An E3 ubiquitin ligase localization screen uncovers DTX2 as a novel ADP-ribosylation-dependent regulator of DNA double-strand break repair.

DNA double-strand breaks (DSBs) elicit an elaborate response to signal damage and trigger repair via two major pathways: nonhomologous end-joining (NHEJ), which functions throughout the interphase, and homologous recombination (HR), restricted to S/G2 phases. The DNA damage response relies, on post-translational modifications of nuclear factors to coordinate the mending of breaks. Ubiquitylation of histones and chromatin-associated factors regulates DSB repair and numerous E3 ubiquitin ligases are involved in this process. Despite significant progress, our understanding of ubiquitin-mediated DNA damage response regulation remains incomplete. Here, we have performed a localization screen to identify RING/U-box E3 ligases involved in genome maintenance. Our approach uncovered 7 novel E3 ligases that are recruited to microirradiation stripes, suggesting potential roles in DNA damage signaling and repair. Among these factors, the DELTEX family E3 ligase DTX2 is rapidly mobilized to lesions in a poly ADP-ribosylation-dependent manner. DTX2 is recruited and retained at DSBs via its WWE and DELTEX conserved C-terminal domains. In cells, both domains are required for optimal binding to mono and poly ADP-ribosylated proteins with WWEs playing a prominent role in this process. Supporting its involvement in DSB repair, DTX2 depletion decreases HR efficiency and moderately enhances NHEJ. Furthermore, DTX2 depletion impeded BRCA1 foci formation and increased 53BP1 accumulation at DSBs, suggesting a fine-tuning role for this E3 ligase in repair pathway choice. Finally, DTX2 depletion sensitized cancer cells to X-rays and PARP inhibition and these susceptibilities could be rescued by DTX2 reexpression. Altogether, our work identifies DTX2 as a novel ADP-ribosylation-dependent regulator of HR-mediated DSB repair.

[Mandibular osteotomy, a simpler and safer method of osteosynthesis]. / Ostéotomie mandibulaire, une méthode plus simple et plus sûre d'ostéosynthèse.

Bilateral sagittal split osteotomy (BSSO) is a surgical procedure to treat mandibular malpositions. However, this surgery is associated with a risk of recurrence. Osteosynthesis techniques may be the cause of early recurrences. This study aims to demonstrate the efficiency and stability of osteosynthesis with two bicortical screws placed with a transjugal approach. We included patients who benefited from a BSSO alone, between May 2020 and August 2021. We performed the osteosynthesis using two bicortical screws placed with a transjugal approach. All the patients underwent lateral X-rays before the surgery, one week after and minimum six months after the intervention. These medical images allowed to study the mandibular movements during the intervention and the osteosynthesis stability. Twenty-five patients benefited from a BSSO alone. Patients obtained a satisfactory occlusal result. The results showed good stability of the two fragments, after surgery, during the studied period (average follow up of 8 months). Two bicortical screws osteosynthesis placed with a transjugal approach is a simple, effective and stable method for osteosynthesis in case of BSSO.

Les ostéotomies sagittales bilatérales mandibulaires (OSBM) sont des procédures chirurgicales utilisées pour traiter les malpositions mandibulaires. Toutefois, cette chirurgie présente un risque de récidive. Les techniques d'ostéosynthèse pourraient être la cause de récidives précoces. Cette étude vise à démontrer l'efficacité et la stabilité de l'ostéosynthèse à l'aide de deux vis bicorticales placées par voie transjugale. Nous avons inclus les patients ayant bénéficié d'une OSBM seule, entre mai 2020 et août 2021. Nous avons réalisé les ostéosynthèses à l'aide de deux vis bicorticales placées par voie transjugale. Tous les patients ont réalisé des clichés radiologiques de profil avant l'intervention, une semaine après et minimum six mois après. Ces imageries ont permis d'étudier les mouvements mandibulaires durant l'intervention et la stabilité de l'ostéosynthèse. Vingt-cinq patients ont bénéficié d'une OSBM seule. Les patients ont obtenu un résultat occlusal satisfaisant. Les résultats ont montré une bonne stabilité des deux fragments après la chirurgie durant la période étudiée (en moyenne, recul de 8 mois). En conclusion, l'ostéosynthèse à l'aide de deux vis placées par voie transjugale est une méthode simple, efficace et stable d'ostéosynthèse d'OSBM.

