Exploring Temporomandibular Disorders (TMDs) and Occlusion Debate in Dentistry: Biting Into Controversy.

Some conditions known as temporomandibular disorders (TMDs) affect surrounding muscles and jaw joints. In dentistry, there has been discussion and research on the connection between TMDs and occlusion, which is how the upper and lower teeth meet. Although some dental experts have proposed a direct link between TMDs and occlusion, the specifics of this relationship are still unclear and have many facets. More particularly, the research facets of "occlusion" remain one of the most contentious subjects in TMDs. This abstract aims to provide an overview of TMDs and occlusion, summarizing the key points from the literature. The etiological factors contributing to the TMDs, including occlusal, psychological, and hormonal factors, are also analyzed. The second part of the article includes the concept of malocclusion, emphasizing its significance in masticatory function and overall health. Anterior open and posterior open bites and the potential influence of occlusal factors on TMDs are elucidated.

Evaluation of the Influence of Nasolabial Angle, Upper Sulcus Depth, and Nasal Tip Protrusion in the Perception of Facial Attractiveness.

Objective: To evaluate the influence of variations in the upper sulcus depth, nasal tip protrusion, and nasolabial angle on the esthetic perception of profiles. Design: A web-based survey study and was conducted in the Department of Orthodontics and Dentofacial Orthopaedics. This survey was conducted for a period of 10 months and included orthodontists practicing in India. Methods: This study included lateral cephalograms of the most esthetic profiles from a set of 30 profiles that were within Holdaways norms; the most esthetic profile was determined by a panel of two orthodontists and two general dentists. The most esthetic profile photograph will be transferred to a computer in Corel software. The outline of the profile will remain the same, with the inner aspect converted into a dark area (black); now, the profile is completely converted into facial silhouettes. This black facial silhouette is presented to avoid any distractions and bias. There will be a total of 27 silhouettes by various combinations of increased, decreased, and normal values for nasolabial angle, upper sulcus depth, and nasal tip protrusions. Results: Both the orthodontist and layman chose the most favored profile as a normal profile having a normal nasal tip, normal nasolabial angle, and normal upper sulcus depth, whereas among dentists, 50% chose the most favored profile in which the nasolabial angle was normal but the nasal tip and upper labial sulcus were decreased. When it comes to the least favored profiles, opinions varied between orthodontists, dentists, and laymen. Conclusion: The perception of facial esthetics has always been and still is varied between the layman, the dentist, and the orthodontists. Profiles with normal to sharp noses with normal and increased nasolabial angles were considered more attractive than the others. Profiles with fuller upper labial sulci were considered least attractive with other parameters changing.

ELONGATED HYPOCOTYL 5 regulates BRUTUS and affects iron acquisition and homeostasis in Arabidopsis thaliana.

Iron (Fe) is an essential micronutrient for both plants and animals. Fe-limitation significantly reduces crop yield and adversely impacts on human nutrition. Owing to limited bioavailability of Fe in soil, plants have adapted different strategies that not only regulate Fe-uptake and homeostasis but also bring modifications in root system architecture to enhance survival. Understanding the molecular mechanism underlying the root growth responses will have critical implications for plant breeding. Fe-uptake is regulated by a cascade of basic helix-loop-helix (bHLH) transcription factors (TFs) in plants. In this study, we report that HY5 (Elongated Hypocotyl 5), a member of the basic leucine zipper (bZIP) family of TFs, plays an important role in the Fe-deficiency signaling pathway in Arabidopsis thaliana. The hy5 mutant failed to mount optimum Fe-deficiency responses, and displayed root growth defects under Fe-limitation. Our analysis revealed that the induction of the genes involved in Fe-uptake pathway (FIT-FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION FACTOR, FRO2-FERRIC REDUCTION OXIDASE 2 and IRT1-IRON-REGULATED TRANSPORTER1) is reduced in the hy5 mutant as compared with the wild-type plants under Fe-deficiency. Moreover, we also found that the expression of coumarin biosynthesis genes is affected in the hy5 mutant under Fe-deficiency. Our results also showed that HY5 negatively regulates BRUTUS (BTS) and POPEYE (PYE). Chromatin immunoprecipitation followed by quantitative polymerase chain reaction revealed direct binding of HY5 to the promoters of BTS, FRO2 and PYE. Altogether, our results showed that HY5 plays an important role in the regulation of Fe-deficiency responses in Arabidopsis.

