Ring Formation Research Articles

Bone resorption by osteoclasts involves fine tuning of RHOA activity by its microtubule-associated exchange factor GEF-H1.

Bone health is controlled by the balance between bone formation by osteoblasts and degradation by osteoclasts. A disequilibrium in favor of bone resorption leads to osteolytic diseases characterized by decreased bone density. Osteoclastic resorption is dependent on the assembly of an adhesion structure: the actin ring, also called podosome belt or sealing zone, which is composed of a unique patterning of podosomes stabilized by microtubules. A better understanding of the molecular mechanisms regulating the crosstalk between actin cytoskeleton and microtubules network is key to find new treatments to inhibit bone resorption. Evidence points to the importance of the fine tuning of the activity of the small GTPase RHOA for the formation and maintenance of the actin ring, but the underlying mechanism is not known. We report here that actin ring disorganization upon microtubule depolymerization is mediated by the activation of the RHOA-ROCK signaling pathway. We next show the involvement of GEF-H1, one of RHOA guanine exchange factor highly expressed in osteoclasts, which has the particularity of being negatively regulated by sequestration on microtubules. Using a CRISPR/Cas9-mediated GEF-H1 knock-down osteoclast model, we demonstrate that RHOA activation upon microtubule depolymerization is mediated by GEF-H1 release. Interestingly, although lower levels of GEF-H1 did not impact sealing zone formation in the presence of an intact microtubule network, sealing zone was smaller leading to impaired resorption. Altogether, these results suggest that a fine tuning of GEF-H1 through its association with microtubules, and consequently of RHOA activity, is essential for osteoclast sealing zone stability and resorption function.

Λ polarization from vortex rings as the medium response for jet thermalization

We performed a systematic study on the formation of vorticity rings as the process for jet thermalization in the medium created in high-energy nuclear collisions. In this work, we expanded our previous analysis to a more realistic framework by considering noncentral events and fluctuations in the initial condition. We simulate the formation and evolution of the flow vortex structure in a relativistic viscous hydrodynamic model and study the sensitivity of the proposed “ring observable” (RΛt) that can be measured experimentally through the polarization of Λ hyperons. We show that this observable is robust with respect to fluctuating initial conditions to capture the jet-induced vortex flow signal and further study its dependence on different model parameters, such as the jet's velocity, position, the fluid's shear viscosity, and the collision centrality. The proposed observable is associated with the formation of vorticity in a quark-gluon plasma, showing that the measurement of particle polarization can be a powerful tool to probe different properties of jet-medium interactions and to understand better the polarization induced by the transverse and longitudinal expansions of the medium. Published by the American Physical Society 2024

Reduced form of Galectin-1 Suppresses Osteoclastic Differentiation of Human Peripheral Blood Mononuclear Cells and Murine RAW264 Cells In Vitro.

Galectin-1 (Gal-1) is an evolutionarily conserved sugar-binding protein found in intra- and extracellular spaces. Extracellularly, it binds to glycoconjugates with β-galactoside(s) and functions in various biological phenomena, including immunity, cancer, and differentiation. Under extracellular oxidative conditions, Gal-1 undergoes oxidative inactivation, losing its sugar-binding ability, although it exhibits sugar-independent functions. An age-related decrease in serum Gal-1 levels correlates with decreasing bone mass, and Gal-1 knockout promotes osteoclastic bone resorption and suppresses bone formation. However, the effect of extracellular Gal-1 on osteoclast differentiation remains unclear. Herein, we investigated the effects of extracellular Gal-1 on osteoclastogenesis in human peripheral blood mononuclear cells (PBMCs) and mouse macrophage RAW264 cells. Recombinant Gal-1 suppressed the macrophage colony-stimulating factor and receptor activator of nuclear factor-κB ligand-dependent osteoclast formation, actin ring formation, and bone-resorption activity of human PBMCs. Similar results were obtained for RAW264 cells. Gal-1 knockdown increased osteoclast-like cell formation, suggesting that it affected differentiation in an autocrine-like manner. Oxidized Gal-1 slightly affected differentiation, and in the presence of lactose, the differentiation inhibitory effect of galectin-1 was not observed. These findings suggest that extracellular Gal-1 inhibits osteoclast differentiation in a β-galactoside-dependent manner, and an age-related decrease in serum Gal-1 levels may contribute to reduced osteoclast activity and decreasing bone mass.