Total Capital Investment of plastic recycling plants correlates with energy losses and capacity.

Plastic pollution is a generational problem, and stakeholders are turning to chemical recycling as a potential solution. However, decision-makers necessitate quick and reliable capital investment estimations to evaluate innovative technologies, especially in the early project stage, when limited historical data are available. To address this need, we built a database of 160+ chemical recycling plants, querying for nominal capacity, year and place of construction, total capital investment (TCI), number of long-term jobs and opportunity of subsidies. Then, we compared conventional association of the advancement of cost engineering AACE class 5 estimation methods, with literature estimates, and commercial capital expenditure confidence intervals for pyrolysis, gasification, solvolysis, and selective dissolution. We demonstrate the unreliability of classic methods, and we propose ballpark correlations based on the plant capacity, or the energy loss. Chemical recycling plants suffer from poor economy of scale (with current technologies), and capacity is not always the best indicator for TCI estimation. Pyrolysis and gasification are energy-driven technologies, and their TCI correlates very well (R2 =0.91-0.92) with the total energy losses. Solvolysis and selective dissolution, instead, are at an earlier development stage, so cost engineers or researchers will have to accept less certain TCI vs capacity (R2 =0.60).

Multiparametric MR Evaluation of the Photoperiodic Regulation of Hypothalamic Structures in Sheep.

Most organisms on earth, humans included, have developed strategies to cope with environmental day-night and seasonal cycles to survive. For most of them, their physiological and behavioral functions, including the reproductive function, are synchronized with the annual changes of day length, to ensure winter survival and subsequent reproductive success in the following spring. Sheep are sensitive to photoperiod, which also regulates natural adult neurogenesis in their hypothalamus. We postulate that the ovine model represents a good alternative to study the functional and metabolic changes occurring in response to photoperiodic changes in hypothalamic structures of the brain. Here, the impact of the photoperiod on the neurovascular coupling and the metabolism of the hypothalamic structures was investigated at 3T using BOLD fMRI, perfusion-MRI and proton magnetic resonance spectroscopy (1H-MRS). A longitudinal study involving 8 ewes was conducted during long days (LD) and short days (SD) revealing significant BOLD, rCBV and metabolic changes in hypothalamic structures of the ewe brain between LD and SD. More specifically, the transition between LD and SD revealed negative BOLD responses to hypercapnia at the beginning of SD period followed by significant increases in BOLD, rCBV, Glx and tNAA concentrations towards the end of the SD period. These observations suggest longitudinal mechanisms promoting the proliferation and differentiation of neural stem cells within the hypothalamic niche of breeding ewes. We conclude that multiparametric MRI studies including 1H-MRS could be promising non-invasive translational techniques to investigate the existence of natural adult neurogenesis in-vivo in gyrencephalic brains.

Seasonal remodeling of the progenitor pool and its distribution in the ewe mediobasal hypothalamus.

Recent studies have reported the presence of adult neurogenesis in the arcuate nucleus periventricular space (pvARH) and in the median eminence (ME), two structures involved in reproductive function. In sheep, a seasonal mammal, decreasing daylight in autumn induces a higher neurogenic activity in these two structures. However, the different types of neural stem and progenitor cells (NSCs/NPCs) that populate the arcuate nucleus and median eminence, as well as their location, have not been evaluated. Here, using semi-automatic image analyzing processes, we identified and quantified the different populations of NSCs/NPCs, showing that, during short days, higher densities of [SOX2 +] cells are found in pvARH and ME. In the pvARH, higher densities of astrocytic and oligodendrocitic progenitors mainly contribute to these variations. The different populations of NSCs/NPCs were mapped according to their position relative to the third ventricle and their proximity to the vasculature. We showed that [SOX2 +] cells extended deeper into the hypothalamic parenchyma during short days. Similarly, [SOX2 +] cells were found further from the vasculature in the pvARH and the ME, at this time of year, indicating the existence of migratory signals. The expression levels of neuregulin transcripts (NRGs), whose proteins are known to stimulate proliferation and adult neurogenesis and to regulate progenitor migration, as well as the expression levels of ERBB mRNAs, cognate receptors for NRGs, were assessed. We showed that mRNA expression changed seasonally in pvARH and ME, suggesting that the ErbB-NRG system is potentially involved in the photoperiodic regulation of neurogenesis in seasonal adult mammals.