An Efficient Approach for SARS-CoV-2 Monoclonal Antibody Production via Modified mRNA-LNP Immunization

Throughout the COVID-19 pandemic, many prophylactic and therapeutic drugs have been evaluated and introduced. Among these treatments, monoclonal antibodies (mAbs) that bind to and neutralize SARS-CoV-2 virus have been applied as complementary and alternative treatments to vaccines. Although different methodologies have been utilized to produce mAbs, traditional hybridoma fusion technology is still commonly used for this purpose due to its unmatched performance record. In this study, we coupled the hybridoma fusion strategy with mRNA-lipid nanoparticle (LNP) immunization. This time-saving approach can circumvent biological and technical hurdles, such as difficult to express membrane proteins, antigen instability, and the lack of posttranslational modifications on recombinant antigens. We used mRNA-LNP immunization and hybridoma fusion technology to generate mAbs against the receptor binding domain (RBD) of SARS-CoV-2 spike (S) protein. Compared with traditional protein-based immunization approaches, inoculation of mice with RBD mRNA-LNP induced higher titers of serum antibodies. In addition, the mAbs we obtained can bind to SARS-CoV-2 RBDs from several variants. Notably, RBD-mAb-3 displayed particularly high binding affinities and neutralizing potencies against both Alpha and Delta variants. In addition to introducing specific mAbs against SARS-CoV-2, our data generally demonstrate that mRNA-LNP immunization may be useful to quickly generate highly functional mAbs against emerging infectious diseases.

Broadly neutralizing antibodies against Omicron variants of SARS-CoV-2 derived from mRNA-lipid nanoparticle-immunized mice

The COVID-19 pandemic continues to threaten human health worldwide, as new variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged. Currently, the predominant circulating strains around the world are Omicron variants, which can evade many therapeutic antibodies. Thus, the development of new broadly neutralizing antibodies remains an urgent need. In this work, we address this need by using the mRNA-lipid nanoparticle immunization method to generate a set of Omicron-targeting monoclonal antibodies. Five of our novel K-RBD-mAbs show strong binding and neutralizing activities toward all SARS-CoV-2 variants of concern (Alpha, Beta, Gamma, Delta and Omicron). Notably, the epitopes of these five K-RBD-mAbs are overlapping and localized around K417 and F486 of the spike protein receptor binding domain (RBD). Chimeric derivatives of the five antibodies (K-RBD-chAbs) neutralize Omicron sublineages BA.1 and BA.2 with low IC50 values that range from 5.7 to 12.9 ng/mL. Additionally, we performed antibody humanization on a broadly neutralizing chimeric antibody to create K-RBD-hAb-62, which still retains excellent neutralizing activity against Omicron. Our results collectively suggest that these five therapeutic antibodies may effectively combat current and emerging SARS-CoV-2 variants, including Omicron BA.1 and BA.2. Therefore, the antibodies can potentially be used as universal neutralizing antibodies against SARS-CoV-2.

Omicron-specific mRNA vaccine induced potent neutralizing antibody against Omicron but not other SARS-CoV-2 variants

The emerging SARS-CoV-2 variants of concern (VOC) harbor mutations associated with increasing transmission and immune escape, hence undermine the effectiveness of current COVID-19 vaccines. In late November of 2021, the Omicron (B.1.1.529) variant was identified in South Africa and rapidly spread across the globe. It was shown to exhibit significant resistance to neutralization by serum not only from convalescent patients, but also from individuals receiving currently used COVID-19 vaccines with multiple booster shots. Therefore, there is an urgent need to develop next generation vaccines against VOCs like Omicron. In this study, we develop a panel of mRNA-LNP-based vaccines using the receptor binding domain (RBD) of Omicron and Delta variants, which are dominant in the current wave of COVID-19. In addition to the Omicron- and Delta-specific vaccines, the panel also includes a "Hybrid" vaccine that uses the RBD containing all 16 point-mutations shown in Omicron and Delta RBD, as well as a bivalent vaccine composed of both Omicron and Delta RBD-LNP in half dose. Interestingly, both Omicron-specific and Hybrid RBD-LNP elicited extremely high titer of neutralizing antibody against Omicron itself, but few to none neutralizing antibody against other SARS-CoV-2 variants. The bivalent RBD-LNP, on the other hand, generated antibody with broadly neutralizing activity against the wild-type virus and all variants. Surprisingly, similar cross-protection was also shown by the Delta-specific RBD-LNP. Taken together, our data demonstrated that Omicron-specific mRNA vaccine can induce potent neutralizing antibody response against Omicron, but the inclusion of epitopes from other variants may be required for eliciting cross-protection. This study would lay a foundation for rational development of the next generation vaccines against SARS-CoV-2 VOCs.