Earth-abundant catalyst for modification of wheat straw to enhance ammonia mitigation from fertilized alkaline soil.

In this study, inexpensive earth-abundant catalyst of Co/TiO2 is coupled with a low-temperature modification approach to enhance NH3 adsorption capacity on wheat straw (WS). The highest NH3 uptake achieved is 111.9 mg/g, with 80.8 % retention even after 3 h of desorption. Mechanistic investigation indicates that the enhanced adsorption capacity stems from Co/TiO2, which facilitates generation of reactive oxygen species, leading improved ultra-micropore structure that enhances the interaction between NH3 and oxygen-containing functional groups through a trapping effect. The robust stability of adsorbed NH3 is attributed to the formation of amides or amines. Incorporation of only 1 wt% WS-Co to urea-fertilized alkaline soil reduced NH3 volatilization by 83.1 %. The significant effect is primarily attributed to the excellent adsorption capacity of WS-Co, rather than alterations in the relative abundance of the microbial community. These findings present a novel approach for development of effective fertiliser additive to mitigate NH3 volatilization from alkaline soil.

Effectiveness of masturbation Premature ejaculation diagnostic tool in diagnosing premature ejaculation in men without vaginal intercourse over the past six months: an observational study.

BACKGROUND: Premature ejaculation (PE) is a common concern for men and their partners, but current diagnostic tools mainly focus on men who have vaginal intercourse. The Masturbation Premature Ejaculation Diagnostic Tool (MPEDT) was created to address this gap, but its effectiveness for men who only engage in self-masturbation has not been studied. This research aimed to determine the frequency of self-reported PE patients who do not have vaginal intercourse and to evaluate the diagnostic accuracy of MPEDT for this group. METHOD: The study involved 446 male patients aged 18 to 40, and 40 non-self-reported-PE and non-vaginal-intercourse healthy males. Participants completed the MPEDT questionnaire and reported their recent six-months sex frequency. RESULT: Among the patients seeking treatment for PE, 21.75% had not engaged in vaginal intercourse in the past six months. Of the PE patients who completed the MPEDT questionnaire (86 patients), 90.7% were diagnosed with masturbatory-PE (MPE). The sensitivity for self-reported MPE and specificity for self-reported non-MPE were 93.02% and 72.5%, respectively. DISCUSSION: For patients who have not had vaginal intercourse in the past six months but engage in masturbation and seek treatment for PE, the PEDT may not effectively assess their ejaculatory function. The MPEDT, however, can effectively evaluate their ejaculatory function. This study also emphasizes the need for diagnostic tools tailored to this population.

Cinnamic Acid Derivatives: Recent Discoveries and Development Strategies for Alzheimer's Disease.

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder that leads to cognitive decline and memory impairment. It is characterized by the accumulation of Amyloid-beta (Aß) plaques, the abnormal phosphorylation of tau protein forming neurofibrillary tangles, and is often accompanied by neuroinflammation and oxidative stress, which contribute to neuronal loss and brain atrophy. At present, clinical anti-AD drugs are mostly single-target, improving the cognitive ability of AD patients, but failing to effectively slow down the progression of AD. Therefore, research on effective multi-target drugs for AD has become an urgent problem to address. The main derivatives of hydroxycinnamic acid, caffeic acid, and ferulic acid, are widely present in nature and have many pharmacological activities, such as antimicrobial, antioxidant, anti-inflammatory, neuroprotective, anti-Aß deposition, and so on. The occurrence and development of AD are often accompanied by pathologies, such as oxidative stress, neuroinflammation, and Aß deposition, suggesting that caffeic acid and ferulic acid can be used in the research on anti-AD drugs. Therefore, in this article, we have summarized the multi-target anti-AD derivatives based on caffeic acid and ferulic acid in recent years, and discussed the new design direction of cinnamic acid derivatives as backbone compounds. It is hoped that this review will provide some useful strategies for anti-AD drugs based on cinnamic acid derivatives.

Tetramethylpyrazine Nitrone (TBN) Reduces Amyloid ß Deposition in Alzheimer's Disease Models by Modulating APP Expression, BACE1 Activity, and Autophagy Pathways.