Total Synthesis of Stachybotrys microspora Triprenol Phenol-7 (SMTP-7).

The first total synthesis of Stachybotrys microspora triprenol phenol (SMTP)-7 is described. Establishment of the two pyran ring stereogenic centers and key reactions featuring a double reductive amination and a double lactam ring formation in flow are described. The (2R,3S)-trans-benzopyran intermediate 7A, isolated by chiral preparative SFC chromatography, was carried forward to afford SMTP-7. Analytical data for synthetic SMTP-7, including 1H and 13C NMR data, HPLC retention time, and UV spectrum, were in excellent agreement with those for natural SMTP-7.

Specific and sequential detection of hydrogen sulfide and hypochlorous acid based on a ring-forming reaction and self-assembly

Some biological small molecules such as hydrogen sulfide (H2S) and hypochlorous acid (HClO), play pivotal roles in numerous biological and pathological processes and are associated with various diseases. The detection and monitoring them is of continued research interest. Here we report a sequential detection mode fluorescence probes that allow for the sensing of HS– and ClO–. The mixture of P and HS– constructs a specific sensing system S for ClO–. The substitution product S is stable in air, which also could be used independently. Mechanism studies demonstrate that HS– substitutes the Cl atom in P. Furthermore, the addition of ClO– facilitates a ring-forming reaction, resulting in the formation of a thiofuran ring within the product (T). Interestingly, P has a highly ordered steric packing and could self-assemble into a rice-spike-like structure. Upon the addition of HS–, the assemblies decompose into free molecules. After interaction with ClO–, these molecules further transform to T with strong assembled capacity, featuring a larger number of nanosheets. This study provides a novel mechanism for sensing HS– and ClO–, cell and living animal imaging further indicating the good application prospects of these probes in biosensing and bioimaging.

Active machine learning model for the dynamic simulation and growth mechanisms of carbon on metal surface

Substrate-catalyzed growth offers a highly promising approach for the controlled synthesis of carbon nanostructures. However, the growth mechanisms on dynamic catalytic surfaces and the development of more general design strategies remain ongoing challenges. Here we show how an active machine-learning model effectively reveals the microscopic processes involved in substrate-catalyzed growth. Utilizing a synergistic approach of molecular dynamics and time-stamped force-biased Monte Carlo methods, augmented by the Gaussian Approximation Potential, we perform fully dynamic simulations of graphene growth on Cu(111). Our findings accurately replicate essential subprocesses–from the preferred diffusion of carbon monomer/dimer, chain or ring formations to edge-passivated Cu-aided graphene growth and bond breaks by ion impacts. Extending our simulations to carbon deposition on metal surfaces like Cu(111), Cr(110), Ti(001), and oxygen-contaminated Cu(111), our results align closely with experimental observations, providing a practical and efficient approach for designing metallic or alloy substrates to achieve desired carbon nanostructures and explore further reaction possibilities.

Pilotins are mobile T3SS components involved in assembly and substrate specificity of the bacterial type III secretion system.

In animal pathogens, assembly of the type III secretion system injectisome requires the presence of so-called pilotins, small lipoproteins that assist the formation of the secretin ring in the outer membrane. Using a combination of functional assays, interaction studies, proteomics, and live-cell microscopy, we determined the contribution of the pilotin to the assembly, function, and substrate selectivity of the T3SS and identified potential new downstream roles of pilotin proteins. In absence of its pilotin SctG, Yersinia enterocolitica forms few, largely polar injectisome sorting platforms and needles. Accordingly, most export apparatus subcomplexes are mobile in these strains, suggesting the absence of fully assembled injectisomes. Remarkably, while absence of the pilotin all but prevents export of early T3SS substrates, such as the needle subunits, it has little effect on secretion of late T3SS substrates, including the virulence effectors. We found that although pilotins interact with other injectisome components such as the secretin in the outer membrane, they mostly localize in transient mobile clusters in the bacterial membrane. Together, these findings provide a new view on the role of pilotins in the assembly and function of type III secretion injectisomes.

Lasso Peptides: Exploring the Folding Landscape of Nature's Smallest Interlocked Motifs.