Ozone exposure-response relationships parametrized for sixteen tree species with varying sensitivity in the United States.

It is well known that exposure to ambient O3 can decrease growth in many tree species in the United States (US). Our study reports experimental data from outdoor open-top chamber (OTC) studies that quantify total biomass response changes for seedlings of 16 species native to western and eastern North America, which were exposed to several levels of elevated O3 for one or more years. The primary objective of this study is to establish a reference set of parameters for these seedling exposure-response relationships using a 3-month (92 day) 12-hr W126 O3 metric used by US Environmental Protection Agency and other agencies to assess risk to trees from O3 exposure. We classified the 16 species according to their sensitivity, based on the biomass loss response functions to protect from a 5% biomass loss. The three-month 12-h W126 estimated to result in a 5% biomass loss was 2.5-9.2 ppm-h for sensitive species, 20.8-25.2 ppm-h for intermediate species, and > 28.7 ppm-h for insensitive species. The most sensitive tree species include black cherry, ponderosa pine, quaking aspen, red alder, American sycamore, tulip poplar and winged sumac. These species are ecologically important and widespread across US. The effects of O3 on whole-plant biomass depended on exposure duration and dynamics and on the number of successive years of exposure. These species-specific exposure-response relationships will allow US agencies and other groups to better estimate biomass losses based on ozone exposures in North America and can be used in risk assessment and scenario analyses.

Al4Ir: An Al-Ir Binary-Phase Superstructure of the Ni2Al3 Type.

A binary phase with Al4Ir composition has been discovered in the Al-Ir binary system. Single-crystal X-ray diffraction analysis reveals that it crystallizes in the trigonal space group P3c1 with the unit cell parameters a = 12.8802(2) Å and c = 9.8130(2) Å. This structure is derived from the Ni2Al3 structure type. The supercell is due to the ordering of the aluminum atoms, which replace the nickel atoms in the prototype structure. The crystal structure was directly imaged by atomic-scale scanning transmission electron microscopy, and the misalignment of the Al site responsible for the supercell has been clearly evidenced. Its metastable nature has been confirmed by differential thermal analysis measurements. The atomic and electronic structures of Al4Ir have also been investigated by density functional theory. The structural optimization leads to lattice parameters and atomic positions in good agreement with the experimental ones. The compound is metallic, with a minimum in the density of states located more than 1 eV above the Fermi energy. This suggests a metastable system, in agreement with the electron count found much above 18 electrons per Ir atom, deviating from the Hume-Rothery rule and with the presence of occupied antibonding states revealed by the crystal orbital Hamiltonian population analysis. The relative stability of the compound is ensured by the hybridization between sp-Al and d-Ir states within Ir-centered clusters, while covalent-like interactions in-between the clusters are indicated by the analysis of the electron localizability function.

Seasonal vascular plasticity in the mediobasal hypothalamus of the adult ewe.

Sheep, like most seasonal mammals, exhibit a cyclic adaptive reproductive physiology that allows ewes to give birth to their progeny during the spring when environmental conditions are favorable to their survival. This process relies on the detection of day length (or photoperiod) and is associated with profound changes in cellular plasticity and gene expression in the hypothalamic-pituitary-gonadal axis, mechanisms that are suggested to participate in the seasonal adaptation of neuroendocrine circuits. Recently, pituitary vascular growth has been proposed as a seasonally regulated process in which the vascular endothelial growth factor A (VEGFA), a well-known angiogenic cytokine, is suspected to play a crucial role. However, whether this mechanism is restricted to the pituitary gland or also occurs in the mediobasal hypothalamus (MBH), a crucial contributor to the control of the reproductive function, remains unexplored. Using newly developed image analysis tools, we showed that the arcuate nucleus (ARH) of the MBH exhibits an enhanced vascular density during the long photoperiod or non-breeding season, associated with higher expression of VEGFA. In the median eminence (ME), a structure connecting the MBH to the pituitary gland, higher VEGFA, kinase insert domain receptor (KDR/VEGFR2) and plasmalemma vesicle-associated protein (PLVAP) gene expressions were detected during the long photoperiod. We also found that VEGFA and its receptor, VEGFR2, are expressed by neurons and tanycytes in both the ARH and ME. Altogether, these data show variations in the MBH vasculature according to seasons potentially through a VEGFA-dependent pathway, paving the way for future studies aiming to decipher the role of these changes in the hypothalamic control of seasonal reproduction.