Alzheimer's disease (AD) is a neurodegenerative disorder associated with age. A wealth of evidence indicates that the amyloid ß (Aß) aggregates result from dyshomeostasis between Aß production and clearance, which plays a pivotal role in the pathogenesis of AD. Consequently, therapies targeting Aß reduction represent a promising strategy for AD intervention. Tetramethylpyrazine nitrone (TBN) is a novel tetramethylpyrazine derivative with potential for the treatment of AD. Previously, we demonstrated that TBN markedly enhanced cognitive functions and decreased the levels of Aß, APP, BACE 1, and hyperphosphorylated tau in 3×Tg-AD mice. However, the mechanism by which TBN inhibits Aß deposition is still unclear. In this study, we employed APP/PS1 mice treated with TBN (60 mg/kg, ig, bid) for six months, and N2a/APP695swe cells treated with TBN (300 µM) to explore the mechanism of TBN in Aß reduction. Our results indicate that TBN significantly alleviated cognitive impairment and reduced Aß deposition in APP/PS1 mice. Further investigation of the underlying mechanisms revealed that TBN decreased the expression of APP and BACE1, activated the AMPK/mTOR/ULK1 autophagy pathway, inhibited the PI3K/AKT/mTOR/ULK1 autophagy pathway, and decreased the phosphorylation levels of JNK and ERK in APP/PS1 mice. Moreover, TBN was found to significantly reduce the mRNA levels of APP and BACE1, as well as those of SP1, CTCF, TGF-ß, and NF-κB, transcription factors involved in regulating gene expression. Additionally, TBN was observed to decrease the level of miR-346 and increase the levels of miR-147 and miR-106a in the N2a/APP695swe cells. These findings indicate that TBN may reduce Aß levels likely by reducing APP expression by regulating APP gene transcriptional factors and miRNAs, reducing BACE1 expression, and promoting autophagy activities.

In situ chemical reprogramming of astrocytes into neurons: A new hope for the treatment of central neurodegenerative diseases?

Central neurodegenerative disorders (e.g. Alzheimer's disease (AD) and Parkinson's disease (PD)) are tightly associated with extensive neuron loss. Current therapeutic interventions merely mitigate the symptoms of these diseases, falling short of addressing the fundamental issue of neuron loss. Cell reprogramming, involving the transition of a cell from one gene expression profile to another, has made significant strides in the conversion between diverse somatic cell types. This advancement has been facilitated by gene editing techniques or the synergistic application of small molecules, enabling the conversion of glial cells into functional neurons. Despite this progress, the potential for in situ reprogramming of astrocytes in treating neurodegenerative disorders faces challenges such as immune rejection and genotoxicity. A novel avenue emerges through chemical reprogramming of astrocytes utilizing small molecules, circumventing genotoxic effects and unlocking substantial clinical utility. Recent studies have successfully demonstrated the in situ conversion of astrocytes into neurons using small molecules. Nonetheless, these findings have sparked debates, encompassing queries regarding the origin of newborn neurons, pivotal molecular targets, and alterations in metabolic pathways. This review succinctly delineates the background of astrocytes reprogramming, meticulously surveys the principal classes of small molecule combinations employed thus far, and examines the complex signaling pathways they activate. Finally, this article delves into the potential vistas awaiting exploration in the realm of astrocytes chemical reprogramming, heralding a promising future for advancing our understanding and treatment of neurodegenerative diseases.

Prussian blue analogue derived from leather waste as a bifunctional catalyst in zinc-air batteries.

A Prussian blue analogue was synthesized using biomass leather waste as a precursor by doping with Co2+ ions. This material, demonstrates good performance in both the oxygen reduction reaction and oxygen evolution reaction, and exhibits excellent charge-discharge performance and stability in zinc-air batteries.

Detection and application of hypochlorous acid in both aqueous environments and living organisms.

The scarcity of water resources has raised concerns regarding drinking water safety. Excessive addition of hypochlorous acid (OCl-) as a disinfectant in drinking water can result in severe consequences. Moreover, abnormal levels of OCl- within the human body can lead to various diseases. Employing fluorescence analysis, the design and synthesis of specific fluorescent probes for simultaneous detection of OCl- in water environments and living organisms holds strategic significance in ensuring the safety of drinking water and mitigating potential risks caused by its abnormal concentrations. This article utilizes naphthalimide as a precursor to develop a novel probe enabling highly sensitive detection of OCl- in water environments and at the organelle level within living organisms. This endeavor serves to provide assurance for drinking water safety and offers health alerts.