Lasso peptides make up a class of natural products characterized by a threaded structure. Given their small size and stability, chemical synthesis would offer tremendous potential for the development of novel therapeutics. However, the accessibility of the pre-folded lasso architecture has limited this advance. To better understand the folding process de novo, simulations are used herein to characterize the folding propensity of microcin J25 (MccJ25), a lasso peptide known for its antimicrobial properties. New algorithms are developed to unambiguously distinguish threaded from nonthreaded precursors and determine handedness, a key feature in natural lasso peptides. We find that MccJ25 indeed forms right-handed pre-lassos, in contrast to past predictions but consistent with all natural lasso peptides. Additionally, the native pre-lasso structure is shown to be metastable prior to ring formation but to readily transition to entropically favored unfolded and nonthreaded structures, suggesting that de novo lasso folding is rare. However, by altering the ring forming residues and appending thiol and thioester functionalities, we are able to increase the stability of pre-lasso conformations. Furthermore, conditions leading to protonation of a histidine imidazole side chain further stabilize the modified pre-lasso ensemble. This work highlights the use of computational methods to characterize lasso folding and demonstrates that de novo access to lasso structures can be facilitated by optimizing sequence, unnatural modifications, and reaction conditions like pH.

Pyrolytic decomposition of methanol, ethanol, and butanol at various temperatures and residence times in a high-temperature flow reactor

The potential use of low-carbon renewable fuel molecules, such as short chain alcohols, as a substitute or extender for fossil fuels, offers an opportunity to address pollutant emissions from transport and the sustainability of energy sources. Moreover, it may help reduce pollutants detrimental to air quality and human health, of which particulate matter (PM) is a significant contributor. To this end, the pyrolysis of three renewable alcohol fuels, methanol, ethanol, and butanol, has been studied in a laminar flow reactor at a sample inlet temperature range of 869 0C to 1120 0C. All the tested fuels were injected into a nitrogen carrier gas stream at a fixed concentration of 10,000 ppm on a carbon atom basis. A range of pyrolysis temperatures and residence times were selected so as to gain insight into the pyrolytic decomposition of short chain alcohol fuels to intermediate species important to the subsequent formation of benzene rings, larger polycyclic aromatic hydrocarbons (PAH), and particulate matter. In this paper, the presence of ten intermediary species that may aid in the formation of benzene rings and the growth of PAHs were quantified, with an emphasis on probable routes of first ring formation from the alcohols of varying chain length. Gaseous samples were collected from the pyrolyser at different temperatures and residence times using a novel high-temperature air-cooled ceramic sampling probe. The identification and quantification of intermediate gaseous species were undertaken by Gas Chromatography-Flame Ionization Detection (GC-FID). During methanol pyrolysis, only a tenth of the supplied carbon was detected as hydrocarbon gaseous species (mainly methane), with no benzene found, highlighting that methanol pyrolysis does not readily result in polyaromatic hydrocarbons and soot. Ethanol and butanol pyrolysis produced substantial amounts of ethylene and acetylene, suggesting a role in benzene and soot formation. Uniquely, pyrolysis of the longest chain alcohol, butanol, produced appreciable levels of C3 and C4 hydrocarbons, in addition to C1 and C2 hydrocarbons, suggesting additional reaction pathways for benzene formation and growth in comparison with ethanol.

Stability analysis of ring-like cavitation bubble cluster structure in standing wave field

Multi-cavitation bubble system can easily produce cavitation clouds with various structure types, including ring-like cavitation structures. Nonetheless, the evolutionary behavior of the structure and the physical mechanism of its formation are less investigated. In this work, high-speed photography and image analysis techniques are used to study the evolution of ring-like cavitation bubble aggregation structure in an ultrasonic cleaning tank with a frequency of 40 kHz. The ring-like structure usually appears near the pressure nodule, and its radius is less than a one-eighth wavelength. The structure involves establishment, stability and disappearance during an envelope wave period, and its morphology is stable. The ring-like cavitation structure exists as a bubble transport phenomenon, and the formed small bubble clusters flow to the outside of the ring and become discrete cavitation bubbles, or the bubble nuclei rejoin the cycle of bubble transport in the main accumulation area of the bubble. The size of the ring structure and the bubble accumulation area oscillate slightly, and there exists the whole structure rotation phenomenon, which depends on the interaction of the main sound field and the secondary radiation field with the bubbles. Furthermore, in this work, a mathematical model of two bubbles is used to investigate the physical mechanism behind the formation of a ring. It is found that the sound field is a key factor in ring formation. The ring chain model is used to analyze the structural stability by taking into account the time delay caused by the secondary acoustic radiation of the bubble. The numerical results show that the equivalent potential energy distribution of a ring bubble chain with a one-eighth wavelength in radius can stabilize each bubble in the potential well, and the radial distribution presents a ring-like barrier structure. The higher the sound pressure, the greater the equivalent potential, and the more the bubbles are clustered. The higher the driving sound field, the more complete the ring chain structure is. However, high sound pressure may cause the agglomeration of bubbles with high number density to disintegrate the stability of the ring aggregation of bubbles and evolve into other types of bubble aggregation structures. The theoretical results are in good consistence with the experimental phenomena.