Risk Analysis on PMMA Recycling Economics.

Poly(methyl methacrylate) (PMMA) is a versatile polymer with a forecast market of 4 Mtons/y by 2025, and 6 USD billion by 2027. Each year, 10% of the produced cast sheets, extrusion sheets, or granules PMMA end up as post-production waste, accounting for approximately 30 000 tons/y in Europe only. To guide the future recycling efforts, we investigated the risks of depolymerization process economics for different PMMA scraps feedstock, capital expenditure (CAPEX), and regenerated MMA (r-MMA) prices via a Monte-Carlo simulation. An analysis of plastic recycling plants operating with similar technologies confirmed how a maximum 10 M USD plant (median cost) is what a company should aim for, based on our hypothesis. The capital investment and the r-MMA quality have the main impacts on the profitability. Depending on the pursued outcome, we identified three most suitable scenarios. Lower capital-intensive plants (Scenarios 4 and 8) provide the fastest payback time, but this generates a lower quality monomer, and therefore lower appeal on the long term. On 10 or 20 years of operation, companies should target the very best r-MMA quality, to achieve the highest net present value (Scenario 6). Product quality comes from the feedstock choice, depolymerization, and purification technologies. Counterintuitively, a plant processing low quality scraps available for free (Scenario 7), and therefore producing low purity r-MMA, has the highest probability of negative net present value after 10 years of operation, making it a high-risk scenario. Western countries (especially Europe), call for more and more pure r-MMA, hopefully comparable to the virgin material. With legislations on recycled products becoming more stringent, low quality product might not find a market in the future. To convince shareholders and government bodies, companies should demonstrate how funds and subsidies directly translate into higher quality products (more attractive to costumers), more economically viable, and with a wider market.

Improving patient self-reporting of antihypertensive adverse drug events in primary care: a stepped wedge cluster randomised trial.

BACKGROUND: About 25% of patients experience adverse drug events (ADE) in primary care, but few events are reported by the patients themselves. One solution to improve the detection and management of ADEs in primary care is for patients to report them to their general practitioner. The study aimed to assess the effect of a booklet designed to improve communication and interaction between patients treated with anti-hypertensive drugs and general practitioners on the reporting of ADEs. METHODS: A cluster randomized controlled cross-sectional stepped wedge open trial (five periods of 3 months) was conducted. A cluster was a group of general practitioners working in ambulatory offices in France. Adults consulting their general practitioner to initiate, modify, or renew an antihypertensive prescription were included. A booklet including information on cardiovascular risks, antihypertensive treatments, and ADE report forms was delivered by the general practitioner to the patient in the intervention group. The primary outcome was the reporting of at least one ADE by the patient to his general practitioner during the three-month period after enrolment. Two clusters were randomised by sequence for a total of 8 to receive the intervention. An intention-to-treat analysis was conducted. A logistic mixed model with random intercept was used. RESULTS: Sixty general practitioners included 1095 patients (median: 14 per general practitioner; range: 1-103). More patients reported at least one ADE to their general practitioner in the intervention condition compared to the control condition (aOR = 3.5, IC95 [1.2-10.1], p = 0.02). The modification and initiation of an antihypertensive treatment were also significantly associated with the reporting of ADEs (aOR = 4.4, CI95 [1.9-10.0], p <  0.001 and aOR = 11.0, CI95 [4.6-26.4], p <  0.001, respectively). The booklet delivery also improved patient satisfaction on general practitioner communication and high blood pressure management. CONCLUSION: A booklet can improve patient self-reporting of ADEs to their general practitioners. Future research should assess whether it can improve general practitioner management of ADEs and patient's health status. TRIAL REGISTRATION: Trial registry identifier NCT01610817 (2012/05/30).

Negative regulation of melatonin secretion by melatonin receptors in ovine pinealocytes.