Mesopic pupil indices as potential risk factors for glare disability after intraocular implantable collamer lens implantation: prospective study.

PURPOSE: To explore the influence of preoperative factors, including varying pupil sizes and refractive attributes, on postoperative glare disability in patients undergoing implantable collamer lens (ICL) implantation. SETTING: Second Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China. DESIGN: Prospective observational study. METHODS: The preoperative ocular characteristics and 6-month postoperative glare status in eligible patients who underwent EVO-Visian ICL V4c (VICMO) implantation were analyzed. The glare disability criteria encompassed a glare symptom score >6 and glare sensitivity exceeding 1:2.7. Logistic regression analysis was used to explore the relationship between the preoperative ocular parameters and post-ICL glare. RESULTS: The study included 95 patients (mean age, 26.04 ± 6.29 years), comprising 30 men (58 eyes) and 65 women (129 eyes). Multivariate analysis revealed a significant correlation between postoperative glare disability and increased spherical power in preoperative mesopic pupils (ß = -0.124, P = .039), as well as elevated cylinder power in preoperative mesopic (ß = -0.412, P = .009) and photopic pupils (ß = -0.430, P = .007). Moreover, a larger preoperative mesopic pupil diameter (ß = 0.561, P = .005) demonstrated a significant correlation with glare disability. CONCLUSIONS: Preoperative mesopic pupil dimensions and associated refractive parameters, such as sphere and cylinder, were correlated with glare disability, including the cylinder aspect in photopic pupils, which can assist clinicians in optimizing preoperative selection for ICL implantation, aiding in the anticipation of potential glare disability risks.

Enhanced Directed Evolution in Mammalian Cells Yields a Hyperefficient Pyrrolysyl tRNA for Noncanonical Amino Acid Mutagenesis.

Heterologous tRNAs used for noncanonical amino acid (ncAA) mutagenesis in mammalian cells typically show poor activity. We recently introduced a virus-assisted directed evolution strategy (VADER) that can enrich improved tRNA mutants from naïve libraries in mammalian cells. However, VADER was limited to processing only a few thousand mutants; the inability to screen a larger sequence space precluded the identification of highly active variants with distal synergistic mutations. Here, we report VADER2.0, which can process significantly larger mutant libraries. It also employs a novel library design, which maintains base-pairing between distant residues in the stem regions, allowing us to pack a higher density of functional mutants within a fixed sequence space. VADER2.0 enabled simultaneous engineering of the entire acceptor stem of M. mazei pyrrolysyl tRNA (tRNAPyl ), leading to a remarkably improved variant, which facilitates more efficient incorporation of a wider range of ncAAs, and enables facile development of viral vectors and stable cell-lines for ncAA mutagenesis.

Clinical and Genetic Spectrum in a Large Cohort of Hereditary Spastic Paraplegia.

BACKGROUND: Next-generation sequencing-based molecular assessment has benefited the diagnosis of hereditary spastic paraplegia (HSP) subtypes. However, the clinical and genetic spectrum of HSP due to large fragment deletions/duplications has yet to be fully defined. OBJECTIVE: We aim to better characterize the clinical phenotypes and genetic features of HSP and to provide new thoughts on diagnosis. METHODS: Whole-exome sequencing (WES) was performed in patients with clinically suspected HSP, followed by multiple ligation-dependent probe amplification (MLPA) sequentially carried out for those with negative findings in known causative genes. Genotype-phenotype correlation analyses were conducted under specific genotypes. RESULTS: We made a genetic diagnosis in 60% (162/270) of patients, of whom 48.9% (132/270) had 24 various subtypes due to point mutations (SPG4/SPG11/SPG35/SPG7/SPG10/SPG5/SPG3A/SPG2/SPG76/SPG30/SPG6/SPG9A/SPG12/SPG15/SPG17/SPG18/SPG26/SPG49/SPG55/SPG56/SPG57/SPG62/SPG78/SPG80). Thirty patients were found to have causative rearrangements by MLPA (11.1%), among which SPG4 was the most prevalent (73.3%), followed by SPG3A (16.7%), SPG6 (3.3%), SPG7 (3.3%), and SPG11 (3.3%). Clinical analysis showed that some symptoms were often related to specific subtypes, and rearrangement-related SPG3A patients seemingly had later onset. We observed a presumptive anticipation among SPG4 and SPG3A families due to rearrangement. CONCLUSIONS: Based on the largest known Asian HSP cohort, including the largest subgroup of rearrangement-related pedigrees, we gain a comprehensive understanding of the clinical and genetic spectrum of HSP. We propose a diagnostic flowchart to sequentially detect the causative genes in practice. Large fragment mutations account for a considerable proportion of HSP, and thus, MLPA screening acts as a beneficial supplement to routine WES. © 2024 International Parkinson and Movement Disorder Society.