Potent inhibitors targeting cyclin-dependent kinase 9 discovered via virtual high-throughput screening and absolute binding free energy calculations.

Due to the crucial regulatory mechanism of cyclin-dependent kinase 9 (CDK9) in mRNA transcription, the development of kinase inhibitors targeting CDK9 holds promise as a potential treatment strategy for cancer. A structure-based virtual screening approach has been employed for the discovery of potential novel CDK9 inhibitors. First, compounds with kinase inhibitor characteristics were identified from the ZINC15 database via virtual high-throughput screening. Next, the predicted binding modes were optimized by molecular dynamics simulations, followed by precise estimation of binding affinities using absolute binding free energy calculations based on the free energy perturbation scheme. The binding mode of molecule 006 underwent an inward-to-outward flipping, and the new binding mode exhibited binding affinity comparable to the small molecule T6Q in the crystal structure (PDB ID: 4BCF), highlighting the essential role of molecular dynamics simulation in capturing a plausible binding pose bridging docking and absolute binding free energy calculations. Finally, structural modifications based on these findings further enhanced the binding affinity with CDK9. The results revealed that enhancing the molecule's rigidity through ring formation, while maintaining the major interactions, reduced the entropy loss during the binding process and, thus, enhanced binding affinities.

Recent advances in [4 + 4] annulation of conjugated heterodienes with 1,4-dipolar species for the synthesis of eight-membered heterocycles.

Numerous eight-membered heterocycles are of significance in biological chemistry, the pharmaceutical industry, agrochemistry, and materials science. However, the assembly of eight-membered heterocycles is usually challenging due to the unfavorable enthalpic and entropic barriers of the transition states during the ring formation. Tremendous efforts have been devoted to the development of synthetic routes to eight-membered heterocycles. Despite these developments, the exploration of more strategies for the facile and effective assembly of eight-membered heterocyclic molecules in a single vessel under mild conditions is still highly desirable. The conjugated heterodiene-participating [4 + 4] annulation serves as a convenient and robust strategy for the synthesis of eight-membered heterocycles from easily accessible starting materials. In recent years, great progress has been achieved in this attractive field. In this short review, we highlighted the recent advances in the synthesis of eight-membered heterocycles via cascade reactions based on [4 + 4] annulation of conjugated heterodienes with 1,4-dipolar species. The brief backgrounds, the general reactions, the proposed mechanisms and their features are summarized. The prospects and challenges of this field are also outlined at the end of this review. In addition, to highlight the importance and practicality of these reactions, the properties of several series of eight-membered heterocycles have also been introduced briefly.

How does the blue ring form in a blue whirl: An experimental study

This paper presents an experimental study on the flame and flow structures of the blue whirl, in pursuit of an understanding of the blue ring's formation. The flame front was identified based on the OH* chemiluminescence signal and the flow field was obtained using high-frequency particle image velocimetry (PIV). The flame and flow field reveals the presence of a radial-inward boundary layer and the corner flow lifting the blue whirl. In the case of turbulent blue whirl, a discernible recirculation zone manifests within the flame, which offers direct evidence supporting the dominance of the vortex breakdown in blue whirl's formation. Furthermore, we find that the blue whirl's cone angle approximately equals the angle of the zero-vorticity line of the flow field, whereas the height of the blue ring aligns with the height of the upward deflection point on the radial-stagnation line. These findings demonstrate a strong coupling between the flame structures and the flow field. To understand the formation mechanism of the blue ring, the flow flux across the radial-stagnation line is calculated to estimate the equivalence ratio of the mixture forming the blue ring. It reveals that the blue ring is formed where the stoichiometric reaction occurs. This happens as the corner flow induces a strong shear to facilitate the mixing within the air-fuel mixture, causing the inner layer of the mixture to be diluted to the equivalence ratio of approximately 1 at the blue ring's location.