Melatonin (MLT) is a biological modulator of circadian and seasonal rhythms and reproduction. The photoperiodic information is detected by retinal photoreceptors and transmitted through nerve transmissions to the pineal gland, where MLT is synthesized and secreted at night into the blood. MLT interacts with two G protein-coupled receptors, MT1 and MT2. The aim of our work was to provide evidence for the presence of MLT receptors in the ovine pineal gland and define their involvement on melatonin secretion. For the first time, we identified the expression of MLT receptors with the specific 2-[125I]-MLT agonistic radioligand in ovin pinealocytes. The values of Kd and Bmax are 2.24 ± 1.1 nM and 20 ± 6.8 fmol/mg. MLT receptors are functional and inhibit cAMP production and activate ERK1/2 through pertussis toxin-sensitive Gi/o proteins. The MLT receptor antagonist/ inverse agonist luzindole increased cAMP production (189 ± 30%) and MLT secretion (866 ± 13%). The effect of luzindole on MLT secretion was additive with the effect of well-described activators of this pathway such as the ß-adrenergic agonist isoproterenol and the α-adrenergic agonist phenylephrine. Co-incubation of all three compounds increased MLT secretion by 1236 ± 199%. These results suggest that MLT receptors are involved in the negative regulation of the synthesis of its own ligand in pinealocytes. While adrenergic receptors promote MLT secretion, MLT receptors mitigate this effect to limit the quantity of MLT secreted by the pineal gland.

Blood oxygen level dependent fMRI and perfusion MRI in the sheep brain.

The ovine model could be an effective translational model but remains underexplored. Here, Blood Oxygen Level dependent functional MRI during visual stimulation and resting-state perfusion MRI were explored. We aimed at investigating the impact of isoflurane anesthesia during visual stimulation and evaluate resting cerebral blood flow and cerebral blood volume parameters in the lamb and adult sheep brain. BOLD fMRI and perfusion MRI after a bolus of DOTAREM were conducted in 4 lambs and 6 adult ewes at 3 T. A visual stimulation paradigm was delivered during fMRI at increasing isoflurane doses (1-3%). Robust but weak BOLD responses (0.21 ± 0.08%) were found in the lateral geniculate nucleus (LGN) up to 3% isoflurane anaesthesia. No significant differences were found beween BOLD responses in the range 1 to 3% ISO (p > 0.05). However, LGN cluster size decreased and functional localization became less reliable at high ISO doses (2.5-3% ISO). BOLD responses were weaker in adult sheep than in lambs (4.6 ± 1.5 versus 13.6 ± 8.5; p = 0.08). Relative cerebral blood volumes (rCBV) and relative cerebral blood flows (rCBF) were significantly higher (p < 0.0001) in lambs than in adult sheep for both gray and white matter. The impact of volatile anesthesia was explored for the first time on BOLD responses demonstrating increased reliability of functional localization of brain activity at low doses. Perfusion MRI was conducted for the first time in both lambs and adult ewes. Assessment of baseline cerebrovascular values are of interest for future studies of brain diseases allowing an improved interpretation of BOLD responses.

Chemerin impairs food intake and body weight in chicken: Focus on hypothalamic neuropeptides gene expression and AMPK signaling pathway.

Unlike mammals, the role of adipokines and more particularly of chemerin in the regulation of food intake is totally unknown in avian species. Here we investigated the effect of chemerin on the food and water consumption and on the body weight in chicken. We studied the effects on the plasma glucose and insulin concentrations and the hypothalamic neuropeptides and AMPK signaling pathway. Female broiler chickens were intraperitoneally injected, daily for 13 days with either vehicle (saline; n = 25) or chemerin (8 µg/kg; n = 25 and 16 µg/kg; n = 25). Food and water intakes were recorded 24 h after each administration. Overnight fasted animals were sacrificed at day 13 (D13), 24 h after the last injection and hypothalamus and left cerebral hemispheres were collected. Chemerin and its receptors protein levels were determined by western-blot. Gene expression of neuropeptide Y (Npy), agouti-related peptide (Agrp), corticotrophin releasing hormone (Crh), pro-opiomelanocortin (Pomc), cocaine and amphetamine-regulated transcript (Cart) and Taste 1 Receptor Member 1 (Tas1r1) were evaluated by RT-qPCR. In chicken, we found that the protein amount of chemerin, CCRL2 and GPR1 was similar in left cerebral hemisphere and hypothalamus whereas CMKLR1 was higher in hypothalamus. Chemerin administration (8 and 16 µg/kg) decreased both food intake and body weight compared to vehicle without affecting water intake and the size or volume of different brain subdivisions as determined by magnetic resonance imaging. It also increased plasma insulin levels whereas glucose levels were decreased. These data were associated with an increase in Npy and Agrp expressions and a decrease in Crh, Tas1r1 mRNA expression within the hypothalamus. Furthermore, chemerin decreased hypothalamic CMKLR1 protein expression and AMPK activation. Taken together, these results support that chemerin could be a peripheral appetite-regulating signal through modulation of hypothalamic peptides expression in chicken.