Early-onset familial essential tremor is associated with nucleotide expansions of spinocerebellar ataxia in China.

BACKGROUND: Essential tremor (ET) is a neurological disease characterized by action tremor in upper arms. Although its high heritability and prevalence worldwide, its etiology and association with other diseases are still unknown. METHOD: We investigated 10 common spinocerebellar ataxias (SCAs), including SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, SCA12, SCA17, SCA36, dentatorubral-pallidoluysian atrophy (DRPLA) in 92 early-onset familial ET pedigrees in China collected from 2016 to 2022. RESULT: We found one SCA12 proband carried 51 CAG repeats within PPP2R2B gene and one SCA3 proband with intermediate CAG repeats (55) with ATXN3 gene. The other 90 ET probands all had normal repeat expansions. CONCLUSION: Tremor can be the initial phenotype of certain SCA. For early-onset, familial ET patients, careful physical examinations are needed before genetic SCA screening.

Spastic paraplegia type 76 due to novel CAPN1 mutations: three case reports with literature review.

Spastic paraplegia type 76 (SPG76) is a subtype of hereditary spastic paraplegia (HSP) caused by calpain-1 (CAPN1) mutations. Our study described the phenotypic and genetic characteristics of three families with spastic ataxia due to various CAPN1 mutations and further explored the pathogenesis of the two novel mutations. The three patients were 48, 39, and 48 years old, respectively. Patients 1 and 3 were from consanguineous families, while patient 2 was sporadic. Physical examination showed hypertonia, hyperreflexia, and Babinski signs in the lower limbs. Patients 2 and 3 additionally had dysarthria and depression. CAPN1 mutations were identified by whole-exome sequencing, followed by Sanger sequencing and co-segregation analysis within the family. Functional examination of the newly identified mutations was further explored. Two homozygous mutations were detected in patient 1 (c.213dupG, p.D72Gfs*95) and patient 3 (c.1729+1G>A) with HSP, respectively. Patient 2 had compound heterozygous mutations c.853C>T (p.R285X) and c.1324G>A (p.G442S). Western blotting revealed the p.D72Gfs*95 with a smaller molecular weight than WT and p.G442S. In vitro, the wild-type calpain-1 is mostly located in the cytoplasm and colocalized with tubulin by immunostaining. However, p.D72Gfs*95 and p.G442S abnormally formed intracellular aggregation, with little colocalization with tubulin. In this study, we identified three cases with SPG76, due to four various CAPN1 mutations, presenting lower limb spasticity and ataxia, with or without bulbar involvement and emotional disorder. Among these, c.213dupG and c.1324G>A are first identified in this paper. The genotype-phenotype correlation of the SPG76 cases reported worldwide was further summarized.

Altitudinal variation in life-history features of a Qinghai-Tibetan Plateau lizard.

Environmental changes along an altitudinal gradient can facilitate the differentiation of life-history features in ectothermic species, but little attention has been devoted to the reciprocal influence of altitude and alpine slope directionality on life-history variation. According to life-history theory, increased environmental stress causes a change in reproductive allocation from number to quality of offspring, as well as a stronger trade-off between size and number of offspring. To clarify the influence of environmental pressures on the life-history features of the Qinghai toad-headed lizard Phrynocephalus vlangalii along an altitudinal cline, we surveyed late pregnant females from 3 populations of low (2,600 m), middle (3,400 m), and high (3,600 m) elevations in the Dangjin Mountain of Gansu, China from July to October 2019, and compared their inter-population differences in maternal body size, reproductive characteristics, offspring growth, and locomotor performance. Because of lower temperatures, higher humidity, and lower light intensity caused by slope aspect and altitude, the middle-altitude region experienced stronger environmental stress than the high- and low-altitude regions. Our results showed that females were larger at middle- and high-altitude sites and smaller at the low-altitude site, following Bergmann's rule. We also found that females from low-altitude population gave birth earlier than those from the middle and high altitudes. Our results showed a shift in the offspring size-number trade-off of P. vlangalii in response to colder and harsher environments, with lizards from the alpine steppe (i.e. the middle- and high-altitude habitats) producing fewer but larger offspring than those from the warm steppe (i.e. the low-altitude habitat). Low-altitude juveniles grew faster than high-altitude ones, but at the same rates as middle-altitude juveniles. This result demonstrates that the growth of P. vlangalii was associated with temperature and light intensity. Our findings contribute to enhancing our understanding of the altitudinal variation in life-history features of plateau ectotherms and their phenotypic plasticity or local adaptation.