Formation of five-membered ring structures via reactions of o-benzyne

The formation of five-membered ring structures is important for the generation of curved and bowl-shaped polycyclic aromatic hydrocarbons (PAHs) under combustion conditions. Here, we report the identification of the indenyl (C9H7) radical – the simplest aromatic hydrocarbon radical carrying an adjacent five- and six-membered ring, as the major product of the o-benzyne (o-C6H4) reaction with propargyl (C3H3). Because real flames exhibit a complex chemistry, elucidation of a specific reaction is very challenging. Instead, we studied the o-C6H4 + C3H3 reaction in a resistively heated microtubular SiC reactor at controlled conditions of 1150 K and a pressure near 10–20 Torr. To this end, the reactants o-benzyne and propargyl were pyrolytically generated from benzoyl chloride and propargyl bromide. We identified the reactants and the indenyl radical isomer-selectively utilizing photoion mass-selected threshold photoelectron spectroscopy (ms-TPES). The experimentally observed predominant formation of indenyl radicals finally confirms the theoretical predictions of Matsugi and Miyoshi [Phys. Chem. Chem. Phys. 14 (2012), 9722–9728] and highlights a versatile route for the formation of five-membered rings and curved PAHs via reactions of o-benzyne that favor the formation of multiring species over aliphatically substituted aromatic species.

Antimicrobial peptide GL13K-Modified titanium in the epigenetic regulation of osteoclast differentiation via H3K27me3.

Implant surface designs have advanced to address challenges in oral rehabilitation for healthy and compromised bone. Several studies have analyzed the effects of altering material surfaces on osteogenic differentiation. However, the crucial role of osteoclasts in osseointegration has often been overlooked. Overactive osteoclasts can compromise implant stability. In this study, we employed a silanization method to alter pure titanium to produce a surface loaded with the antimicrobial peptide GL13K that enhanced biocompatibility. Pure titanium (Ti), silanization-modified titanium, and GL13K-modified titanium (GL13K-Ti) were co-cultured with macrophages. Our findings indicated that GL13K-Ti partially inhibited osteoclastogenesis and expression of osteoclast-related genes and proteins by limiting the formation of the actin ring, an important structure for osteoclast bone resorption. Our subsequent experiments confirmed the epigenetic role in regulating this process. GL13K-Ti was found to impact the degree of methylation modifications of H3K27 in the NFATc1 promoter region following RANKL-induced osteoclastic differentiation. In conclusion, our study unveils the potential mechanism of methylation modifications, a type of epigenetic regulatory modality, on osteoclastogenesis and activity on the surface of a material. This presents novel concepts and ideas for further broadening the clinical indications of oral implants and targeting the design of implant surfaces.

Beyond conventional Brønsted acid catalysis: leveraging the impact of charged moiety on the phenol for the construction of julolidine units

ETP demonstrated efficient catalytic activity for the formation of the julolidine ring. NMR and kinetic investigations showed the significant influence of the charged side arm on phenol over the rate of formation of the julolidine.

Accessing five- and seven-membered phosphorus-based heterocycles via cycloaddition reactions of azophosphines.

Heterocycles containing both phosphorus and nitrogen have seen increasing use in recent years in luminescent materials, coordination chemistry and as building blocks for inorganic polymers, yet their chemistry is currently dominated by five- and six-membered derivatives. Seven-membered P/N heterocycles are comparatively scarce and lack general, high yielding syntheses. Here, we explore the synthesis and characterisation of 1,2,5-diazaphosphepines from azophosphines. The mechanism has been probed in detail with both computational and experimental studies supporting a stepwise mechanism to form a five-membered ring, and subsequent ring expansion to the diazaphosphepine. Regioselective synthesis of five- and seven-membered rings is possible using asymmetric alkynes. The Lewis acidic borane B(C6F5)3 could either catalyse the formation of the seven-membered ring (iPr derivative) or trap out a key intermediate via a frustrated Lewis pair (FLP) mechanism (tBu derivative).