Conversion of fatty acid methyl esters into dibasic esters by metathesis and their lubricant properties.

Biodiesel plants are struggling to find value added applications for fatty acid methyl esters (FAME). One option for FAME valorization would be dibasic esters, which can be transesterified with 2-ethylhexyl (2EH) or other alcohols to produce lubricant basestocks and achieve the most widespread viscosity grades VG46 and VG32. Biocatalytic, metathesis and other synthetic pathways are available to produce dibasic esters. Using a ruthenium-based catalyst, methyl oleate was converted into monounsaturated dibasic ester by metathesis and reached VG22 after transesterification with 2EH in this investigation. Synthesized 2EH esters of other dibasic acids showed distinct viscometric trends. Their correlation implied that FAME from gondoic and erucic acids should result in VG32 and VG46 respectively, if converted into 2EH dibasic esters. Pour points demonstrated excellent low temperature fluidity and resistance to heat thinning when monounsaturation was retained. Oxidative stability properties remained acceptable, volatility was lower than that of VG46 mineral oils. Mixed alcohols, acids and esters can also be used for meeting VG specifications or achieving higher biobased contents. Currently petrochemical ester basestocks dominate in high performance hydraulic fluids (HF). However, fractionation of FAME into high-erucic/gondoic esters in biodiesel plants can produce a valuable biobased feedstock for large volume manufacture of HF and other lubricants.

Progress in Reaction Mechanisms and Reactor Technologies for Thermochemical Recycling of Poly(methyl methacrylate).

Chemical or feedstock recycling of poly(methyl methacrylate) (PMMA) by thermal degradation is an important societal challenge to enable polymer circularity. The annual PMMA world production capacity is over 2.4 × 106 tons, but currently only 3.0 × 104 tons are collected and recycled in Europe each year. Despite the rather simple chemical structure of MMA, a debate still exists on the possible PMMA degradation mechanisms and only basic batch and continuous reactor technologies have been developed, without significant knowledge of the decomposition chemistry or the multiphase nature of the reaction mixture. It is demonstrated in this review that it is essential to link PMMA thermochemical recycling with the PMMA synthesis as certain structural defects from the synthesis step are affecting the nature and relevance of the subsequent degradation reaction mechanisms. Here, random fission plays a key role, specifically for PMMA made by anionic polymerization. It is further highlighted that kinetic modeling tools are useful to further unravel the dominant PMMA degradation mechanisms. A novel distinction is made between global conversion or average chain length models, on the one hand, and elementary reaction step-based models on the other hand. It is put forward that only by the dedicated development of the latter models, the temporal evolution of degradation product spectra under specific chemical recycling conditions will become possible, making reactor design no longer an art but a science.

Crystalline and Electronic Structures of the Al1+xV2Sn2-x (x = 0.19) Intermetallic Compound.

A new ternary phase with a composition Al1+xV2Sn2-x (x = 0.19) has been found during investigation of the Al-V-Sn ternary system. Single-crystal X-ray diffraction measurements reveal that this ternary phase crystallizes with an orthorhombic structure with a = 5.5931(1) Å, b = 18.8017(5) Å, and c = 6.7005(2) Å (space group Cmce). This compound is thus isostructural to the GaV2Sn2 structure type, showing a layered structure composed of vanadium cluster bands formed with pentagonal faces intercalated by Sn atom layers. High-resolution transmission electron microscopy measurements confirm the orthorhombic structure. Regarding lattice perfection, no dislocation could be identified within the probed Al1.19V2Sn1.81 single-crystal lamella. Ab initio calculations reveal a reduction of the density of states at the Fermi level, which could be attributed to both a Hume-Rothery effect combined with strong spd hybridization.