Glycopolypeptide hydrogels with adjustable enzyme-triggered degradation: A novel proteoglycans analogue to repair articular-cartilage defects.

Proteoglycans (PGs), also known as a viscous lubricant, is the main component of the cartilage extracellular matrix (ECM). The loss of PGs is accompanied by the chronic degeneration of cartilage tissue, which is an irreversible degeneration process that eventually develops into osteoarthritis (OA). Unfortunately, there is still no substitute for PGs in clinical treatments. Herein, we propose a new PGs analogue. The Glycopolypeptide hydrogels in the experimental groups with different concentrations were prepared by Schiff base reaction (Gel-1, Gel-2, Gel-3, Gel-4, Gel-5 and Gel-6). They have good biocompatibility and adjustable enzyme-triggered degradability. The hydrogels have a loose and porous structure suitable for the proliferation, adhesion, and migration of chondrocytes, good anti-swelling, and reduce the reactive oxygen species (ROS) in chondrocytes. In vitro experiments confirmed that the glycopolypeptide hydrogels significantly promoted ECM deposition and up-regulated the expression of cartilage-specific genes, such as type-II collagen, aggrecan, and glycosaminoglycans (sGAG). In vivo, the New Zealand rabbit knee articular cartilage defect model was established and the hydrogels were implanted to repair it, the results showed good cartilage regeneration potential. It is worth noting that the Gel-3 group, with a pore size of 122 â€‹± â€‹12 â€‹µm, was particularly prominent in the above experiments, and provides a theoretical reference for the design of cartilage-tissue regeneration materials in the future.

Trends in Prevalence and Disability-Adjusted Life-Years of Alzheimer's Disease and Other Dementias in China from 1990 to 2019.

INTRODUCTION: China has the largest population of people with dementia in the world and is estimated to have approximately a quarter of the entire population with dementia worldwide, bringing a heavy burden on the public and healthcare systems. We aimed to analyze the burden of Alzheimer's disease and other dementias in China over the past three decades. METHODS: The data on disease burden owing to Alzheimer's disease and other dementias in China from 1990 to 2019 were extracted from the Global Burden of Disease (GBD) 2019 datasets. The estimated annual percentage changes (EAPCs) were calculated to assess the temporal trends, and the ratio of years lived with disability (YLDs) to disability-adjusted life-years (DALYs) was used as an indicator to evaluate the healthcare system. RESULT: In China, the overall age-standardized rates (ASRs) of the prevalence and DALYs of Alzheimer's disease and other dementias increased from 1990 to 2019, and their EAPCs were 0.66 (95% confidence interval [CI], 0.57-0.75) and 0.26 (95% CI, 0.21-0.31), respectively. ASRs and the total number of dementia in females remained higher than in males, but the upward trend in ASRs among men was more pronounced than in women. The female-to-male ratio of the age-standardized DALY rate peaked in the 75-79 year age group in 2019 (female-to-male ratio of 1.32). The YLDs:DALYs ratio in China experienced a gradual increase and finally stayed above the global average since 2011. CONCLUSION: China has experienced a remarkably rising burden of dementia over the past three decades. The more significant burden of dementia was in females, but the potentially increasing burden of dementia in males cannot be underestimated.

Challenges and optimal strategies of CAR T therapy for hematological malignancies.

ABSTRACT: Remarkable improvement relative to traditional approaches in the treatment of hematological malignancies by chimeric antigen receptor (CAR) T-cell therapy has promoted sequential approvals of eight commercial CAR T products within last 5 years. Although CAR T cells' productization is now rapidly boosting their extensive clinical application in real-world patients, the limitation of their clinical efficacy and related toxicities inspire further optimization of CAR structure and substantial development of innovative trials in various scenarios. Herein, we first summarized the current status and major progress in CAR T therapy for hematological malignancies, then described crucial factors which possibly compromise the clinical efficacies of CAR T cells, such as CAR T cell exhaustion and loss of antigen, and finally, we discussed the potential optimization strategies to tackle the challenges in the field of CAR T therapy.