Frequency jump of a flickering buoyant jet diffusion flame influenced by ambient coflow

Flickering of laminar diffusion flames is known to be caused by the buoyancy-induced toroidal vortices attached to the outer flame surface, making a classical model for understanding flame-vortex interactions. This work experimentally investigates the impacts of ambient coflow on the flickering behaviors of a buoyant jet diffusion flame. Utilizing a simultaneous high-speed flame imaging/OH⁎ chemiluminescence imaging/particle image velocimetry measurement system, the evolutions and interactions of coherent flame and flow structures are resolved. The results demonstrate that the periodic deformation of the flame surface (i.e., flame flickering) arises from the periodic formation, growth, and shedding of the buoyancy-induced outer vortex rings (OVRs), manifesting as a hydrodynamic instability developing along the outer shear layer (OSL). Upon applying a weak-to-moderate coflow, the flame bulge's size gradually reduces, and the flickering frequency slightly increases with increasing coflow velocity. The notable frequency jump phenomenon is confirmed as the coflow velocity rises to a threshold value such that the flickering frequency undergoes a sudden increase of 3–4 Hz; this is also accompanied by a significant reduction in the flame bulge's size and a delay in flame pinch-off. Moreover, a second frequency jump of 2–3 Hz occurs at a higher coflow velocity. Based on quantitative analysis of the OVR core's evolution, we find that the frequency jumps result from a sudden downstream shift of the initial OVR core, essentially indicating the jump of the instability onset point of the OSL. From a hydrodynamic instability perspective, this phenomenon can be explained as a stabilization effect of the coflow on the OSL, resulting in the re-establishment of the instability condition in a downstream location.

Halogen bond catalysis of the [4+2] cycloaddition reaction of 2-alkenylindoles: catalytic modes and stereoselectivity.

Halogen bond donor catalysts have been widely used in organic reactions because they are environmentally friendly, inexpensive and recyclable. The [4+2] cycloaddition reaction is a key reaction in organic synthesis because of its ease of use, fast speed, and wide range of applications. In this work, halogen bond catalysis in the [4+2] cycloaddition reaction between 2-alkenylindoles was investigated based on DFT calculations. There are two modes of I⋯π halogen bond catalysis: either on the ethenyl of 2-alkenylindole (mode A) or on the five-membered ring of 2-alkenylindole (mode B). Both modes involve two steps: the formation of carbon-carbon bonds and the formation of six-membered rings. Gibbs free energy barriers were determined to investigate the stereoselectivity of the endo pathway and exo pathway. For mode A, the exo products were more easily generated when the substituent R = H, and the N-H⋯π interaction promoted high endo selectivity in the case of the substituent R = Ph. For mode B, an increasing proportion of endo products can be obtained in the order of catalyst I2, IBr and ICl. The π⋯π interaction of the substituent R = Ph promotes the [4+2] cycloaddition reaction, which is consistent with the experimental observation that R = Ph has a higher yield than R = H. The study of different catalytic modes and stereoselectivity would provide new ideas for the further study of the [4+2] cycloaddition reaction.

Identification of Klebsiella oxytoca by VITEK-2 System in Baghdad Hospitals

Background: Klebsiella oxytoca is a Gram-negative rod-shaped bacterium that is becoming resistant to multiple drugs and is frequently endangering patients' lives. It is a member of the human microbiota. Objectives: To assess the value of identifying K. oxytoca using an automated diagnostic system (VITEK-2) as compared to traditional manual methods. Materials and Methods: A total of 136 clinical specimens were collected from patients in Baghdad hospitals during a period from July to November 2022. VITEK-2 system was used to recognize the isolated bacteria to the genus and species level. The biochemical indole test was used as a confirmatory test at the species level. Results: K. oxytoca was more common in urine samples 49 (36.0%) followed by blood samples 21 (15.4%). Of the total collected samples 77 (56.6%) were from inpatients and (43.3%) were from outpatients. The primary identification by cultural and microscopic examinations diagnosed all the isolates as Klebsiella. VITEK-2 system recognized them as K. pneumoniae. The indole test confirmed the species as K. oxytoca by the formation of the red ring. Conclusion: using a simple biochemical test like indole is crucial in clinical laboratories to investigate the accuracy of bacterial identification at the species level. Continuous evaluation for the identification results of the automated systems is needed and can be done by updating the system software for the new emerging pathogens in the hospitals. Received June. 2022 Accepted Sept. 2023 Published Jan. 2024