = 8 nM). The tetrapeptides and tripeptides were less potent. Sixteen- and seventeen-membered macrocyclic compounds were equally potent, while fifteen-membered analogues were slightly less active. gem-Dimethyl substituents at the linker improved the potency of all inhibitors (the best compound was 45, K(i*) = 6 nM). The combination of tert-leucine at P3 and dimethyl substituents at the linker in compound 47 realized a selectivity of 307 against human neutrophil elastase. Compound 45 had an IC(50) of 130 nM in a cellular replicon assay, while IC(50) for 24 was 400 nM. Several compounds had excellent subcutaneous AUC and bioavailability in rats. Although tripeptide compound 40 was 97% orally bioavailable, larger pentapeptides generally had low oral bioavailability. The X-ray crystal structure of compounds 24 and 45 bound to the protease demonstrated the close interaction of the macrocycle with the Ala156 methyl group and S4 pocket. The strategy of macrocyclization has been proved to be successful in improving potency (>20-fold greater than that of 1) and in structural depeptization.

Discovery of (1R,5S)-N-[3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]- 3-[2(S)-[[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]- 6,6-dimethyl-3-azabicyclo[3.1.0]hexan-2(S)-carboxamide (SCH 503034), a selective, potent, orally bioavailable hepatitis C virus NS3 protease inhibitor: a potential therapeutic agent for the treatment of hepatitis C infection.

Hepatitis C virus (HCV) infection is the major cause of chronic liver disease, leading to cirrhosis and hepatocellular carcinoma, which affects more than 170 million people worldwide. Currently the only therapeutic regimens are subcutaneous interferon-alpha or polyethylene glycol (PEG)-interferon-alpha alone or in combination with oral ribavirin. Although combination therapy is reasonably successful with the majority of genotypes, its efficacy against the predominant genotype (genotype 1) is moderate at best, with only about 40% of the patients showing sustained virological response. Herein, the SAR leading to the discovery of 70 (SCH 503034), a novel, potent, selective, orally bioavailable NS3 protease inhibitor that has been advanced to clinical trials in human beings for the treatment of hepatitis C viral infections is described. X-ray structure of inhibitor 70 complexed with the NS3 protease and biological data are also discussed.

Structure-activity relationship (SAR) development and discovery of potent indole-based inhibitors of the hepatitis C virus (HCV) NS5B polymerase.

Starting with the indole-based C-3 pyridone lead HCV polymerase inhibitor 2, extensive SAR studies were performed at different positions of the indole core. The best C-5 groups were found to be compact and nonpolar moieties and that the C-6 attachments were not affecting potency. Limited N-1 benzyl-type substituent studies indicated that the best substitutions were fluoro or methyl groups at 2' or 5' positions of the benzyl group. To improve pharmacokinetic (PK) properties, acylsulfonamides were incorporated as acid isosteres at the C-2 position. Further optimization of the combination at N-1, C-2, C-5, and C-6 resulted in the identification of compound 56, which had an excellent potency in both NS5B enzyme (IC(50) = 0.008 µM) and cell-based replicon (EC(50) = 0.02 µM) assays and a good oral PK profile with area-under-the curve (AUC) of 14 and 8 µM·h in rats and dogs, respectively. X-ray structure of inhibitor 56 bound to the enzyme was also reported.

A novel class of highly potent irreversible hepatitis C virus NS5B polymerase inhibitors.

Starting from indole-based C-3 pyridone HCV NS5B polymerase inhibitor 2, structure-activity relationship (SAR) investigations of the indole N-1 benzyl moiety were performed. This study led to the discovery of irreversible inhibitors with p-fluoro-sulfone- or p-fluoro-nitro-substituted N-1 benzyl groups which achieved breakthrough replicon assay potency (EC(50) = 1 nM). The formation of a covalent bond with adjacent cysteine-366 thiol was was proved by mass spectroscopy and X-ray crystal structure studies. The C-5 ethyl C-2 carboxylic acid derivative 47 had an excellent oral area-under-the-curve (AUC) of 18 µM·h (10 mg/kg). Its oral exposure in monkeys and dogs was also very good. The NMR ALARM assay, mass spectroscopy experiments, in vitro counter screening, and toxicology assays demonstrated that the covalent bond formation between compound 47 and the protein was highly selective and specific. The overall excellent profile of 47 made it an interesting candidate for further investigation.