PLP1 gene mutations cause spastic paraplegia type 2 in three families.

OBJECTIVE: Spastic paraplegia type 2 (SPG2) is an X-linked recessive (XLR) form of hereditary spastic paraplegia (HSP) caused by mutations in proteolipid protein 1 (PLP1) gene. We described the clinical and genetic features of three unrelated families with PLP1 mutations and reviewed PLP1-related cases worldwide to summarize the genotype-phenotype correlations. METHODS: The three probands were 23, 26, and 27 years old, respectively, with progressively aggravated walking difficulty as well as lower limb spasticity. Detailed physical examination showed elevated muscle tone, hyperreflexia, and Babinski signs in lower limbs. Brain MRI examinations were investigated for all cases. PLP1 mutations were identified by whole exome sequencing, followed by Sanger sequencing, family co-segregation, and phenotypic reevaluation. RESULTS: A total of eight patients with SPG2 were identified in these three families. The probands additionally had cognitive impairment, urinary or fecal incontinence, ataxia, and white matter lesions (WML) in periventricular regions, with or without kinetic tremor. Three hemizygous mutations in PLP1 were identified, including c.453+159G>A, c.834A>T (p.*278C), and c.434G>A (p.W145*), of which c.834A>T was first associated with HSP. INTERPRETATION: We identified three families with complicated SPG2 due to three PLP1 mutations. Our study supports the clinically inter-and intra-family heterogeneity of SPG2. The periventricular region WML and cognitive impairment are the most common characteristics. The kinetic tremor in upper limbs was observed in 2/3 families, suggesting the spectrum of PLP1-related disorders is still expanding.

Virus-assisted directed evolution of enhanced suppressor tRNAs in mammalian cells.

Site-specific incorporation of unnatural amino acids (Uaas) in living cells relies on engineered aminoacyl-transfer RNA synthetase-tRNA pairs borrowed from a distant domain of life. Such heterologous suppressor tRNAs often have poor intrinsic activity, presumably due to suboptimal interaction with a non-native translation system. This limitation can be addressed in Escherichia coli using directed evolution. However, no suitable selection system is currently available to do the same in mammalian cells. Here we report virus-assisted directed evolution of tRNAs (VADER) in mammalian cells, which uses a double-sieve selection scheme to facilitate single-step enrichment of active yet orthogonal tRNA mutants from naive libraries. Using VADER we developed improved mutants of Methanosarcina mazei pyrrolysyl-tRNA, as well as a bacterial tyrosyl-tRNA. We also show that the higher activity of the most efficient mutant pyrrolysyl-tRNA is specific for mammalian cells, alluding to an improved interaction with the unique mammalian translation apparatus.

Burden of Parkinson Disease in China, 1990-2019: Findings from the 2019 Global Burden of Disease Study.

INTRODUCTION: China has the most people with Parkinson disease (PD) in the world and is estimated to have over half of the worldwide PD population. The objective of this study was to analyze the corresponding burden of PD in China for the past decades. METHOD: Data on disease burden related to PD in China were retrieved from the Global Burden of Disease (GBD) 2019 study. The estimated annual percentage changes (EAPCs) were calculated to assess temporal trends, and the ratio of years lived with disability (YLDs) to disability-adjusted life years (DALYs) was used as an index to evaluate the healthcare system. RESULT: Nationally, the burden of PD increased from 1990 to 2019. Although the age-standardized incidence rate (ASIR) increased, the age-standardized death rate (ASDR) and age-standardized DALY rate both decreased. Age-standardized rates of PD in males remained higher than those in females, but trends in ASDR and the age-standardized DALY rate for females showed a pronounced decrease. The most remarkable increase in the ASIR was in individuals aged 45-49 years, with an EAPC of 1.74 (95% confidence interval, 1.26-2.21). The YLDs:DALYs ratio continuously increased compared with global figures and even with countries with high sociodemographic index (SDI). CONCLUSION: Although ASDR and age-standardized DALY rates for PD have been declining, the burden of PD still needs attention as the total numbers have increased over the period. Generally, the greater burden of PD was in males. A sound health system with services tailored to PD continues to be required in the future.