Epidemic Diseases and Chinese Medicine: Example of SARS and COVID-19: Part Two.

Along with the legends about epidemic demons, China has developed over the centuries a medical approach to epidemic diseases based on the teachings of Huang Di Nei Jing ( Huangdi's Internal Classic), Nan Jing ( Classic of Difficult Issues), and Shang Han Lun ( Treatise on Cold Damage). Other doctors and scientists participated in this evolution of knowledge, like Wang Shuhe (), Ge Hong (), Chao Yuanfang (), Sun Simiao (), and Liu Wansu (). However, it was in the 17th century, after the great break of the Song, Jin, and Yuan eras that an innovative spirit, Wu Youke ( 1582-1652) first foresaw the existence of microorganisms as we know them now. His Wen Yi Lun ( Treatise on Pestilence) foreshadows an original approach to epidemic diseases, particularly emerging infectious diseases of the 21st century. After them, traditional Chinese medicine developed a comprehensive method of diagnosing and treating of these diseases (Epidemic Diseases Theory ) within the School of Heat Diseases (). In a third article, we will examine some applications in the treatment of the SARS 2003-2004 epidemic () and the current COVID-19 () pandemic.

Epidemic Diseases and Chinese Medicine: Example of Severe Acute Respiratory Syndrome and COVID-19.

Epidemic diseases, known and studied in China since antiquity, are one of the main chapters of the School of Exogenous Febrile Diseases (). Along with the legends about epidemic demons, China has developed over the centuries a medical approach based on the teachings of Huang Di Nei Jing (Internal Classic), Nan Jing (Classic of Difficulties), and Shang Han Lun (Treatise of Harmful Cold). However, it was in the 17th century, after the great break of the Song, Jin, and Yuan eras that an innovative spirit Wu Youxing () first foresaw the existence of microorganisms as we know them now. His Wen Yi Lun (Treatise on Pestilences) foreshadows an original approach to epidemic diseases, particularly emerging infectious diseases of the 21st century: severe acute respiratory syndrome 2003-2004 and the COVID-19 pandemic are perfect examples. In this first article, which will be followed by two others, we will examine the classical and modern Chinese definitions of these dreadful plagues.

A Simple and Efficient Mechanochemical Route for the Synthesis of Salophen Ligands and of the Corresponding Zn, Ni, and Pd Complexes.

A number of salophen ligands and their Zn, Ni, and Pd complexes were synthesized by an efficient one-pot mechanosynthesis protocol. The reaction products were characterized by means of complementary solid-state techniques, i.e., powder X-ray diffraction, single-crystal X-ray diffraction, and solid-state NMR spectroscopy. Four new crystal structures of metal salophen complexes as DMSO solvates are here reported. The described simple and relatively fast (about 1 h for all derivatives) procedure is a good alternative to classical methods performed in organic solvents.

Coupling Rhodium-Catalyzed Hydroformylation of 10-Undecenitrile with Organic Solvent Nanofiltration: Toluene Solution versus Solvent-Free Processes.

Intensification of the rhodium-catalyzed hydroformylation process to produce 12-oxo-dodecanenitrile from biosourced 10-undecenitrile was performed by coupling the reaction with organic solvent nanofiltration (OSN) for the recycling of the expensive Rh catalyst and the ligands. Four phosphorus-based ligands were compared with respect to their catalytic performance and rejection in OSN. Biphephos showed the best compromise and up to 3 reaction-OSN cycles were performed in toluene. A good recycling of the catalytic system was evidenced arising from the OSN (up to 88 % rejection). In order to develop a greener process, a similar approach was achieved in bulk (i. e. solvent-free medium), thus proving the catalyst recycling feasibility but also that the optimal OSN conditions are not the same as for toluene. Finally, integration of OSN in the overall production process is discussed, aiming at the proposal of a hybrid separation process involving a combination of OSN and distillation for an energy-efficient separation step.